An enzyme catalyzing the formation of AMP from adenine and phosphoribosylpyrophosphate. It can act as a salvage enzyme for recycling of adenine into nucleic acids. EC 2.4.2.7.
Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.
An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.
The key substance in the biosynthesis of histidine, tryptophan, and purine and pyrimidine nucleotides.
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.
The short, submetacentric human chromosomes, called group E in the human chromosome classification. This group consists of chromosome pairs 16, 17, and 18.
An enzyme that catalyzes the formation of nicotinamide mononucleotide (NMN) from nicotinamide and 5-phosphoribosyl-1-pyrophosphate, the rate-limiting step in the biosynthesis of the NAD coenzyme. It is also known as a growth factor for early B-LYMPHOCYTES, or an ADIPOKINE with insulin-mimetic effects (visfatin).
Antibiotic substance produced by various Streptomyces species. It is an inhibitor of enzymatic activities that involve glutamine and is used as an antineoplastic and immunosuppressive agent.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
An inherited disorder transmitted as a sex-linked trait and caused by a deficiency of an enzyme of purine metabolism; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE. Affected individuals are normal in the first year of life and then develop psychomotor retardation, extrapyramidal movement disorders, progressive spasticity, and seizures. Self-destructive behaviors such as biting of fingers and lips are seen frequently. Intellectual impairment may also occur but is typically not severe. Elevation of uric acid in the serum leads to the development of renal calculi and gouty arthritis. (Menkes, Textbook of Child Neurology, 5th ed, pp127)
Pentosephosphates are monosaccharides, specifically pentoses, that have a phosphate group attached, playing crucial roles in carbohydrate metabolism, such as being intermediates in the pentose phosphate pathway and serving as precursors for nucleotide synthesis.
An enzyme that catalyzes the first step of the pathway for histidine biosynthesis in Salmonella typhimurium. ATP reacts reversibly with 5-phosphoribosyl-1-pyrophosphate to yield N-1-(5'-phosphoribosyl)-ATP and pyrophosphate. EC 2.4.2.17.
An enzyme that catalyzes the reaction between a purine nucleoside and orthophosphate to form a free purine plus ribose-5-phosphate. EC 2.4.2.1.
A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
An enzyme that catalyzes the formation of N-5'-phosphoribosylanthranilic acid from anthranilate and phosphoribosylpyrophosphate, the first step in tryptophan synthesis in E. coli. It exists in a complex with ANTHRANILATE SYNTHASE in bacteria. EC 2.4.2.18.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
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.
Identification of genetic carriers for a given trait.
Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
One of the early purine analogs showing antineoplastic activity. It functions as an antimetabolite and is easily incorporated into ribonucleic acids.
Inborn errors of purine-pyrimidine metabolism refer to genetic disorders resulting from defects in the enzymes responsible for the metabolic breakdown and synthesis of purines and pyrimidines, leading to the accumulation of toxic metabolites or deficiency of necessary nucleotides, causing various clinical manifestations such as neurological impairment, kidney problems, and developmental delays.
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
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.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Enzymes that catalyze the transfer of glucose from a nucleoside diphosphate glucose to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-.
The rate dynamics in chemical or physical systems.
Adenine nucleotides are molecules that consist of an adenine base attached to a ribose sugar and one, two, or three phosphate groups, including adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP), which play crucial roles in energy transfer and signaling processes within cells.
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).
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Established cell cultures that have the potential to propagate indefinitely.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Colorless, odorless crystals that are used extensively in research laboratories for the preparation of polyacrylamide gels for electrophoresis and in organic synthesis, and polymerization. Some of its polymers are used in sewage and wastewater treatment, permanent press fabrics, and as soil conditioning agents.
3-Carbamoyl-1-beta-D-ribofuranosyl pyridinium hydroxide-5'phosphate, inner salt. A nucleotide in which the nitrogenous base, nicotinamide, is in beta-N-glycosidic linkage with the C-1 position of D-ribose. Synonyms: Nicotinamide Ribonucleotide; NMN.
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 purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway.

