An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45.
5-Fluoro-2'-deoxyuridylate. An inhibitor of thymidylate synthetase. Formed from 5-fluorouracil or 5-fluorodeoxyuridine.
Uracil nucleotides which contain deoxyribose as the sugar moiety.
5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety.
Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)
An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.
Antimetabolites that are useful in cancer chemotherapy.
An oxidoreductase involved in pyrimidine base degradation. It catalyzes the catabolism of THYMINE; URACIL and the chemotherapeutic drug, 5-FLUOROURACIL.
Thiophenes are aromatic heterocyclic organic compounds containing a five-membered ring with four carbon atoms and one sulfur atom, which are found in various natural substances and synthesized for use in pharmaceuticals and agrochemicals.
Compounds based on 5,6,7,8-tetrahydrofolate.
A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.
Quinazolines are heterocyclic aromatic organic compounds consisting of a benzene ring fused to a pyrazine ring, which are synthesized and used as intermediates in pharmaceuticals, particularly in the production of various drugs such as antimalarials, antihypertensives, and antitumor agents.
An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.4.
Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.
A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against PNEUMOCYSTIS PNEUMONIA in AIDS patients. Myelosuppression is its dose-limiting toxic effect.
2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies.
A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.
A rod-shaped bacterium isolated from milk and cheese, dairy products and dairy environments, sour dough, cow dung, silage, and human mouth, human intestinal contents and stools, and the human vagina.
An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.
Derivatives of folic acid (pteroylglutamic acid). In gamma-glutamyl linkage they are found in many tissues. They are converted to folic acid by the action of pteroylpolyglutamate hydrolase or synthesized from folic acid by the action of folate polyglutamate synthetase. Synthetic pteroylpolyglutamic acids, which are in alpha-glutamyl linkage, are active in bacterial growth assays.
Leukemia L1210 is a designation for a specific murine (mouse) leukemia cell line that was originally isolated from a female mouse with an induced acute myeloid leukemia, which is widely used as a model in cancer research, particularly for in vivo studies of drug efficacy and resistance.
A peptide that is a homopolymer of glutamic acid.
A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.
An enzyme that catalyzes the transfer of 2-deoxy-D-ribose from THYMIDINE to orthophosphate, thereby liberating thymidine.
An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.
Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154)
Thymidine is a pyrimidine nucleoside, consisting of a thymine base linked to a deoxyribose sugar by a β-N1-glycosidic bond, which plays a crucial role in DNA replication and repair processes as one of the four nucleosides in DNA.
The active metabolite of FOLIC ACID. Leucovorin is used principally as an antidote to FOLIC ACID ANTAGONISTS.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A pyridoxal phosphate enzyme that catalyzes the reaction of glycine and 5,10-methylene-tetrahydrofolate to form serine. It also catalyzes the reaction of glycine with acetaldehyde to form L-threonine. EC 2.1.2.1.
Enzymes that catalyze the transfer of hydroxymethyl or formyl groups. EC 2.1.2.
The enzyme catalyzing the formation of orotidine-5'-phosphoric acid (orotidylic acid) from orotic acid and 5-phosphoribosyl-1-pyrophosphate in the course of pyrimidine nucleotide biosynthesis. EC 2.4.2.10.
Tumors or cancer of the COLON.
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
Enzyme that catalyzes the first step of the tricarboxylic acid cycle (CITRIC ACID CYCLE). It catalyzes the reaction of oxaloacetate and acetyl CoA to form citrate and coenzyme A. This enzyme was formerly listed as EC 4.1.3.7.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A ubiquitously expressed folic acid transporter that functions via an antiporter mechanism which is coupled to the transport of organic phosphates.
The rate dynamics in chemical or physical systems.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Polysaccharide isolated from the edible mushroom LENTINULA EDODES. The exact composition is unknown.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
Guanine is a purine nucleobase, one of the four nucleobases in the nucleic acid of DNA and RNA, involved in forming hydrogen bonds between complementary base pairs in double-stranded DNA molecules.
An enzyme that catalyzes the formation of methionine by transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine. It requires a cobamide coenzyme. The enzyme can act on mono- or triglutamate derivatives. EC 2.1.1.13.
An enzyme that catalyzes the conversion of aminoimidazole-4-carboxamide ribonucleotide to 5-formyl-aminoimidazole-4-carboxamide ribonucleotide in the purine de novo synthesis pathway. It requires the cofactor N(10)-FORMYLTETRAHYDROFOLATE as the formyl donor.
A flavoprotein amine oxidoreductase that catalyzes the reversible conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. This enzyme was formerly classified as EC 1.1.1.171.
An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11.
An enzyme that catalyzes the transfer of a formyl group from N10-formyltetrahydrofolate to N1-(5-phospho-D-ribosyl)glycinamide to yield N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide and tetrahydrofolate. It plays a role in the de novo purine biosynthetic pathway.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.
Uracil is a nitrogenous base, specifically a pyrimidine derivative, which constitutes one of the four nucleobases in the nucleic acid of RNA (ribonucleic acid), pairing with adenine via hydrogen bonds during base-pairing. (25 words)
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.
Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (INVERTED TANDEM REPEATS).
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Derivatives of the dimethylisoalloxazine (7,8-dimethylbenzo[g]pteridine-2,4(3H,10H)-dione) skeleton. Flavin derivatives serve an electron transfer function as ENZYME COFACTORS in FLAVOPROTEINS.
Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups.
Cell surface receptors that bind to and transport FOLIC ACID, 5-methyltetrahydrofolate, and a variety of folic acid derivatives. The receptors are essential for normal NEURAL TUBE development and transport folic acid via receptor-mediated endocytosis.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
An enzyme that catalyzes the hydrolytic deamination of deoxycytidylic acid to deoxyuridylic acid and ammonia. It plays an important role in the regulation of the pool of deoxynucleotides in higher organisms. The enzyme also acts on some 5-substituted deoxycytidylic acids. EC 3.5.4.12.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A subtype of GPI-anchored folate receptors that is expressed in tissues of epithelial origin. This protein is also identified as an ovarian-tumor-specific antigen.
An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Established cell cultures that have the potential to propagate indefinitely.
The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A malignant epithelial tumor with a glandular organization.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.

Persistent induction of apoptosis and suppression of mitosis as the basis for curative therapy with S-1, an oral 5-fluorouracil prodrug in a colorectal tumor model. (1/1176)

In an effort to improve the therapeutic selectivity of 5-fluorouracil (FUra) against colorectal cancer, S-1, a combination agent including a prodrug of FUra with two modulators, was recently developed by Taiho Pharmaceuticals Co. S-1 is a combination of tegafur (FT), 5-chloro-2,4-hydroxypyridine, and potassium oxonate in the molar ratio of 1.0:0.4:1.0, with the latter two components as inhibitors of dihydropyrimidine dehydrogenase and phosphoribosylpyrophosphate transferase, respectively. In this study, the therapeutic selectivity and efficacy of S-1 (oral) was compared with FT (oral) and FUra (i.v. infusion) in rats bearing advanced colorectal cancer by using clinically relevant schedules. The maximum tolerated doses (MTDs) of S-1, FT, and FUra were 31.5, 200, and 25 mg/kg/d for 7 days and 22.5, 150, and 12.5 mg/kg/d for 28 days, respectively. The therapeutic index of S-1 was 4- to 5-fold higher than that of either FT or FUra. S-1 achieved 100% complete tumor regression (CR) at its MTD in both 7-day and 28-day schedules. Furthermore, the high incidences of stomatitis, alopecia, and diarrhea observed with FUra and FT, were not observed with S-1. In an attempt to understand the basis for the observed superior therapeutic selectivity with S-1, we studied pharmacokinetic analysis of FUra, drug-induced apoptosis, suppression of mitosis, and inhibition of thymidylate synthase (TS) after S-1, FUra, or FT administration. The peak plasma FUra concentrations derived from FUra or S-1 (FT) at comparable MTDs were similar, but the plasma level of FUra was higher with S-1 than with FUra. Induction of high and sustained apoptosis was achieved with S-1. Although the initial level of apoptosis induced by FUra was comparable to S-1, it was not sustained. The sustained level of apoptosis appears to correlate with tumor growth inhibition. Mitotic figures were more greatly suppressed with S-1 treatment than with FUra. Studies on TS inhibition indicated that, although both S-1 and FUra caused a 4- to 6-fold induction of total TS protein, single oral administration of S-1 was superior to 24-h infusion of FUra in suppressing free TS. The data are consistent with the observation that the therapeutic efficacy of S-1 (100% cure) over FUra is associated with high and sustained levels of drug-induced apoptosis, greater suppression of mitosis, and inhibition of free TS in tumor tissues.  (+info)

Colorectal liver metastasis thymidylate synthase staining correlates with response to hepatic arterial floxuridine. (2/1176)

We assessed whether intensity of colorectal liver metastasis staining with the thymidylate synthase (TS) antibody TS106 predicted response to hepatic arterial infusion (HAI) of floxuridine chemotherapy. Liver metastasis biopsies were taken during laparotomy for hepatic arterial cannulation and stained using the TS106 monoclonal antibody. Staining intensity was designated at histological examination by two independent assessors as either "high" or "low." Patients were treated by HAI, and liver metastasis response was assessed by comparison of computed tomography scan tumor volume before and after 4 months of treatment. A significant correlation (Fisher's exact test, P = 0.01) was noted between partial response to HAI and TS106 staining intensity in patients with colorectal liver metastases. Seventy-five percent of patients with evidence of a partial response had low TS staining compared with 29% of nonresponders. There was a significant difference (Fisher's exact test, P = 0.01) in the proportion of low (9 of 16) compared with high (3 of 20) TS staining tumors in which a partial response occurred. There was no significant difference (logrank test, P = 0.4) in survival from hepatic cannulation and HAI treatment of high (median, 322 days; interquartile range, 236-411) compared with low (median, 335 days; interquartile range, 301-547) TS staining patients. This study demonstrates an inverse correlation between TS immunohistochemical staining intensity in colorectal liver metastases and response to HAI. The results suggest that a prospective assessment of TS staining intensity in colorectal liver metastases would be useful to determine whether this method can be used to define patients who will benefit from HAI chemotherapy.  (+info)

Suppression of replication of multidrug-resistant HIV type 1 variants by combinations of thymidylate synthase inhibitors with zidovudine or stavudine. (3/1176)

The replication of recombinant multidrug-resistant HIV-1 clones modeled on clinically derived resistant HIV-1 strains from patients receiving long-term combination therapy with zidovudine (AZT) plus 2',3'-dideoxycytidine was found to regain sensitivity to AZT and stavudine (D4T) as a consequence of a pharmacologically induced decrease in de novo dTMP synthesis. The host-cell system used was phytohemagglutinin-stimulated peripheral blood mononuclear cells; dTMP and dTTP depletion were induced by single exposures to a low level of the thymidylate synthase inhibitor 5-fluorouracil (5-FU) or its deoxynucleoside, 2'-deoxy-5-fluorouridine. The host-cell response to the latter was biphasic: a very rapid decrease in the rate of de novo dTMP formation and, consequently, in intracellular dTTP pools, followed by slower recovery in both indices over 3 to 24 h. With the additional presence of AZT or D4T, however, replication of the multidrug-resistant HIV-1 strains remained inhibited, indicating dependence of HIV DNA chain termination by AZT-5'-monophosphate or 2',3'-didehydro-2', 3'-dideoxythymidine-5'-monophosphate in these resistant strains on simultaneous inhibition of host-cell de novo synthesis of thymidine nucleotides. No effect on viability of control (uninfected) phytohemagglutinin-stimulated/peripheral blood mononuclear cells was noted on 6-day exposures to 5-FU or 2'-deoxy-5-fluorouridine alone or in combination with AZT or D4T, even at drug levels severalfold higher than those used in the viral inhibition studies. These studies may provide useful information for the potential clinical use of AZT/5-FU or D4T/5-FU combinations for the prevention or reversal of multidrug resistance associated with long-term dideoxynucleoside combination therapy.  (+info)

Crystal structure of deoxycytidylate hydroxymethylase from bacteriophage T4, a component of the deoxyribonucleoside triphosphate-synthesizing complex. (4/1176)

Bacteriophage T4 deoxycytidylate hydroxymethylase (EC 2.1.2.8), a homodimer of 246-residue subunits, catalyzes hydroxymethylation of the cytosine base in deoxycytidylate (dCMP) to produce 5-hydroxymethyl-dCMP. It forms part of a phage DNA protection system and appears to function in vivo as a component of a multienzyme complex called deoxyribonucleoside triphosphate (dNTP) synthetase. We have determined its crystal structure in the presence of the substrate dCMP at 1.6 A resolution. The structure reveals a subunit fold and a dimerization pattern in common with thymidylate synthases, despite low (approximately 20%) sequence identity. Among the residues that form the dCMP binding site, those interacting with the sugar and phosphate are arranged in a configuration similar to the deoxyuridylate binding site of thymidylate synthases. However, the residues interacting directly or indirectly with the cytosine base show a more divergent structure and the presumed folate cofactor binding site is more open. Our structure reveals a water molecule properly positioned near C-6 of cytosine to add to the C-7 methylene intermediate during the last step of hydroxymethylation. On the basis of sequence comparison and crystal packing analysis, a hypothetical model for the interaction between T4 deoxycytidylate hydroxymethylase and T4 thymidylate synthase in the dNTP-synthesizing complex has been built.  (+info)

Impact of 9-(2-phosphonylmethoxyethyl)adenine on (deoxy)ribonucleotide metabolism and nucleic acid synthesis in tumor cells. (5/1176)

Following exposure to 9-(2-phosphonylmethoxyethyl)adenine (an inhibitor of the cellular DNA polymerases alpha, delta and epsilon), human erythroleukemia K562, human T-lymphoid CEM and murine leukemia L1210 cells markedly accumulated in the S phase of the cell cycle. In contrast to DNA replication, RNA synthesis (transcription) and protein synthesis (mRNA translation) were not affected by 9-(2-phosphonylmethoxyethyl)-adenine. The ribonucleoside triphosphate pools were slightly elevated, while the intracellular levels of all four deoxyribonucleoside triphosphates were 1.5-4-fold increased in 9-(2-phosphonylmethoxyethyl)adenine-treated K562, CEM and L1210 cells. The effect of 9-(2-phosphonylmethoxyethyl)adenine on de novo (thymidylate synthase-mediated) and salvage (thymidine kinase-mediated) dTTP synthesis was investigated using radio-labelled nucleoside precursors. The amount of thymidylate synthase-derived dTTP in the acid soluble pool was 2-4-fold higher in PMEA-treated than in untreated K562 cells, which is in accord with the 3-4-fold expansion of the global dTTP level in the presence of 9-(2-phosphonylmethoxyethyl)adenine. Strikingly, 2-derived dTTP accumulated to a much higher extent (i.e. 16-40-fold) in the soluble dTTP pool upon 9-(2-phosphonylmethoxyethyl)adenine treatment. In keeping with this finding, a markedly increased thymidine kinase activity could be demonstrated in extracts of 9-(2-phosphonylmethoxyethyl)adenine-treated K562 cell cultures. Also, in the presence of 200 microM 9-(2-phosphonylmethoxyethyl)adenine, 14-fold less thymidylate synthase-derived but only 3-fold less thymidine kinase-derived dTTP was incorporated into the DNA of the K562 cells. These data show that thymidine incorporation may be inappropriate as a cell proliferation marker in the presence of DNA synthesis inhibitors such as 9-(2-phosphonylmethoxyethyl)adenine. Our findings indicate that 9-(2-phosphonylmethoxyethyl)adenine causes a peculiar pattern of (deoxy)ribonucleotide metabolism deregulation in drug-treated tumor cells, as a result of the metabolic block imposed by the drug on the S phase of the cell cycle.  (+info)

A phase I study of the lipophilic thymidylate synthase inhibitor Thymitaq (nolatrexed dihydrochloride) given by 10-day oral administration. (6/1176)

2-Amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)-quinazoline dihydrochloride (nolatrexed dihydrochloride, Thymitaq, AG337), a specific inhibitor of thymidylate synthase, was developed using protein structure-based drug design. Intravenously administered nolatrexed is active clinically. As oral bioavailability is high (70-100%), nolatrexed was administered orally, 6 hourly for 10 days, at 3-week intervals, and dose escalated from 80 to 572 mg m(-2) day(-1) in 23 patients. Common toxicity criteria (CTC) grade 3 toxicities included nausea, vomiting, stomatitis and liver function test (LFT) abnormalities. Thrombocytopenia (grade 1 or 2) occurred at doses > or = 318 mg m(-2) day(-1) and neutropenia (grade 2) at 429 and 572 mg m(-2) day(-1). An erythematous maculopapular rash occurred at dosages > or = 318 mg m(-2) day(-1) (7 out of 19 patients). LFT abnormalities occurred in two out of six patients (grade 3 or 4 bilirubin and grade 3 alanine transaminase) at 572 mg m(-2) day(-1). Nolatrexed plasma concentrations 1 h after dosing were 6-16 microg ml(-1), and trough 3-8 microg ml(-1), at 572 mg m(-2) day(-1). Inhibition of thymidylate synthase was demonstrated by elevation of plasma deoxyuridine. Six-hourly oral nolatrexed for 10 days was associated with antiproliferative effects, but nausea and vomiting was dose limiting at 572 mg m(-2) day(-1). Nine patients were treated at 429 mg m(-2) day(-1); three out of nine experienced grade 3 nausea, but 17 out of 22 treatment courses were completed (with the co-administration of prophylactic antiemetics) and this dose level could be considered for phase II testing.  (+info)

Functional assessment of surface loops: deletion of eukaryote-specific peptide inserts in thymidylate synthase of Saccharomyces cerevisiae. (7/1176)

The primary structure is known for at least 29 thymidylate synthases and the crystal structure is known for several from both prokaryotes and eukaryotes. All these are markedly similar making thymidylate synthase one of the most highly conserved enzymes known. There are, however, two surface loops, one near the active site and the other near the dimer interface, which exist in distinctly prokaryotic and eukaryotic versions. Specifically, in eukaryotes these two surface loops have small peptide inserts conserved in size and partly conserved in sequence, that are not present in the prokaryotic thymidylate synthases. To address the possibility that these inserts provide eukaryote-specific functions the Saccharomyces cerevisiae loops were individually modified to mimic their prokaryotic counterparts. Altering the surface loop near the active site increased Km for the nucleotide substrate and decreased apparent Vmax. Mutant variants with alterations in the other surface loop were unable to dimerize. Therefore these surface loops have acquired, perhaps by way of the eukaryotic inserts, characteristics that are important for catalytic activity and quaternary structure respectively.  (+info)

Quercetin inhibited DNA synthesis and induced apoptosis associated with increase in c-fos mRNA level and the upregulation of p21WAF1CIP1 mRNA and protein expression during liver regeneration after partial hepatectomy. (8/1176)

Quercetin, a widely distributed bioflavonoid, inhibited DNA synthesis in regenerating liver after partial hepatectomy. This inhibition was accompanied by apoptosis, evidenced by in situ end-labeling and gel electrophoresis of DNA fragmentation. Characteristic DNA fragmentation was detected as early as 2 h after injection. Northern blot analysis revealed that quercetin induced the increases in c-fos and p21WAF1CIP1 mRNA levels within 2 h. The expression of p21 protein was also enhanced, while p53 mRNA and protein levels were not affected by quercetin. These results suggest that quercetin-induced apoptosis is associated with the increase in c-fos mRNA level and the upregulation of p21 mRNA and protein expression, probably in a p53-independent pathway.  (+info)

Thymidylate synthase (TS) is an essential enzyme in the metabolic pathway for DNA synthesis and repair. It catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), which is a crucial building block for DNA replication and repair. This reaction also involves the methylation of dUMP using a methyl group donated by N5,N10-methylenetetrahydrofolate, resulting in the formation of dihydrofolate as a byproduct. The regeneration of dihydrofolate to tetrahydrofolate is necessary for TS to continue functioning, making it dependent on the folate cycle. Thymidylate synthase inhibitors are used in cancer chemotherapy to interfere with DNA synthesis and replication, leading to cytotoxic effects in rapidly dividing cells.

Fluorodeoxyuridylate (FdU) is not a medical term itself, but it is a chemical compound that plays a role in the mechanism of action of certain chemotherapeutic drugs. FdU is a thymidine analogue, which means it is a synthetic molecule similar to one of the building blocks of DNA called thymidine.

FdU can be incorporated into DNA during replication, leading to the inhibition of DNA synthesis and ultimately cell death. This mechanism of action is shared by several chemotherapeutic drugs, such as fluorouracil (5-FU) and capecitabine, which are converted into FdU in the body.

Therefore, while Fluorodeoxyuridylate itself is not a medical term, it is an important concept in understanding how certain chemotherapeutic drugs work to inhibit cancer cell growth and division.

Deoxyuracil nucleotides are chemical compounds that are the building blocks of DNA. Specifically, they are the form of nucleotides that contain the sugar deoxyribose and the nucleobase deoxyuracil. In DNA, deoxyuracil nucleotides pair with deoxyadenosine nucleotides through base pairing.

Deoxyuracil is a nucleobase that is similar to thymine, but it lacks a methyl group. Thymine is the usual nucleobase that pairs with adenine in DNA, while uracil is typically found in RNA paired with adenine. However, in certain circumstances, such as during DNA repair or damage, deoxyuracil can be incorporated into DNA instead of thymine.

Deoxyuracil nucleotides are important for understanding DNA replication, repair, and mutation. Abnormalities in the incorporation or removal of deoxyuracil nucleotides can lead to genetic disorders, cancer, and other diseases.

Thymidine Monophosphate (TMP or dTMP) is a nucleotide that is a ester of phosphoric acid with thymidine, a nucleoside consisting of deoxyribose sugar linked to the nitrogenous base thymine. It is one of the four monophosphate nucleotides that are the building blocks of DNA, along with adenosine monophosphate (AMP), guanosine monophosphate (GMP), and cytidine monophosphate (CMP). TMP plays a crucial role in DNA replication and repair processes. It is also used as a marker in biochemical research and medical diagnostics.

Folic acid antagonists are a class of medications that work by inhibiting the action of folic acid or its metabolic pathways. These drugs are commonly used in the treatment of various types of cancer and certain other conditions, such as rheumatoid arthritis. They include drugs such as methotrexate, pemetrexed, and trimetrexate.