Developmental changes in purine phosphoribosyltransferases in human and rat tissues. (1/221)

1. The hypoxanthine/guanine and adenine phosphoribosyltransferase activities in a wide variety of human tissues were studied during their growth and development from foetal life onward. A wide range of activities develop after birth, with especially high values in the central nervous system and testes. 2. Postnatal development of hypoxanthine/guanine phosphoribosyltransferase was also defined in the rat. Although there were increases in the central nervous system and testes, there was also a rise in activity in the liver, which was less marked in man. 3. A sensitive radiochemical assay method, using dTTP to inhibit 5'-nucleotidase activity, suitable for tissue extracts, was developed. 4. No definite evidence of the existence of tissue-specific isoenzymes of hypoxanthine/guanine or adenine phosphoribosyltransferase was found. Hypoxanthine/guanine phosphoribosyltransferase in testes, however, had a significantly different thermal-denaturation rate constant. 5. The findings are discussed in an attempt to relate activity of hypoxanthine/guanine phosphoribosyltransferase to biological function. Growth as well as some developmental changes appear to be related to increase in the activity of this enzyme.  (+info)

A novel signature mutation for oxidative damage resembles a mutational pattern found commonly in human cancers. (2/221)

To determine the types of mutations induced by oxidative damage, a kidney cell line with a heterozygous deficiency for the autosomal Aprt (adenine phosphoribosyltransferase) gene was tested for its mutagenic response to hydrogen peroxide. Aprt-deficient cells were selected and scored for loss of heterozygosity (LOH) for 11 microsatellite loci on mouse chromosome 8. On the basis of the LOH analysis, spontaneous mutants (n = 38) were distributed into four classes: apparent point mutation, mitotic recombination, chromosome loss, and large interstitial deletion. However, 9 of 20 (45%) hydrogen peroxide-induced mutants exhibited a novel class of mutations characterized by "discontinuous LOH" for one or more of the microsatellite loci. Interestingly, mutations resembling discontinuous LOH are commonly observed in a wide variety of human cancers. Our data suggest that discontinuous LOH is a signature mutational pattern for oxidative damage and further suggest that such genetic damage is widespread in cancer.  (+info)

Effect of interferon-gamma on purine catabolic and salvage enzyme activities in rats. (3/221)

To determine whether interferon-gamma affects rat purine catabolic and salvage enzyme activities, rats were injected with interferon-gamma (600000 U/kg, i.p.) and, similarly to a vehicle-injected control group, killed before or after injection at 6, 12, and 24 h. Organ homogenates were prepared and enzymatic reactions with substrates were carried out, after which the products were measured either chromatographically or spectrophotometrically. Western and Northern blotting also were performed. In contrast to the vehicle-injected rats, interferon-gamma-injected rats showed a significant rise in xanthine oxidoreductase activity in the liver, while enzyme activity was unchanged in the spleen, kidney, and lung. Western analysis of hepatic xanthine oxidoreductase showed an increased concentration of this protein 12 and 24 h after interferon-gamma injection. Northern analysis disclosed an enhanced mRNA expression coding for this enzyme, peaking 12 h after injection. Contrastingly, the activities of adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine guanine phosphoribosyltransferase, and adenine phosphoribosyltransferase were not affected by interferon-gamma in any organ tested. While interferon-gamma causes an increased hepatic biosynthesis of xanthine oxidoreductase, the physiologic role of this enzyme induction remains undetermined.  (+info)

Crystal structures of adenine phosphoribosyltransferase from Leishmania donovani. (4/221)

The enzyme adenine phosphoribosyltransferase (APRT) functions to salvage adenine by converting it to adenosine-5-monophosphate (AMP). APRT deficiency in humans is a well characterized inborn error of metabolism, and APRT may contribute to the indispensable nutritional role of purine salvage in protozoan parasites, all of which lack de novo purine biosynthesis. We determined crystal structures for APRT from Leishmania donovani in complex with the substrate adenine, the product AMP, and sulfate and citrate ions that appear to mimic the binding of phosphate moieties. Overall, these structures are very similar to each other, although the adenine and AMP complexes show different patterns of hydrogen-bonding to the base, and the active site pocket opens slightly to accommodate the larger AMP ligand. Whereas AMP adopts a single conformation, adenine binds in two mutually exclusive orientations: one orientation providing adenine-specific hydrogen bonds and the other apparently positioning adenine for the enzymatic reaction. The core of APRT is similar to that of other phosphoribosyltransferases, although the adenine-binding domain is quite different. A C-terminal extension, unique to Leishmania APRTs, extends an extensive dimer interface by wrapping around the partner molecule. The active site involves residues from both subunits of the dimer, indicating that dimerization is essential for catalysis.  (+info)

Mitotic recombination produces the majority of recessive fibroblast variants in heterozygous mice. (5/221)

Mice heterozygous at Aprt (adenine phosphoribosyltransferase) were used as a model to study in vivo loss of heterozygosity (LOH) in normal fibroblasts. Somatic cell variants that exhibited functional loss of the wild-type Aprt in vivo were recovered as APRT-deficient cell colonies after culturing in selection medium containing 2, 6-diaminopurine (DAP), an adenine analog that is toxic only to cells with APRT enzyme activity. DAP-resistant (DAP(r)) fibroblast variants were recovered at a median frequency of 12 x 10(-5) from individual ears from progeny of crosses between mouse strains 129/Sv and C3H/HeJ. The frequency of DAP(r) variants varied greatly among individual ears, suggesting that they preexisted in vivo and arose at various times during development. Polymorphic molecular markers and a cytological marker on the centromere of chromosome 8 made it possible to discriminate between each of six possible mechanistic pathways of LOH. The majority (about 80%) of the DAP(r) variants were a consequence of mitotic recombination. The prevalence of mitotic recombination in regions proximal to Aprt did not correlate with meiotic map distances. In particular, there was a higher than expected frequency of crossovers within the interval 59 cM to 67 cM. The high spontaneous frequency of Aprt LOH, mediated primarily by mitotic recombination, is fully consistent with our previous results with human peripheral T cells from individuals known to be heterozygous at APRT. Thus, this Aprt heterozygote mouse is a valid model for studying somatic mutagenesis and mitotic recombination in vivo.  (+info)

Enhanced amsacrine-induced mutagenesis in plateau-phase Chinese hamster ovary cells, with targeting of +1 frameshifts to free 3' ends of topoisomerase II cleavable complexes. (6/221)

Previous work showed that the DNA double-strand cleaving agents bleomycin and neocarzinostatin were more mutagenic in plateau-phase than in log-phase cells. To determine whether topoisomerase II poisons that produce double-strand breaks by trapping of cleavable complexes would, likewise, induce mutations specific to plateau-phase cells, aprt mutations induced by amsacrine in both log-phase and plateau-phase CHO cells were analyzed. The maximum aprt mutant frequencies obtained were 7 x 10(-6) after treatment with 0.02 microM amsacrine in log phase and 27 x 10(-6) after treatment with 1 microM amsacrine in plateau phase, compared with a spontaneous frequency of < 1 x 10(-6). Base substitutions dominated the spectrum of mutations in log-phase cells, but were much less prevalent in plateau-phase cells. Both spectra also included small deletions, insertions and duplications, as well as few large-scale deletions or rearrangements. About 5% of the log-phase mutants and 16% of the plateau-phase mutants were +1 frameshifts, and all but one of these were targeted to potential free 3' termini of cleavable complexes, as determined by mapping of cleavage sites in DNA treated with topoisomerase II plus amsacrine in vitro. Thus, these insertions may arise from templated extension of the exposed 3' terminus by a DNA polymerase, followed by resealing of the strand, as shown previously for acridine-induced frameshifts in T4 phage.  (+info)