Folic acid is a type of B vitamin that is essential for the production of DNA and RNA, the genetic material found in cells. Folic acid antagonists work by interfering with the enzyme responsible for converting folic acid into its active form, tetrahydrofolate. This interference prevents the formation of new DNA and RNA, which is necessary for cell division and growth. As a result, these drugs can inhibit the proliferation of rapidly dividing cells, such as cancer cells.

It's important to note that folic acid antagonists can also affect normal, non-cancerous cells in the body, particularly those that divide quickly, such as cells in the bone marrow and digestive tract. This can lead to side effects such as anemia, mouth sores, and diarrhea. Therefore, these drugs must be used carefully and under the close supervision of a healthcare provider.

Floxuridine is a chemotherapeutic antimetabolite medication that is primarily used in the treatment of colon cancer. It is a fluorinated pyrimidine nucleoside analogue, which means it is similar in structure to the building blocks of DNA and RNA, and can be incorporated into these molecules during cell division, disrupting their normal function and preventing cell replication.

Floxuridine works by inhibiting the enzyme thymidylate synthase, which is necessary for the synthesis of thymidine, a nucleoside that is essential for DNA replication. By blocking this enzyme, floxuridine can prevent the growth and proliferation of cancer cells.

Floxuridine is often used in combination with other chemotherapy drugs as part of a treatment regimen for colon cancer. It may be administered intravenously or via continuous infusion, depending on the specific treatment plan. As with all chemotherapy drugs, floxuridine can have significant side effects, including nausea, vomiting, diarrhea, and myelosuppression (suppression of bone marrow function), which can lead to anemia, neutropenia, and thrombocytopenia.

Antimetabolites are a class of antineoplastic (chemotherapy) drugs that interfere with the metabolism of cancer cells and inhibit their growth and proliferation. These agents are structurally similar to naturally occurring metabolites, such as amino acids, nucleotides, and folic acid, which are essential for cellular replication and growth. Antimetabolites act as false analogs and get incorporated into the growing cells' DNA or RNA, causing disruption of the normal synthesis process, leading to cell cycle arrest and apoptosis (programmed cell death).

Examples of antimetabolite drugs include:

1. Folate antagonists: Methotrexate, Pemetrexed
2. Purine analogs: Mercaptopurine, Thioguanine, Fludarabine, Cladribine
3. Pyrimidine analogs: 5-Fluorouracil (5-FU), Capecitabine, Cytarabine, Gemcitabine

These drugs are used to treat various types of cancers, such as leukemias, lymphomas, breast, ovarian, and gastrointestinal cancers. Due to their mechanism of action, antimetabolites can also affect normal, rapidly dividing cells in the body, leading to side effects like myelosuppression (decreased production of blood cells), mucositis (inflammation and ulceration of the gastrointestinal tract), and alopecia (hair loss).

Thiophenes are organic compounds that contain a heterocyclic ring made up of four carbon atoms and one sulfur atom. The structure of thiophene is similar to benzene, with the benzene ring being replaced by a thiophene ring. Thiophenes are aromatic compounds, which means they have a stable, planar ring structure and delocalized electrons.

Thiophenes can be found in various natural sources such as coal tar, crude oil, and some foods like onions and garlic. They also occur in certain medications, dyes, and pesticides. Some thiophene derivatives have been synthesized and studied for their potential therapeutic uses, including anti-inflammatory, antiviral, and antitumor activities.

In the medical field, thiophenes are used in some pharmaceuticals as building blocks to create drugs with various therapeutic effects. For example, tipepidine, a cough suppressant, contains a thiophene ring. Additionally, some anesthetics and antipsychotic medications also contain thiophene moieties.

It is important to note that while thiophenes themselves are not typically considered medical terms, they play a role in the chemistry of various pharmaceuticals and other medical-related compounds.

Tetrahydrofolates (THFs) are a type of folate, which is a form of vitamin B9. Folate is essential for the production and maintenance of new cells, especially in DNA synthesis and methylation. THFs are the active forms of folate in the body and are involved in various metabolic processes, including:

1. The conversion of homocysteine to methionine, an amino acid required for protein synthesis and the formation of S-adenosylmethionine (SAM), a major methyl donor in the body.
2. The transfer of one-carbon units in various metabolic reactions, such as the synthesis of purines and pyrimidines, which are essential components of DNA and RNA.
3. The remethylation of homocysteine to methionine, a process that helps maintain normal homocysteine levels in the body. Elevated homocysteine levels have been linked to an increased risk of cardiovascular disease.

THFs can be obtained from dietary sources, such as leafy green vegetables, legumes, and fortified cereals. They can also be synthesized endogenously in the body through the action of the enzyme dihydrofolate reductase (DHFR), which reduces dihydrofolate (DHF) to THF using NADPH as a cofactor.

Deficiencies in folate or impaired THF metabolism can lead to various health issues, including megaloblastic anemia, neural tube defects during fetal development, and an increased risk of cardiovascular disease due to elevated homocysteine levels.

Fluorouracil is a antineoplastic medication, which means it is used to treat cancer. It is a type of chemotherapy drug known as an antimetabolite. Fluorouracil works by interfering with the growth of cancer cells and ultimately killing them. It is often used to treat colon, esophageal, stomach, and breast cancers, as well as skin conditions such as actinic keratosis and superficial basal cell carcinoma. Fluorouracil may be given by injection or applied directly to the skin in the form of a cream.

It is important to note that fluorouracil can have serious side effects, including suppression of bone marrow function, mouth sores, stomach and intestinal ulcers, and nerve damage. It should only be used under the close supervision of a healthcare professional.

Quinazolines are not a medical term per se, but they are a class of organic compounds that have been widely used in the development of various pharmaceutical drugs. Therefore, I will provide you with a chemical definition of quinazolines:

Quinazolines are heterocyclic aromatic organic compounds consisting of a benzene ring fused to a pyrazine ring. The structure can be represented as follows:

Quinazoline

They are often used as building blocks in the synthesis of various drugs, including those used for treating cancer, cardiovascular diseases, and microbial infections. Some examples of FDA-approved drugs containing a quinazoline core include the tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva), which are used to treat non-small cell lung cancer, and the calcium channel blocker verapamil (Calan, Isoptin), which is used to treat hypertension and angina.

Nucleoside-phosphate kinase (NPK) is an enzyme that plays a crucial role in the synthesis and metabolism of nucleotides, which are the building blocks of DNA and RNA. NPK catalyzes the transfer of a phosphate group from a donor molecule, typically ATP, to a nucleoside or deoxynucleoside, forming a nucleoside monophosphate (NMP) or deoxynucleoside monophosphate (dNMP).

There are several isoforms of NPK found in different cellular compartments and tissues, each with distinct substrate specificities. These enzymes play essential roles in maintaining the balance of nucleotides required for various cellular processes, including DNA replication, repair, and transcription, as well as RNA synthesis and metabolism.

Abnormalities in NPK activity or expression have been implicated in several human diseases, such as cancer, viral infections, and neurological disorders. Therefore, understanding the function and regulation of NPK is crucial for developing novel therapeutic strategies to target these conditions.

Isoindoles are not typically considered in the context of medical definitions, as they are organic compounds that do not have direct relevance to medical terminology or human disease. However, isoindole is a heterocyclic compound that contains two nitrogen atoms in its structure and can be found in some naturally occurring substances and synthetic drugs.

Isoindoles are aromatic compounds, which means they have a stable ring structure with delocalized electrons. They can form the core structure of various bioactive molecules, including alkaloids, which are nitrogen-containing compounds that occur naturally in plants and animals and can have various pharmacological activities.

Some isoindole derivatives have been synthesized and studied for their potential medicinal properties, such as anti-inflammatory, antiviral, and anticancer activities. However, these compounds are still in the early stages of research and development and have not yet been approved for medical use.

Therefore, while isoindoles themselves do not have a specific medical definition, they can be relevant to the study of medicinal chemistry and drug discovery.

Trimetrexate is a antifolate drug, which means it interferes with the use of folic acid in the body. It is primarily used in the treatment of certain types of cancer and parasitic infections. Trimetrexate works by blocking the action of an enzyme called dihydrofolate reductase, which is necessary for the production of DNA and RNA, the genetic material found in cells. By inhibiting this enzyme, trimetrexate can help to stop the growth and multiplication of cancer cells or parasites.

In medical terms, Trimetrexate is classified as an antineoplastic agent and an antiprotozoal agent. It may be used to treat certain types of cancer such as non-Hodgkin's lymphoma, and it may also be used to treat parasitic infections caused by Pneumocystis jirovecii (formerly known as Pneumocystis carinii) in patients with weakened immune systems.

It is important to note that Trimetrexate can have significant side effects and should only be used under the close supervision of a healthcare provider.

Deoxyuridine is a chemical compound that is a component of DNA. It is a nucleoside, which means it consists of a sugar (deoxyribose) linked to a nitrogenous base (uracil). In the case of deoxyuridine, the uracil is not methylated, which differentiates it from thymidine.

Deoxyuridine can be converted into deoxyuridine monophosphate (dUMP) by the enzyme thymidine kinase. The dUMP can then be converted into deoxythymidine triphosphate (dTTP), which is a building block of DNA, through a series of reactions involving other enzymes.

Deoxyuridine has been used in research and medicine as a marker for DNA synthesis and repair. It can also be used to inhibit the growth of certain types of cells, such as cancer cells, by disrupting their DNA synthesis.

Folic acid is the synthetic form of folate, a type of B vitamin (B9). It is widely used in dietary supplements and fortified foods because it is more stable and has a longer shelf life than folate. Folate is essential for normal cell growth and metabolism, and it plays a critical role in the formation of DNA and RNA, the body's genetic material. Folic acid is also crucial during early pregnancy to prevent birth defects of the brain and spine called neural tube defects.

Medical Definition: "Folic acid is the synthetic form of folate (vitamin B9), a water-soluble vitamin involved in DNA synthesis, repair, and methylation. It is used in dietary supplementation and food fortification due to its stability and longer shelf life compared to folate. Folic acid is critical for normal cell growth, development, and red blood cell production."

Lactobacillus casei is a species of Gram-positive, rod-shaped bacteria that belongs to the genus Lactobacillus. These bacteria are commonly found in various environments, including the human gastrointestinal tract, and are often used in food production, such as in the fermentation of dairy products like cheese and yogurt.

Lactobacillus casei is known for its ability to produce lactic acid, which gives it the name "lactic acid bacterium." This characteristic makes it an important player in maintaining a healthy gut microbiome, as it helps to lower the pH of the gut and inhibit the growth of harmful bacteria.

In addition to its role in food production and gut health, Lactobacillus casei has been studied for its potential probiotic benefits. Probiotics are live bacteria and yeasts that are beneficial to human health, particularly the digestive system. Some research suggests that Lactobacillus casei may help support the immune system, improve digestion, and alleviate symptoms of certain gastrointestinal disorders like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). However, more research is needed to fully understand its potential health benefits and applications.

Tetrahydrofolate dehydrogenase (EC 1.5.1.20) is an enzyme involved in folate metabolism. The enzyme catalyzes the oxidation of tetrahydrofolate (THF) to dihydrofolate (DHF), while simultaneously reducing NADP+ to NADPH.

The reaction can be summarized as follows:

THF + NADP+ -> DHF + NADPH + H+

This enzyme plays a crucial role in the synthesis of purines and thymidylate, which are essential components of DNA and RNA. Therefore, any defects or deficiencies in tetrahydrofolate dehydrogenase can lead to various medical conditions, including megaloblastic anemia and neural tube defects during fetal development.

Pteroylpolyglutamic acids are forms of folic acid that are composed of multiple glutamic acid molecules linked together in a chain. This compound is also known as polyglutamated folate or folylpolyglutamates. The length of the glutamic acid chain can vary, and these compounds are often found naturally in foods such as leafy green vegetables, fruits, and dried beans.

In the body, pteroylpolyglutamic acids must be converted to the active form of folate, called tetrahydrofolate, before they can participate in various metabolic processes, including DNA synthesis and methylation reactions. Some people may have difficulty absorbing or converting these compounds due to genetic factors or certain medical conditions, which can lead to folate deficiency and related health problems.

It's worth noting that supplemental forms of folic acid are typically in the form of a single glutamate molecule (pteroylmonoglutamic acid) and may not be as effective at raising folate levels in the body as the polyglutamated forms found in food. However, the monoglutamate form is more easily absorbed and utilized by the body, making it a common choice for supplementation.

Leukemia L1210 is not a medical definition itself, but it refers to a specific mouse leukemia cell line that was established in 1948. These cells are a type of acute myeloid leukemia (AML) and have been widely used in cancer research as a model for studying the disease, testing new therapies, and understanding the biology of leukemia. The L1210 cell line has contributed significantly to the development of various chemotherapeutic agents and treatment strategies for leukemia and other cancers.

Polyglutamic acid (PGA) is not a medical term per se, but it is a term used in biochemistry and cosmetics. Medically, it may be mentioned in the context of certain medical conditions or treatments. Here's a definition:

Polyglutamic acid is a polymer of glutamic acid, a type of amino acid. It is a natural substance found in various foods such as natto, a traditional Japanese fermented soybean dish. In the human body, it is produced by certain bacteria during fermentation processes.

PGA has been studied for its potential medical applications due to its unique properties, including its ability to retain moisture and form gels. It has been explored as a wound dressing material, drug delivery vehicle, and anti-aging cosmetic ingredient. However, it is not a widely used or recognized medical treatment at this time.

Methyltransferases are a class of enzymes that catalyze the transfer of a methyl group (-CH3) from a donor molecule to an acceptor molecule, which is often a protein, DNA, or RNA. This transfer of a methyl group can modify the chemical and physical properties of the acceptor molecule, playing a crucial role in various cellular processes such as gene expression, signal transduction, and DNA repair.

In biochemistry, methyltransferases are classified based on the type of donor molecule they use for the transfer of the methyl group. The most common methyl donor is S-adenosylmethionine (SAM), a universal methyl group donor found in many organisms. Methyltransferases that utilize SAM as a cofactor are called SAM-dependent methyltransferases.

Abnormal regulation or function of methyltransferases has been implicated in several diseases, including cancer and neurological disorders. Therefore, understanding the structure, function, and regulation of these enzymes is essential for developing targeted therapies to treat these conditions.

Thymidine phosphorylase (TP) is an enzyme that plays a role in the metabolism of nucleosides, specifically thymidine. The medical definition of thymidine phosphorylase is:

An enzyme that catalyzes the conversion of thymidine to thymine and deoxyribose-1-phosphate. Thymidine phosphorylase has been identified as a key enzyme in the angiogenic (formation of new blood vessels) pathway, where it facilitates the release of pro-angiogenic factors such as vascular endothelial growth factor (VEGF).

In addition to its role in nucleoside metabolism and angiogenesis, thymidine phosphorylase has been implicated in cancer biology. Increased levels of thymidine phosphorylase have been found in various human cancers, including colorectal, breast, lung, and pancreatic cancers. These high levels of thymidine phosphorylase are associated with poor prognosis and increased angiogenesis, contributing to tumor growth and metastasis.

Thus, thymidine phosphorylase is a crucial enzyme in nucleoside metabolism, angiogenesis, and cancer biology, making it an important target for the development of novel anti-cancer therapies.

Methotrexate is a medication used in the treatment of certain types of cancer and autoimmune diseases. It is an antimetabolite that inhibits the enzyme dihydrofolate reductase, which is necessary for the synthesis of purines and pyrimidines, essential components of DNA and RNA. By blocking this enzyme, methotrexate interferes with cell division and growth, making it effective in treating rapidly dividing cells such as cancer cells.

In addition to its use in cancer treatment, methotrexate is also used to manage autoimmune diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. In these conditions, methotrexate modulates the immune system and reduces inflammation.

It's important to note that methotrexate can have significant side effects and should be used under the close supervision of a healthcare provider. Regular monitoring of blood counts, liver function, and kidney function is necessary during treatment with methotrexate.

Thymine nucleotides are biochemical components that play a crucial role in the structure and function of DNA (deoxyribonucleic acid), which is the genetic material present in living organisms. A thymine nucleotide consists of three parts: a sugar molecule called deoxyribose, a phosphate group, and a nitrogenous base called thymine.

Thymine is one of the four nucleobases in DNA, along with adenine, guanine, and cytosine. It specifically pairs with adenine through hydrogen bonding, forming a base pair that is essential for maintaining the structure and stability of the double helix. Thymine nucleotides are linked together by phosphodiester bonds between the sugar molecules of adjacent nucleotides, creating a long, linear polymer known as a DNA strand.

In summary, thymine nucleotides are building blocks of DNA that consist of deoxyribose, a phosphate group, and the nitrogenous base thymine, which pairs with adenine in the double helix structure.

Thymidine is a pyrimidine nucleoside that consists of a thymine base linked to a deoxyribose sugar by a β-N1-glycosidic bond. It plays a crucial role in DNA replication and repair processes as one of the four nucleosides in DNA, along with adenosine, guanosine, and cytidine. Thymidine is also used in research and clinical settings for various purposes, such as studying DNA synthesis or as a component of antiviral and anticancer therapies.

Leucovorin is the pharmaceutical name for a form of folic acid, also known as folinic acid. It is used in medicine as a medication to reduce the toxic effects of certain chemotherapy drugs, such as methotrexate, that work by blocking the action of folic acid in the body. Leucovorin is able to bypass this blockage and restore some of the necessary functions of folic acid, helping to prevent or reduce the severity of side effects like nausea, vomiting, and damage to the mucous membranes.

Leucovorin may also be used in combination with fluorouracil chemotherapy to enhance its effectiveness in treating certain types of cancer. It is important to note that leucovorin should only be used under the supervision of a healthcare professional, as it can interact with other medications and have potentially serious side effects if not used properly.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

Glycine hydroxymethyltransferase (GHMT or GHT) is an enzyme that plays a crucial role in the metabolic pathway called the methylation cycle, specifically in the synthesis of the amino acid serine and the conversion of glycine. It catalyzes the reversible reaction between glycine and methylene tetrahydrofolate (MTHF) to produce 5,10-methylenetetrahydrofolate and sarcosine.

The reaction can be represented as follows:
Glycine + MTHF ↔ Sarcosine + 5,10-methylenetetrahydrofolate

This enzyme is widely distributed in various tissues, including the liver, kidney, and pancreas. In addition to its role in amino acid metabolism, GHMT also contributes to the regulation of one-carbon metabolism, which is essential for methylation reactions, DNA synthesis, and cellular homeostasis.

Hydroxymethyl and Formyl Transferases are a class of enzymes that catalyze the transfer of hydroxymethyl or formyl groups from one molecule to another. These enzymes play important roles in various metabolic pathways, including the synthesis and modification of nucleotides, amino acids, and other biomolecules.

One example of a Hydroxymethyl Transferase is DNA methyltransferase (DNMT), which catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to the 5-carbon of cytosine residues in DNA, forming 5-methylcytosine. This enzyme can also function as a Hydroxymethyl Transferase by catalyzing the transfer of a hydroxymethyl group from SAM to cytosine residues, forming 5-hydroxymethylcytosine.

Formyl Transferases are another class of enzymes that catalyze the transfer of formyl groups from one molecule to another. One example is formyltransferase domain containing protein 1 (FTCD1), which catalyzes the transfer of a formyl group from 10-formyltetrahydrofolate to methionine, forming N5-formiminotetrahydrofolate and methionine semialdehyde.

These enzymes are essential for maintaining proper cellular function and are involved in various physiological processes, including gene regulation, DNA repair, and metabolism. Dysregulation of these enzymes has been implicated in several diseases, including cancer, neurological disorders, and cardiovascular disease.

Orotate phosphoribosyltransferase (OPRT) is an enzyme that catalyzes the conversion of orotate to oximine monophosphate (OMP), which is a key step in the biosynthesis of pyrimidines, a type of nucleotide. This enzyme plays a crucial role in the metabolism of nucleic acids, which are the building blocks of DNA and RNA.

The reaction catalyzed by OPRT is as follows:

orotate + phosphoribosyl pyrophosphate (PRPP) -> oximine monophosphate (OMP) + pyrophosphate

Defects in the gene that encodes for OPRT can lead to orotic aciduria, a rare genetic disorder characterized by an accumulation of orotic acid and other pyrimidines in the urine and other body fluids. Symptoms of this condition may include developmental delay, mental retardation, seizures, and megaloblastic anemia.

Colonic neoplasms refer to abnormal growths in the large intestine, also known as the colon. These growths can be benign (non-cancerous) or malignant (cancerous). The two most common types of colonic neoplasms are adenomas and carcinomas.

Adenomas are benign tumors that can develop into cancer over time if left untreated. They are often found during routine colonoscopies and can be removed during the procedure.

Carcinomas, on the other hand, are malignant tumors that invade surrounding tissues and can spread to other parts of the body. Colorectal cancer is the third leading cause of cancer-related deaths in the United States, and colonic neoplasms are a significant risk factor for developing this type of cancer.

Regular screenings for colonic neoplasms are recommended for individuals over the age of 50 or those with a family history of colorectal cancer or other risk factors. Early detection and removal of colonic neoplasms can significantly reduce the risk of developing colorectal cancer.

Colorectal neoplasms refer to abnormal growths in the colon or rectum, which can be benign or malignant. These growths can arise from the inner lining (mucosa) of the colon or rectum and can take various forms such as polyps, adenomas, or carcinomas.

Benign neoplasms, such as hyperplastic polyps and inflammatory polyps, are not cancerous but may need to be removed to prevent the development of malignant tumors. Adenomas, on the other hand, are precancerous lesions that can develop into colorectal cancer if left untreated.

Colorectal cancer is a malignant neoplasm that arises from the uncontrolled growth and division of cells in the colon or rectum. It is one of the most common types of cancer worldwide and can spread to other parts of the body through the bloodstream or lymphatic system.

Regular screening for colorectal neoplasms is recommended for individuals over the age of 50, as early detection and removal of precancerous lesions can significantly reduce the risk of developing colorectal cancer.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Glutamates are the salt or ester forms of glutamic acid, which is a naturally occurring amino acid and the most abundant excitatory neurotransmitter in the central nervous system. Glutamate plays a crucial role in various brain functions, such as learning, memory, and cognition. However, excessive levels of glutamate can lead to neuronal damage or death, contributing to several neurological disorders, including stroke, epilepsy, and neurodegenerative diseases like Alzheimer's and Parkinson's.