Solid tissues removed from ATM homozygous deficient mice do not exhibit a mutator phenotype for second-step autosomal mutations. (7/221)

The presence of increased frequencies of blood-derived and solid tumors in ataxia-telangiectasia (A-T) patients, coupled with a role for the ATM (A-T mutation) protein in detecting specific forms of DNA damage, has led to the assumption of a mutator phenotype in A TM-deficient cells. Supporting this assumption are observations of increased rates of chromosomal aberrations and intrachromosomal homologous recombinational events in the cells of A-T patients. We have bred mice with knockout mutations for the selectable Aprt (adenine phosphoribosyltransferase) locus and the Atm locus to examine the frequency of second-step autosomal mutations in Atm-deficient cells. Two solid tissues were examined: (a) the ear, which yields predominately mesenchymal cells; and (b) the kidney, which yields predominately epithelial cells. We report here the lack of a mutator phenotype for inactivating autosomal mutations in solid tissues of the Atm-deficient mice.  (+info)

Localized Derepression on the Human Inactive X Chromosone in Mouse-Human Cell Hybrids. (8/221)

Evidence for derepression of the gene for hypoxanthine phosphoribosyltransferase (HPRT; IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) on the human inactive X chromosome was obtained in hybrids of mouse and human cells. The mouse cells lacked HPRT and were also deficient in adenine phosphoribosyltransferase (APRT; AMP: pyrophosphate phosphoribosyltransferase; EC2.4.2.7). The human female fibroblasts were HPRT-deficient as a consequence of a mutation on the active X but contained a normal HPRT gene on the inactive X. The two human X chromosomes were further distinguished by differences in morphology: the inactive X was morphologically normal while the active X included most of the long arm of autosome no. 1 translocated to the distal end of the X long arm. Forty-one hybrid clones were first isolated by selection for the presence of APRT; when these clones were selected for HPRT, six of them yielded derivatives having human HPRT with incidences of about 1 in 10-6 APRT-selected hybrid cells. The HPRT-positive derivatives contained a normal-appearing X chromosome indistinguishable from the inactive X of the parental human fibroblasts. The active X with the translocation was not found in any of the HPRT-positive hybrid cells. Human phosphoglycerokinase (ATP:3-phospho-D-glycerate 1-phosphotransferase. EC 2.7.2.3) and glucose-6-phosphate dehydrogenase (D-glucose 6-phosphate: NADP 1-oxidoreductase, EC 1.1.1.49), which are specified by X-chromosomal loci, were not detected in the hybrids expressing HPRT even though they contained an apparently intact X chromosome. The observations are most simply explained by the infrequent, stable derepression of inactive X chromosome segments that include the HPRT locus but not the phosphoglycerokinase and glucose-6-phosphate dehydrogenase loci.  (+info)

Adenine Phosphoribosyltransferase (APRT) is an enzyme that plays a crucial role in the metabolism of purines, specifically adenine, in the body. The enzyme catalyzes the conversion of adenine to AMP (adenosine monophosphate) by transferring a phosphoribosyl group from 5-phosphoribosyl-1-pyrophosphate (PRPP) to adenine.

Deficiency in APRT can lead to a rare genetic disorder known as Adenine Phosphoribosyltransferase Deficiency or APRT Deficiency. This condition results in the accumulation of 2,8-dihydroxyadenine (DHA) crystals in the renal tubules, which can cause kidney stones and chronic kidney disease. Proper diagnosis and management, including dietary modifications and medication, are essential to prevent complications associated with APRT Deficiency.

Pentosyltransferases are a group of enzymes that catalyze the transfer of a pentose (a sugar containing five carbon atoms) molecule from one compound to another. These enzymes play important roles in various biochemical pathways, including the biosynthesis of nucleotides, glycoproteins, and other complex carbohydrates.

One example of a pentosyltransferase is the enzyme that catalyzes the addition of a ribose sugar to form a glycosidic bond with a purine or pyrimidine base during the biosynthesis of nucleotides, which are the building blocks of DNA and RNA.