Glutamates are also commonly found in food as a natural flavor enhancer, often listed under the name monosodium glutamate (MSG). While MSG has been extensively studied, its safety remains a topic of debate, with some individuals reporting adverse reactions after consuming foods containing this additive.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

The Reduced Folate Carrier Protein (RFC) is also known as the Folate Receptor Alpha (FR-α). It is a transmembrane protein responsible for the cellular influx of reduced folates, which are essential cofactors in various metabolic processes, particularly DNA synthesis and methylation. These processes are vital for cell growth, division, and development.

Reduced Folate Carrier Protein is widely expressed in many tissues, including the kidneys, liver, intestines, and choroid plexus. It plays a crucial role in maintaining intracellular folate homeostasis by facilitating the uptake of reduced folates from circulation into cells.

Dysfunctions or mutations in the RFC gene can lead to impaired folate transport, which may result in various clinical manifestations, such as megaloblastic anemia and neurological disorders. Proper folate status is essential for overall health, particularly during pregnancy and fetal development, as it helps prevent neural tube defects in newborns.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

'Escherichia coli' (E. coli) is a type of gram-negative, facultatively anaerobic, rod-shaped bacterium that commonly inhabits the intestinal tract of humans and warm-blooded animals. It is a member of the family Enterobacteriaceae and one of the most well-studied prokaryotic model organisms in molecular biology.

While most E. coli strains are harmless and even beneficial to their hosts, some serotypes can cause various forms of gastrointestinal and extraintestinal illnesses in humans and animals. These pathogenic strains possess virulence factors that enable them to colonize and damage host tissues, leading to diseases such as diarrhea, urinary tract infections, pneumonia, and sepsis.

E. coli is a versatile organism with remarkable genetic diversity, which allows it to adapt to various environmental niches. It can be found in water, soil, food, and various man-made environments, making it an essential indicator of fecal contamination and a common cause of foodborne illnesses. The study of E. coli has contributed significantly to our understanding of fundamental biological processes, including DNA replication, gene regulation, and protein synthesis.

'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.

The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.

It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.

Lentinan is a polysaccharide derived from the shiitake mushroom (Lentinula edodes) that has been studied for its potential immune-enhancing and anti-cancer effects. It is a beta-glucan with a complex structure, including both β-(1,3)-D-glucan and β-(1,6)-D-glucan branches.

In the medical context, lentinan is considered an immunomodulator, as it can stimulate various immune cells like macrophages, neutrophils, and natural killer (NK) cells. These immune cells play crucial roles in recognizing and eliminating foreign substances, including cancer cells and pathogens.

Lentinan has been investigated for its potential therapeutic benefits in treating several types of cancer, such as gastric, colorectal, and breast cancers. However, most of the research is still preclinical or based on small-scale clinical trials, so more extensive studies are needed to confirm its efficacy and safety before it can be widely adopted in medical practice.

It's important to note that lentinan supplements should not replace conventional cancer treatments but may potentially be used as an adjunct therapy under the guidance of a healthcare professional.

Thymidine kinase (TK) is an enzyme that plays a crucial role in the synthesis of thymidine triphosphate (dTMP), a nucleotide required for DNA replication and repair. It catalyzes the phosphorylation of thymidine to thymidine monophosphate (dTMP) by transferring a phosphate group from adenosine triphosphate (ATP).

There are two major isoforms of thymidine kinase in humans: TK1 and TK2. TK1 is primarily found in the cytoplasm of proliferating cells, such as those involved in the cell cycle, while TK2 is located mainly in the mitochondria and is responsible for maintaining the dNTP pool required for mtDNA replication and repair.

Thymidine kinase activity has been used as a marker for cell proliferation, particularly in cancer cells, which often exhibit elevated levels of TK1 due to their high turnover rates. Additionally, measuring TK1 levels can help monitor the effectiveness of certain anticancer therapies that target DNA replication.

Guanine is not a medical term per se, but it is a biological molecule that plays a crucial role in the body. Guanine is one of the four nucleobases found in the nucleic acids DNA and RNA, along with adenine, cytosine, and thymine (in DNA) or uracil (in RNA). Specifically, guanine pairs with cytosine via hydrogen bonds to form a base pair.

Guanine is a purine derivative, which means it has a double-ring structure. It is formed through the synthesis of simpler molecules in the body and is an essential component of genetic material. Guanine's chemical formula is C5H5N5O.

While guanine itself is not a medical term, abnormalities or mutations in genes that contain guanine nucleotides can lead to various medical conditions, including genetic disorders and cancer.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase is also known as Methionine Synthase. It is a vital enzyme in the human body that plays a crucial role in methionine metabolism and homocysteine regulation.

The medical definition of 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase is as follows:

A enzyme (EC 2.1.1.13) that catalyzes the methylation of homocysteine to methionine, using 5-methyltetrahydrofolate as a methyl donor. This reaction also requires the cofactor vitamin B12 (cobalamin) as a coenzyme. The enzyme is located in the cytosol of cells and is essential for the synthesis of methionine, which is an important amino acid required for various biological processes such as protein synthesis, methylation reactions, and the formation of neurotransmitters.

Deficiency or dysfunction of this enzyme can lead to several health issues, including homocystinuria, a genetic disorder characterized by elevated levels of homocysteine in the blood, which can cause serious complications such as neurological damage, cardiovascular disease, and skeletal abnormalities.

Phosphoribosylaminoimidazolecarboxamide formyltransferase (AIRFT) is an enzyme involved in the purine nucleotide biosynthesis pathway. The systematic medical name for this enzyme is "phosphoribosylaminoimidazole carboxamide formyltransferase, IMP cyclohydrolase, and GMP synthase."

The primary function of AIRFT is to catalyze the conversion of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to formylated AICAR (FAICAR), which is an essential step in the synthesis of inosine monophosphate (IMP). IMP is a key precursor for the biosynthesis of both adenine and guanine nucleotides.

The enzyme's activity can be measured by determining the rate of conversion of AICAR to FAICAR, which requires the presence of 10-formyltetrahydrofolate (10-Formyl-THF) as a cofactor. Deficiency in this enzyme can lead to impaired purine synthesis and may result in various clinical manifestations such as developmental delay, neurological symptoms, and immunodeficiency.

Glycogen synthase is an enzyme (EC 2.4.1.11) that plays a crucial role in the synthesis of glycogen, a polysaccharide that serves as the primary storage form of glucose in animals, fungi, and bacteria. This enzyme catalyzes the transfer of glucosyl residues from uridine diphosphate glucose (UDP-glucose) to the non-reducing end of an growing glycogen chain, thereby elongating it.

Glycogen synthase is regulated by several mechanisms, including allosteric regulation and covalent modification. The activity of this enzyme is inhibited by high levels of intracellular glucose-6-phosphate (G6P) and activated by the binding of glycogen or proteins that bind to glycogen, such as glycogenin. Phosphorylation of glycogen synthase by protein kinases, like glycogen synthase kinase-3 (GSK3), also reduces its activity, while dephosphorylation by protein phosphatases enhances it.

The regulation of glycogen synthase is critical for maintaining glucose homeostasis and energy balance in the body. Dysregulation of this enzyme has been implicated in several metabolic disorders, including type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).

Phosphoribosylglycinamide formyltransferase (PGTF) is an enzyme involved in the biosynthesis of purine nucleotides, which are essential components of DNA and RNA. The systematic medical definition of PGTF is:

"An enzyme that catalyzes the transfer of a formyl group from 10-formyltetrahydrofolate to the amino group of phosphoribosylglycinamide, forming N-formylphosphoribosylglycinamide and tetrahydrofolate as byproducts. This reaction is the fourth step in the de novo synthesis pathway of purine nucleotides."

PGTF's gene name is GART (Glycinamide Ribonucleotide Transformylase), and it is located on human chromosome 10q24.32-q25.1. Mutations in the GART gene can lead to a rare autosomal recessive disorder called Lesch-Nyhan syndrome, which is characterized by hyperuricemia, neurological symptoms, and self-mutilating behavior.

Glycogen Synthase Kinase 3 (GSK-3) is a serine/threonine protein kinase that plays a crucial role in the regulation of several cellular processes, including glycogen metabolism, cell signaling, gene transcription, and apoptosis. It was initially discovered as a key enzyme involved in glycogen metabolism due to its ability to phosphorylate and inhibit glycogen synthase, an enzyme responsible for the synthesis of glycogen from glucose.

GSK-3 exists in two isoforms, GSK-3α and GSK-3β, which share a high degree of sequence similarity and are widely expressed in various tissues. Both isoforms are constitutively active under normal conditions and are regulated through inhibitory phosphorylation by several upstream signaling pathways, such as insulin, Wnt, and Hedgehog signaling.

Dysregulation of GSK-3 has been implicated in the pathogenesis of various diseases, including diabetes, neurodegenerative disorders, and cancer. In recent years, GSK-3 has emerged as an attractive therapeutic target for the development of novel drugs to treat these conditions.

Drug resistance in neoplasms (also known as cancer drug resistance) refers to the ability of cancer cells to withstand the effects of chemotherapeutic agents or medications designed to kill or inhibit the growth of cancer cells. This can occur due to various mechanisms, including changes in the cancer cell's genetic makeup, alterations in drug targets, increased activity of drug efflux pumps, and activation of survival pathways.

Drug resistance can be intrinsic (present at the beginning of treatment) or acquired (developed during the course of treatment). It is a significant challenge in cancer therapy as it often leads to reduced treatment effectiveness, disease progression, and poor patient outcomes. Strategies to overcome drug resistance include the use of combination therapies, development of new drugs that target different mechanisms, and personalized medicine approaches that consider individual patient and tumor characteristics.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Nitric Oxide Synthase Type I, also known as NOS1 or neuronal nitric oxide synthase (nNOS), is an enzyme that catalyzes the production of nitric oxide (NO) from L-arginine. It is primarily expressed in the nervous system, particularly in neurons, and plays a crucial role in the regulation of neurotransmission, synaptic plasticity, and cerebral blood flow. NOS1 is calcium-dependent and requires several cofactors for its activity, including NADPH, FAD, FMN, and calmodulin. It is involved in various physiological and pathological processes, such as learning and memory, seizure susceptibility, and neurodegenerative disorders.

Uracil is not a medical term, but it is a biological molecule. Medically or biologically, uracil can be defined as one of the four nucleobases in the nucleic acid of RNA (ribonucleic acid) that is linked to a ribose sugar by an N-glycosidic bond. It forms base pairs with adenine in double-stranded RNA and DNA. Uracil is a pyrimidine derivative, similar to thymine found in DNA, but it lacks the methyl group (-CH3) that thymine has at the 5 position of its ring.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Genetic polymorphism refers to the occurrence of multiple forms (called alleles) of a particular gene within a population. These variations in the DNA sequence do not generally affect the function or survival of the organism, but they can contribute to differences in traits among individuals. Genetic polymorphisms can be caused by single nucleotide changes (SNPs), insertions or deletions of DNA segments, or other types of genetic rearrangements. They are important for understanding genetic diversity and evolution, as well as for identifying genetic factors that may contribute to disease susceptibility in humans.

Drug resistance, also known as antimicrobial resistance, is the ability of a microorganism (such as bacteria, viruses, fungi, or parasites) to withstand the effects of a drug that was originally designed to inhibit or kill it. This occurs when the microorganism undergoes genetic changes that allow it to survive in the presence of the drug. As a result, the drug becomes less effective or even completely ineffective at treating infections caused by these resistant organisms.

Drug resistance can develop through various mechanisms, including mutations in the genes responsible for producing the target protein of the drug, alteration of the drug's target site, modification or destruction of the drug by enzymes produced by the microorganism, and active efflux of the drug from the cell.

The emergence and spread of drug-resistant microorganisms pose significant challenges in medical treatment, as they can lead to increased morbidity, mortality, and healthcare costs. The overuse and misuse of antimicrobial agents, as well as poor infection control practices, contribute to the development and dissemination of drug-resistant strains. To address this issue, it is crucial to promote prudent use of antimicrobials, enhance surveillance and monitoring of resistance patterns, invest in research and development of new antimicrobial agents, and strengthen infection prevention and control measures.

Tandem Repeat Sequences (TRS) in genetics refer to repeating DNA sequences that are arranged directly after each other, hence the term "tandem." These sequences consist of a core repeat unit that is typically 2-6 base pairs long and is repeated multiple times in a head-to-tail fashion. The number of repetitions can vary between individuals and even between different cells within an individual, leading to genetic heterogeneity.

TRS can be classified into several types based on the number of repeat units and their stability. Short Tandem Repeats (STRs), also known as microsatellites, have fewer than 10 repeats, while Minisatellites have 10-60 repeats. Variations in the number of these repeats can lead to genetic instability and are associated with various genetic disorders and diseases, including neurological disorders, cancer, and forensic identification.

It's worth noting that TRS can also occur in protein-coding regions of genes, leading to the production of repetitive amino acid sequences. These can affect protein structure and function, contributing to disease phenotypes.

Molecular cloning is a laboratory technique used to create multiple copies of a specific DNA sequence. This process involves several steps:

1. Isolation: The first step in molecular cloning is to isolate the DNA sequence of interest from the rest of the genomic DNA. This can be done using various methods such as PCR (polymerase chain reaction), restriction enzymes, or hybridization.
2. Vector construction: Once the DNA sequence of interest has been isolated, it must be inserted into a vector, which is a small circular DNA molecule that can replicate independently in a host cell. Common vectors used in molecular cloning include plasmids and phages.
3. Transformation: The constructed vector is then introduced into a host cell, usually a bacterial or yeast cell, through a process called transformation. This can be done using various methods such as electroporation or chemical transformation.
4. Selection: After transformation, the host cells are grown in selective media that allow only those cells containing the vector to grow. This ensures that the DNA sequence of interest has been successfully cloned into the vector.
5. Amplification: Once the host cells have been selected, they can be grown in large quantities to amplify the number of copies of the cloned DNA sequence.

Molecular cloning is a powerful tool in molecular biology and has numerous applications, including the production of recombinant proteins, gene therapy, functional analysis of genes, and genetic engineering.

Flavins are a group of naturally occurring organic compounds that contain a characteristic isoalloxazine ring, which is a tricyclic aromatic structure. The most common and well-known flavin is flavin adenine dinucleotide (FAD), which plays a crucial role as a coenzyme in various biological oxidation-reduction reactions. FAD accepts electrons and hydrogens to form the reduced form, flavin adenine dinucleotide hydride (FADH2). Another important flavin is flavin mononucleotide (FMN), which is derived from FAD and functions similarly as a coenzyme. Flavins are yellow in color and can be found in various biological systems, including animals, plants, and microorganisms. They are involved in several metabolic pathways, such as the electron transport chain, where they contribute to energy production.

Peptide synthases are a group of enzymes that catalyze the formation of peptide bonds between specific amino acids to produce peptides or proteins. They are responsible for the biosynthesis of many natural products, including antibiotics, bacterial toxins, and immunomodulatory peptides.

Peptide synthases are large, complex enzymes that consist of multiple domains and modules, each of which is responsible for activating and condensing specific amino acids. The activation of amino acids involves the formation of an aminoacyl-adenylate intermediate, followed by transfer of the activated amino acid to a thiol group on the enzyme. The condensation of two activated amino acids results in the formation of a peptide bond and release of adenosine monophosphate (AMP) and pyrophosphate.

Peptide synthases are found in all three domains of life, but are most commonly associated with bacteria and fungi. They play important roles in the biosynthesis of many natural products that have therapeutic potential, making them targets for drug discovery and development.

Folate receptors (FRs) are a group of cell surface proteins that bind and transport folate (vitamin B9) into cells. The subtype referred to as "GPI-anchored" refers to the type of anchoring that these receptors have in the cell membrane.

GPI stands for glycosylphosphatidylinositol, which is a molecule that acts as an anchor for certain proteins in the cell membrane. GPI-anchored folate receptors are attached to the outer layer of the cell membrane through this GPI anchor, rather than being embedded within the membrane like many other proteins.

GPI-anchored folate receptors are found on various types of cells, including some cancer cells, and they play a role in the uptake of folate into those cells. Folate is an essential nutrient that plays a critical role in DNA synthesis and methylation, among other processes. Abnormalities in folate metabolism have been linked to various diseases, including cancer and neurological disorders.

Antineoplastic agents are a class of drugs used to treat malignant neoplasms or cancer. These agents work by inhibiting the growth and proliferation of cancer cells, either by killing them or preventing their division and replication. Antineoplastic agents can be classified based on their mechanism of action, such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, and targeted therapy agents.

Alkylating agents work by adding alkyl groups to DNA, which can cause cross-linking of DNA strands and ultimately lead to cell death. Antimetabolites interfere with the metabolic processes necessary for DNA synthesis and replication, while topoisomerase inhibitors prevent the relaxation of supercoiled DNA during replication. Mitotic inhibitors disrupt the normal functioning of the mitotic spindle, which is essential for cell division. Targeted therapy agents are designed to target specific molecular abnormalities in cancer cells, such as mutated oncogenes or dysregulated signaling pathways.

It's important to note that antineoplastic agents can also affect normal cells and tissues, leading to various side effects such as nausea, vomiting, hair loss, and myelosuppression (suppression of bone marrow function). Therefore, the use of these drugs requires careful monitoring and management of their potential adverse effects.

Molecular models are three-dimensional representations of molecular structures that are used in the field of molecular biology and chemistry to visualize and understand the spatial arrangement of atoms and bonds within a molecule. These models can be physical or computer-generated and allow researchers to study the shape, size, and behavior of molecules, which is crucial for understanding their function and interactions with other molecules.

Physical molecular models are often made up of balls (representing atoms) connected by rods or sticks (representing bonds). These models can be constructed manually using materials such as plastic or wooden balls and rods, or they can be created using 3D printing technology.

Computer-generated molecular models, on the other hand, are created using specialized software that allows researchers to visualize and manipulate molecular structures in three dimensions. These models can be used to simulate molecular interactions, predict molecular behavior, and design new drugs or chemicals with specific properties. Overall, molecular models play a critical role in advancing our understanding of molecular structures and their functions.

DCMP deaminase is an enzyme that catalyzes the deamination of deoxycytidine monophosphate (dCMP) to deoxyuridine monophosphate (dUMP). This reaction is a part of the pyrimidine nucleotide biosynthesis pathway. The enzyme's systematic name is "deoxycytidine monophosphate deaminase." It plays a crucial role in DNA synthesis and maintenance by providing the necessary precursor (dUMP) for thymidylate synthesis, which is essential for the production of thymidine triphosphate (dTTP), one of the four building blocks of DNA.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Folate Receptor 1 (FR-α or FOLR1) is a protein that is encoded by the folate receptor 1 gene in humans. It is a member of the folate receptor family, which are responsible for the transport of folate (vitamin B9) into cells. FR-α is primarily expressed in the epithelial cells of various organs, including the lungs, kidneys, and choroid plexus.

FR-α has a high affinity for folic acid and reduced folates, which it internalizes through receptor-mediated endocytosis. Once inside the cell, these molecules are converted to tetrahydrofolate (THF), an essential cofactor in various metabolic processes such as DNA synthesis, repair, and methylation.

In addition to its physiological role, FR-α has been implicated in several pathological conditions, including cancer. Many tumors, particularly ovarian and lung cancers, overexpress FR-α, making it an attractive target for targeted therapy using folate-conjugated drugs or radiolabeled folic acid for imaging and treatment.

Idoxuridine is an antiviral medication used primarily for the treatment of herpes simplex virus (HSV) infections of the eye, such as keratitis or dendritic ulcers. It works by interfering with the DNA replication of the virus, thereby inhibiting its ability to multiply and spread.

Idoxuridine is available as an ophthalmic solution (eye drops) and is typically applied directly to the affected eye every 1-2 hours while awake, for up to 2 weeks. Common side effects include local irritation, stinging, or burning upon application. Prolonged use of idoxuridine may lead to bacterial resistance or corneal toxicity, so it is important to follow your healthcare provider's instructions carefully when using this medication.

It is essential to note that idoxuridine is not commonly used today due to the development of more effective and less toxic antiviral agents for HSV infections.

Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.

Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.

Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.

In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

X-ray crystallography is a technique used in structural biology to determine the three-dimensional arrangement of atoms in a crystal lattice. In this method, a beam of X-rays is directed at a crystal and diffracts, or spreads out, into a pattern of spots called reflections. The intensity and angle of each reflection are measured and used to create an electron density map, which reveals the position and type of atoms in the crystal. This information can be used to determine the molecular structure of a compound, including its shape, size, and chemical bonds. X-ray crystallography is a powerful tool for understanding the structure and function of biological macromolecules such as proteins and nucleic acids.

The cell cycle is a series of events that take place in a cell leading to its division and duplication. It consists of four main phases: G1 phase, S phase, G2 phase, and M phase.

During the G1 phase, the cell grows in size and synthesizes mRNA and proteins in preparation for DNA replication. In the S phase, the cell's DNA is copied, resulting in two complete sets of chromosomes. During the G2 phase, the cell continues to grow and produces more proteins and organelles necessary for cell division.

The M phase is the final stage of the cell cycle and consists of mitosis (nuclear division) and cytokinesis (cytoplasmic division). Mitosis results in two genetically identical daughter nuclei, while cytokinesis divides the cytoplasm and creates two separate daughter cells.

The cell cycle is regulated by various checkpoints that ensure the proper completion of each phase before progressing to the next. These checkpoints help prevent errors in DNA replication and division, which can lead to mutations and cancer.

Molecular structure, in the context of biochemistry and molecular biology, refers to the arrangement and organization of atoms and chemical bonds within a molecule. It describes the three-dimensional layout of the constituent elements, including their spatial relationships, bond lengths, and angles. Understanding molecular structure is crucial for elucidating the functions and reactivities of biological macromolecules such as proteins, nucleic acids, lipids, and carbohydrates. Various experimental techniques, like X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM), are employed to determine molecular structures at atomic resolution, providing valuable insights into their biological roles and potential therapeutic targets.