Another example is the enzyme that adds xylose residues to proteins during the formation of glycoproteins, which are proteins that contain covalently attached carbohydrate chains. These enzymes are essential for many biological processes and have been implicated in various diseases, including cancer and neurodegenerative disorders.

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme that plays a crucial role in the salvage pathway of nucleotide synthesis. This enzyme catalyzes the conversion of hypoxanthine and guanine to their respective nucleotides, inosine monophosphate (IMP) and guanosine monophosphate (GMP), by transferring the phosphoribosyl group from 5-phosphoribosyl-1 pyrophosphate (PRPP) to the purine bases.

HGPRT deficiency is a genetic disorder known as Lesch-Nyhan syndrome, which is characterized by mental retardation, self-mutilation, spasticity, and uric acid overproduction due to the accumulation of hypoxanthine and guanine. This disorder is caused by mutations in the HPRT1 gene, leading to a decrease or absence of HGPRT enzyme activity.

Adenine is a purine nucleotide base that is a fundamental component of DNA and RNA, the genetic material of living organisms. In DNA, adenine pairs with thymine via double hydrogen bonds, while in RNA, it pairs with uracil. Adenine is essential for the structure and function of nucleic acids, as well as for energy transfer reactions in cells through its role in the formation of adenosine triphosphate (ATP), the primary energy currency of the cell.

Hypoxanthine is not a medical condition but a purine base that is a component of many organic compounds, including nucleotides and nucleic acids, which are the building blocks of DNA and RNA. In the body, hypoxanthine is produced as a byproduct of normal cellular metabolism and is converted to xanthine and then uric acid, which is excreted in the urine.

However, abnormally high levels of hypoxanthine in the body can indicate tissue damage or disease. For example, during intense exercise or hypoxia (low oxygen levels), cells may break down ATP (adenosine triphosphate) rapidly, releasing large amounts of hypoxanthine. Similarly, in some genetic disorders such as Lesch-Nyhan syndrome, there is an accumulation of hypoxanthine due to a deficiency of the enzyme that converts it to xanthine. High levels of hypoxanthine can lead to the formation of kidney stones and other complications.

Phosphoribosyl Pyrophosphate (PRPP) is defined as a key intracellular nucleotide metabolite that plays an essential role in the biosynthesis of purine and pyrimidine nucleotides, which are the building blocks of DNA and RNA. PRPP is synthesized from ribose 5-phosphate and ATP by the enzyme PRPP synthase. It contributes a phosphoribosyl group in the conversion of purines and pyrimidines to their corresponding nucleotides, which are critical for various cellular processes such as DNA replication, repair, and gene expression. Abnormal levels of PRPP have been implicated in several genetic disorders, including Lesch-Nyhan syndrome and PRPP synthetase superactivity.

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.

Chromosomes are thread-like structures located in the nucleus of cells that contain most of the DNA present in cells. They come in pairs, with one set inherited from each parent. In humans, there are typically 23 pairs of chromosomes, for a total of 46 chromosomes.

Chromosomes 16-18 refer to the specific chromosomes that make up the 16th and 17th pairs in human cells. Chromosome 16 is an acrocentric chromosome, meaning it has a short arm (p arm) and a long arm (q arm), with the centromere located near the middle of the chromosome. It contains around 115 million base pairs of DNA and encodes approximately 1,100 genes.

Chromosome 17 is a metacentric chromosome, meaning it has a centromere located in the middle, dividing the chromosome into two arms of equal length. It contains around 81 million base pairs of DNA and encodes approximately 1,300 genes.

Chromosome 18 is a small acrocentric chromosome with a short arm (p arm) and a long arm (q arm), with the centromere located near the end of the short arm. It contains around 76 million base pairs of DNA and encodes approximately 1,200 genes.