Gene expression regulation, enzymologic refers to the biochemical processes and mechanisms that control the transcription and translation of specific genes into functional proteins or enzymes. This regulation is achieved through various enzymatic activities that can either activate or repress gene expression at different levels, such as chromatin remodeling, transcription factor activation, mRNA processing, and protein degradation.

Enzymologic regulation of gene expression involves the action of specific enzymes that catalyze chemical reactions involved in these processes. For example, histone-modifying enzymes can alter the structure of chromatin to make genes more or less accessible for transcription, while RNA polymerase and its associated factors are responsible for transcribing DNA into mRNA. Additionally, various enzymes are involved in post-transcriptional modifications of mRNA, such as splicing, capping, and tailing, which can affect the stability and translation of the transcript.

Overall, the enzymologic regulation of gene expression is a complex and dynamic process that allows cells to respond to changes in their environment and maintain proper physiological function.

Adenocarcinoma is a type of cancer that arises from glandular epithelial cells. These cells line the inside of many internal organs, including the breasts, prostate, colon, and lungs. Adenocarcinomas can occur in any of these organs, as well as in other locations where glands are present.

The term "adenocarcinoma" is used to describe a cancer that has features of glandular tissue, such as mucus-secreting cells or cells that produce hormones. These cancers often form glandular structures within the tumor mass and may produce mucus or other substances.

Adenocarcinomas are typically slow-growing and tend to spread (metastasize) to other parts of the body through the lymphatic system or bloodstream. They can be treated with surgery, radiation therapy, chemotherapy, targeted therapy, or a combination of these treatments. The prognosis for adenocarcinoma depends on several factors, including the location and stage of the cancer, as well as the patient's overall health and age.

E2F1 is a member of the E2F family of transcription factors, which are involved in the regulation of cell cycle progression and apoptosis (programmed cell death). Specifically, E2F1 plays a role as a transcriptional activator, binding to specific DNA sequences and promoting the expression of genes required for the G1/S transition of the cell cycle.

In more detail, E2F1 forms a complex with a retinoblastoma protein (pRb) in the G0 and early G1 phases of the cell cycle. When pRb is phosphorylated by cyclin-dependent kinases during the late G1 phase, E2F1 is released and can then bind to its target DNA sequences and activate transcription of genes involved in DNA replication and cell cycle progression.

However, if E2F1 is overexpressed or activated inappropriately, it can also promote apoptosis, making it a key player in both cell proliferation and cell death pathways. Dysregulation of E2F1 has been implicated in the development of various human cancers, including breast, lung, and prostate cancer.

"Drug design" is the process of creating and developing a new medication or therapeutic agent to treat or prevent a specific disease or condition. It involves identifying potential targets within the body, such as proteins or enzymes that are involved in the disease process, and then designing small molecules or biologics that can interact with these targets to produce a desired effect.

The drug design process typically involves several stages, including:

1. Target identification: Researchers identify a specific molecular target that is involved in the disease process.
2. Lead identification: Using computational methods and high-throughput screening techniques, researchers identify small molecules or biologics that can interact with the target.
3. Lead optimization: Researchers modify the chemical structure of the lead compound to improve its ability to interact with the target, as well as its safety and pharmacokinetic properties.
4. Preclinical testing: The optimized lead compound is tested in vitro (in a test tube or petri dish) and in vivo (in animals) to evaluate its safety and efficacy.
5. Clinical trials: If the preclinical testing is successful, the drug moves on to clinical trials in humans to further evaluate its safety and efficacy.

The ultimate goal of drug design is to create a new medication that is safe, effective, and can be used to improve the lives of patients with a specific disease or condition.

Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.

Catalysis is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst, which remains unchanged at the end of the reaction. A catalyst lowers the activation energy required for the reaction to occur, thereby allowing the reaction to proceed more quickly and efficiently. This can be particularly important in biological systems, where enzymes act as catalysts to speed up metabolic reactions that are essential for life.

Pyrimidine analogues Thymidylate synthase inhibitor Thymidine kinase Thymidine kinase in clinical chemistry Thymidylate kinase ... Thymidylate synthase is an enzyme of about 30 to 35 kDa in most species except in protozoan and plants where it exists as a ... Thymidylate synthase (TS) plays a crucial role in the early stages of DNA biosynthesis. DNA damage or deletion occur on a daily ... Thymidylate synthase is induced by a transcription factor LSF/TFCP2 and LSF is an oncogene in hepatocellular carcinoma. LSF and ...
Atomic Structure of Thymidylate Synthase: Target for Rational Drug Design. Hardy, L.W., Finer-Moore, J.S., Montfort, W. ... Invariant arginine 179, one of four arginines that are conserved in all thymidylate synthases (TS) and that bind the phosphate ... Invariant arginine 179, one of four arginines that are conserved in all thymidylate synthases (TS) and that bind the phosphate ... Refined Structures of Substrate-Bound and Phosphate-Bound Thymidylate Synthase from Lactobacillus Casei. Finer-Moore, J.S.,& ...
Protein target information for Thymidylate synthase (Pneumocystis carinii). Find diseases associated with this biological ...
Binding of the anticancer drug ZD1694 to E. coli thymidylate synthase: assessing specificity and affinity.. Rutenber, E.E., ... Thymidylate synthase (TS) catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) by 5, 10- ... BINDING OF THE ANTICANCER DRUG ZD1694 TO E. COLI THYMIDYLATE SYNTHASE: ASSESSING SPECIFICITY AND AFFINITY. *PDB DOI: https:// ... COLI THYMIDYLATE SYNTHASE: ASSESSING SPECIFICITY AND AFFINITY ... THYMIDYLATE SYNTHASE. A, B. 264. Escherichia coli. Mutation(s) ...
... a powerful inhibitor of thymidylate synthase, dihydrofolate reductase, and GARFT. Explore a compelling case of pemetrexeds ... Pemetrexed is an antimetabolic agent and is well-known as a potent inhibitor of thymidylate synthase (TS). It also inhibits ... Good Response to Pemetrexed after Treatment Failure with Another Thymidylate Synthase Inhibitor in Lung Adenocarcinoma: A Case ... Good Response to Pemetrexed after Treatment Failure with Another Thymidylate Synthase Inhibitor in Lung Adenocarcinoma: A Case ...
Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer. Br J Cancer. 2011;104:1594-601 ... Thymidylate synthase expression is closely associated with outcome in patients with pulmonary adenocarcinoma. Med Oncol. 2012; ... Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with ... Thymidylate synthase and dihydrofolate reductase expression in non-small cell lung carcinoma: the association with treatment ...
The dimer destabilizers cause a dimer-to-monomer equilibrium shift favoring the human thymidylate synthase monomer more ... Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth. ... Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth ... Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth ...
Inhibition of thymidylate synthase (TS) is an important mechanism of action of fluoropyrimidine antimetabolites. Thus, TS ... A naturally occurring variation in thymidylate synthase structure is associated with a reduced response to 5-fluoro-2- ... A naturally occurring variation in thymidylate synthase structure is associated with a reduced response to 5-fluoro-2- ... A naturally occurring variation in thymidylate synthase structure is associated with a reduced response to 5-fluoro-2- ...
Expression of thymidylate synthase is correlated with proliferative activity in non-small cell lung cancer (NSCLC). Lung Cancer ... High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil ... Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human ... Thymidylate synthase as an oncogene: a novel role for an essential DNA synthesis enzyme. Cancer Cell ...
Products are for research use only. Not for human use. We do not sell to patients ...
Cancer drugs such as 5-fluorouracil (5-FU) that target the enzyme thymidylate synthase (TS) have been and are still being ... This article belongs to the Special Issue Thymidylate synthase in biology and cancer treatment) ... Pharmacogenomics of thymidylate synthase in cancer treatment. Front. Biosci. (Landmark Ed) 2004, 9(4), 2484-2494. https://doi. ...
Scytek presents Thymidylate Synthase (5-FU Resistance Marker); Clone TS106 & TMS715 (Concentrate) - RA0328-C.1 ( Antibodies, ... Thymidylate Synthase (5-FU Resistance Marker); Clone TS106 & TMS715 (Concentrate). Species: Mouse. Immunogen: Recombinant human ... Specificity: This antibody recognizes a protein of 36kDa, identified as Thymidylate Synthase (TS) (EC 2.1.1.45). Status: RUO ... thymidylate synthase (TS106 & TMS715). Clone: TS106 & TMS715. Isotype: IgG1, kappa (TS106 & TMS715). Species Reactivity: Human ...
Role of an invariant lysine residue in folate binding on Escherichia coli thymidylate synthase: Calorimetric and ... Role of an invariant lysine residue in folate binding on Escherichia coli thymidylate synthase: Calorimetric and ...
STRUCTURAL BASIS FOR RECOGNITION OF POLYGLUTAMYL FOLATES BY THYMIDYLATE SYNTHASE ... STRUCTURAL BASIS FOR RECOGNITION OF POLYGLUTAMYL FOLATES BY THYMIDYLATE SYNTHASE Coordinates. PDB Format Method. X-RAY ... Kamb, A. et al., Structural basis for recognition of polyglutamyl folates by thymidylate synthase. Biochemistry (1992) Release ...
Thymidylate synthase. *2.4 PARP. *2.5 Dihydropteroate synthetase. *Farnesyltransferase. *2.6 GABA transaminase. *2.7 ...
Thymidylate synthase (TS) is a prominent drug target for different cancer types. However, the prolonged use of its classical ... Thymidylate synthase (TS) is a prominent drug target for different cancer types. However, the prolonged use of its classical ... The cPs were screened for the ability to inhibit recombinant human thymidylate synthase (hTS), and peptide 7 was found to act ... The cPs were screened for the ability to inhibit recombinant human thymidylate synthase (hTS), and peptide 7 was found to act ...
Thymidylate synthase (TS) is a target for pemetrexed and the prodrug 5-fluorouracil (5-FU) that inhibit the protein by binding ... Thymidylate synthase (TS) is a target for pemetrexed and the prodrug 5-fluorouracil (5-FU) that inhibit the protein by binding ... Optimization of Peptides That Target Human Thymidylate Synthase to Inhibit Ovarian Cancer Cell Growth. M. Pelà;SAXENA, PUNEET; ... Optimization of Peptides That Target Human Thymidylate Synthase to Inhibit Ovarian Cancer Cell Growth / M., Pelà; Saxena, ...
... Luca ... Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment ... Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment ...
Here we illustrate the ability of human CMV (HCMV) to stimulate cellular thymidylate synthase (TS) gene expression in quiescent ... Here we illustrate the ability of human CMV (HCMV) to stimulate cellular thymidylate synthase (TS) gene expression in quiescent ... Here we illustrate the ability of human CMV (HCMV) to stimulate cellular thymidylate synthase (TS) gene expression in quiescent ... Here we illustrate the ability of human CMV (HCMV) to stimulate cellular thymidylate synthase (TS) gene expression in quiescent ...
Replacement of Val3 in Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular Stability ... Replacement of Val3 in Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular Stability. *PDB DOI: https ... Replacement of Val3 in human thymidylate synthase affects its kinetic properties and intracellular stability .. Huang, X., ... Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal extension of approximately 27 amino acids that ...
The Clinical Significance of Thymidylate Synthase Expression in Human Papillomavirus - Related Oropharyngeal Squamous Carcinoma ... The Clinical Significance of Thymidylate Synthase Expression in Human Papillomavirus - Related Oropharyngeal Squamous Carcinoma ... The Clinical Significance of Thymidylate Synthase Expression in Human Papillomavirus - Related Oropharyngeal Squamous Carcinoma ... title = "The Clinical Significance of Thymidylate Synthase Expression in Human Papillomavirus - Related Oropharyngeal Squamous ...
Thymidylate synthase. 5-FU-stearic acid prodrug. Hyaluronic acid. Cisplatin. IVT + IVV. [57]. ... Thymidylate synthase. LY294002. PEG. 5-FU. IVT + IVV. [59]. Colorectal. ME. Thymidylate synthase. 5-FU. IVT + IVV. [60]. ...
Bifunctional dihydrofolate reductase-thymidylate synthase3-[2-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl) ... Bifunctional Dihydrofolate Reductase-thymidylate Synthase. Chemicals and Non-standard biopolymers (8 molecules) ...
Mechanistically, UCHL1 promoted PEM resistance in NSCLC by upregulating the expression of thymidylate synthase (TS), based on ... enzyme UCHL1 promotes resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase. ...
... uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal ... A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of ... A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of ... BACKGROUND: Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as ...
Background Thymidylate synthase (TS) and Topoisomerase We (Topo We) are significant. * Post author By careersfromscience ... Background Thymidylate synthase (TS) and Topoisomerase We (Topo We) are significant biomarkers in colorectal malignancy (CRC). ... These possess included intratumoral degrees of thymidylate synthase (TS), TP53 mutations, microsatellite instability, and ... Thymidylate synthase is vital for de novo DNA synthesis, by catalyzing the transformation of deoxy-uridine monophosphate (dUMP ...
GENETIC ANALYSIS OF THE DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE GENE FROM GEOGRAPHICALLY DIVERSE ISOLATES OF PLASMODIUM ... GENETIC ANALYSIS OF THE DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE GENE FROM GEOGRAPHICALLY DIVERSE ISOLATES OF PLASMODIUM ...
MSMEG_2670 MSMEG_2670 Thymidylate synthase (TS) (TSase) (EC 2.1.1.45). Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155) ...
Dive into the research topics of Molecular downstream events and induction of thymidylate synthase in mutant and wild-type p53 ... Molecular downstream events and induction of thymidylate synthase in mutant and wild-type p53 colon cancer cell lines after ... Inhibition of the key enzyme in DNA synthesis, thymidylate synthase (TS), by 5-fluorouracil (5-FU) and the novel antifolate ... Molecular downstream events and induction of thymidylate synthase in mutant and wild-type p53 colon cancer cell lines after ...
  • Thymidylate synthase (TS) (EC 2.1.1.45) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). (wikipedia.org)
  • Specificity: This antibody recognizes a protein of 36kDa, identified as Thymidylate Synthase (TS) (EC 2.1.1.45). (scytek.com)
  • Thymidylate synthase is an enzyme of about 30 to 35 kDa in most species except in protozoan and plants where it exists as a bifunctional enzyme that includes a dihydrofolate reductase domain. (wikipedia.org)
  • Cancer drugs such as 5-fluorouracil (5-FU) that target the enzyme thymidylate synthase (TS) have been and are still being widely used in cancer treatment, but as with other anti-cancer drugs, the majority of tumors do not respond to the treatment, whereas the patients still suffer drug-related toxicity. (imrpress.com)
  • Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. (unife.it)
  • The deubiquitinating enzyme UCHL1 promotes resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase. (bvsalud.org)
  • The following reaction is catalyzed by thymidylate synthase: 5,10-methylenetetrahydrofolate + dUMP ⇌ {\displaystyle \rightleftharpoons } dihydrofolate + dTMP By means of reductive methylation, deoxyuridine monophosphate (dUMP) and N5,N10-methylene tetrahydrofolate are together used to form dTMP, yielding dihydrofolate as a secondary product. (wikipedia.org)
  • Thymidylate synthase (TS) catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) by 5, 10-methylenetetrahydrofolate (CH2H4folate) to form deoxythymidine monophosphate (dTMP) and dihydrofolate (H2folate). (rcsb.org)
  • The phenotypes of single- (SKO) and double-knockout (DKO) lines of dihydrofolate reductase-thymidylate synthase (DHFR-TS) of bloodstream Trypanosoma brucei were evaluated in vitro and in vivo. (dundee.ac.uk)
  • Inhibition of thymidylate synthase (TS) is an important mechanism of action of fluoropyrimidine antimetabolites. (aspetjournals.org)
  • Mechanistically, UCHL1 promoted PEM resistance in NSCLC by upregulating the expression of thymidylate synthase (TS), based on reduced TS expression after UCHL1 inhibition and re-emergence of PEM resistance upon TS restoration. (bvsalud.org)
  • The cPs were screened for the ability to inhibit recombinant human thymidylate synthase (hTS), and peptide 7 was found to act as an allosteric inhibitor more potent than its parent open-chain peptide [Pro3]LR. (unipv.it)
  • Pemetrexed is an antimetabolic agent and is well-known as a potent inhibitor of thymidylate synthase (TS). (scirp.org)
  • The present study evaluated the prognostic value of the epidermal growth factor receptor (EGFR) mutation status, and excision repair cross-complementation group 1 (ERCC1) and thymidylate synthase (TS) expression following intercalated tyrosine kinase inhibitor (TKI) therapy and platinum- and pemetrexed-based chemotherapies (subsequent second-line treatment) for patients with adenocarcinoma non-small-cell lung cancer (AC-NSCLC). (medsci.org)
  • Several biomarkers have been used to predict treatment responses, such as the EGFR mutation status for targeted therapy or the excision repair cross-complementation group 1 (ERCC1) and thymidylate synthase (TS) expression for conventional chemotherapy [ 3 - 8 ]. (medsci.org)
  • We investigated the clinical significance of E2F1 gene expression in relation to its target genes, thymidylate synthase ( TS ) and Survivin , in case of non-small-cell lung cancer (NSCLC). (aacrjournals.org)
  • Here we illustrate the ability of human CMV (HCMV) to stimulate cellular thymidylate synthase (TS) gene expression in quiescent human embryonic lung fibroblasts. (elsevierpure.com)
  • A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer. (ox.ac.uk)
  • Thymidylate synthase is vital for de novo DNA synthesis, by catalyzing the transformation of deoxy-uridine monophosphate (dUMP) to deoxy-thymidine monophosphate (dTMP). (careersfromscience.org)
  • Thymidylate synthase (TS) is a prominent drug target for different cancer types. (unipv.it)
  • Thymidylate synthase (TS) is a target for pemetrexed and the prodrug 5-fluorouracil (5-FU) that inhibit the protein by binding at its active site. (unimore.it)
  • LSF and Thymidylate synthase plays significant role in Liver Cancer proliferation and progression and Drug resistance. (wikipedia.org)
  • Landis, D.M., Heindel, C.C. and Loeb, L.A. (2001) Creation and Characterization of 5-Fluorodeoxyuridine-Resistant Arg50 Loop Mutants of Human Thymidylate Synthase. (scirp.org)
  • A naturally occurring variation in thymidylate synthase structure is associated with a reduced response to 5-fluoro-2'-deoxyuridine in a human colon tumor cell line. (aspetjournals.org)
  • Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal extension of approximately 27 amino acids that is not present in bacterial TSs. (rcsb.org)
  • BACKGROUND: Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC). (ox.ac.uk)
  • Thymidylate synthase (TS) plays a crucial role in the early stages of DNA biosynthesis. (wikipedia.org)
  • ABSTRACT: Thymidylate synthase (TS) is a tumor-associated enzyme critical for DNA replication and main 5′-fluorouracil (5′-FU) target. (unipa.it)
  • 11. Thymidylate synthase inhibitors. (nih.gov)
  • Sulfadoxine resistance in human malaria parasite P. falciparum is determined by mutations in the dihydropteroate synthase gene and an additional factor associated with folate utilisation. (ajtmh.org)
  • TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase). (empr.com)
  • Quantitative measurement of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level in gastric cancer by real-time RT-PCR. (koreamed.org)
  • Sufficient levels of CH2-THF enhance the inhibition of the enzyme thymidylate synthase by the 5-FU metabolite FdUMP. (nih.gov)
  • Understanding the structural basis of species selective, stereospecific inhibition for Cryptosporidium and human thymidylate synthase. (cornell.edu)
  • The crystal structures of a deletion mutant of human thymidylate synthase (TS) and its ternary complex with dUMP and Tomudex have been determined at 2.0 A and 2.5 A resolution, respectively. (rcsb.org)
  • Crystal structure of a deletion mutant of human thymidylate synthase Delta (7-29) and its ternary complex with Tomudex and dUMP. (expasy.org)
  • Through its action dUTPase efficiently prevents uracil misincorporation into DNA and at the same time provides dUMP, the substrate for de novo thymidylate biosynthesis. (mdpi.com)
  • Induction of resistance to the multitargeted antifolate Pemetrexed (ALIMTA) in WiDr human colon cancer cells is associated with thymidylate synthase overexpression. (amsterdamumc.org)
  • One form 5,10 methylenetetrahydrofolate is the essential 1-carbon donor and reduced folate substrate for thymidylate synthase, the enzyme that catalyzes methylation of deoxyuridine5-monophosphate to deoxythymidine-5-monophosphate. (standardofcare.com)
  • A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer. (ox.ac.uk)
  • Thymidylate synthase (TS) plays a crucial role in the early stages of DNA biosynthesis. (wikipedia.org)
  • Using immunohistochemistry to evaluate thymidylate synthase protein levels, we found that the expression of thymidylate synthase in these mixed tumors roughly parallel that of squamous cell carcinoma, instead of falling in between squamous cell and adenocarcinoma. (njit.edu)
  • The thymidylate synthase (TS), an important target for many anticancer drugs, has been cloned from different species. (elsevierpure.com)
  • LSF and Thymidylate synthase plays significant role in Liver Cancer proliferation and progression and Drug resistance. (wikipedia.org)
  • The quantitation by radioimmunoassay of 2'-deoxyuridine 5'-triphosphate in extracts of thymidylate synthase-inhibited cells. (ox.ac.uk)
  • Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita. (cdc.gov)
  • The ETC, found in the inner membrane of the mitochondria, consists of four protein complexes commonly referred to as complexes I, II, III, and IV, along with two mobile electron carriers (ubiquinone or coenzyme Q [CoQ] and cytochrome c) and the ATP synthase complex [ 4 ]. (nih.gov)
  • BACKGROUND: Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC). (ox.ac.uk)
  • Patients with lower levels thymidylate synthase had better treatment outcomes with pemetrexed-based chemotherapy. (survivingmesothelioma.com)
  • Wahba NI, Khorsid O, Abo Elkasem F, Bahnassy A, Gaafer R. The Predictive Value of ERCC1, RRM1, and Thymidylate Synthase in Advanced Malignant Pleural Mesothelioma Patients Treated with Platinum-Based Chemotherapy. (survivingmesothelioma.com)
  • If a doctor wants to start chemotherapy with pemetrexed, they might want to test levels of thymidylate synthase in the patient. (survivingmesothelioma.com)