Abnormalities in these chromosomes can lead to various genetic disorders, such as Edwards syndrome (trisomy 18), Patau syndrome (trisomy 13), and some forms of Down syndrome (translocation between chromosomes 14 and 21).

Nicotinamide phosphoribosyltransferase (NAMPT) is an enzyme that plays a crucial role in the metabolism of nicotinamide adenine dinucleotide (NAD+), which is a coenzyme found in all living cells and is involved in various cellular processes, including energy production, DNA repair, and gene expression. NAMPT catalyzes the conversion of nicotinamide (a form of vitamin B3) into nicotinamide mononucleotide (NMN), which is then converted into NAD+.

NAMPT has been identified as a key regulator of NAD+ levels in the body, and its activity is associated with various health benefits, such as improved insulin sensitivity, reduced inflammation, and increased lifespan. On the other hand, decreased NAMPT activity has been linked to several age-related diseases, including diabetes, neurodegenerative disorders, and cardiovascular disease. Therefore, NAMPT is an important target for developing therapies aimed at preventing or treating these conditions.

Azaserine is a antineoplastic and antibiotic agent. Its chemical name is O-diazoacetyl-L-serine. It is an analog of the amino acid serine, which inhibits the enzyme necessary for the synthesis of DNA and RNA, thus preventing the growth of cancer cells. Azaserine is used in research but not in clinical medicine due to its high toxicity.

Purines are heterocyclic aromatic organic compounds that consist of a pyrimidine ring fused to an imidazole ring. They are fundamental components of nucleotides, which are the building blocks of DNA and RNA. In the body, purines can be synthesized endogenously or obtained through dietary sources such as meat, seafood, and certain vegetables.

Once purines are metabolized, they are broken down into uric acid, which is excreted by the kidneys. Elevated levels of uric acid in the body can lead to the formation of uric acid crystals, resulting in conditions such as gout or kidney stones. Therefore, maintaining a balanced intake of purine-rich foods and ensuring proper kidney function are essential for overall health.

Lesch-Nyhan Syndrome is a rare X-linked recessive genetic disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This leads to an accumulation of purines, which can result in neurological symptoms and self-injurious behaviors.

The main features of Lesch-Nyhan Syndrome include:

1. Neurological symptoms: These may include delayed development, choreoathetosis (involuntary movements), spasticity, and dystonia (sustained muscle contractions).
2. Self-injurious behaviors: Affected individuals often bite their lips, fingers, and inside of their cheeks, causing significant tissue damage.
3. Intellectual disability: Most individuals with Lesch-Nyhan Syndrome have moderate to severe intellectual disability.
4. Speech and language difficulties: Many affected individuals have difficulty speaking and understanding language.
5. Kidney problems: The accumulation of purines can lead to kidney stones and kidney failure in some cases.
6. Hyperuricemia: Elevated levels of uric acid in the blood (hyperuricemia) are a hallmark of Lesch-Nyhan Syndrome, which can lead to gout and joint damage.

Lesch-Nyhan Syndrome is typically diagnosed through genetic testing and enzyme assays. There is no cure for the disorder, but treatments may include medications to manage symptoms, behavioral interventions, and physical therapy.

Pentose phosphates are monosaccharides that contain five carbon atoms and one phosphate group. They play a crucial role in various metabolic pathways, including the pentose phosphate pathway (PPP), which is a major source of NADPH and ribose-5-phosphate for the synthesis of nucleotides.

The pentose phosphate pathway involves two main phases: the oxidative phase and the non-oxidative phase. In the oxidative phase, glucose-6-phosphate is converted to ribulose-5-phosphate, producing NADPH and CO2 as byproducts. Ribulose-5-phosphate can then be further metabolized in the non-oxidative phase to produce other pentose phosphates or converted back to glucose-6-phosphate through a series of reactions.

Pentose phosphates are also important intermediates in the synthesis of nucleotides, coenzymes, and other metabolites. Abnormalities in pentose phosphate pathway enzymes can lead to various metabolic disorders, such as defects in erythrocyte function and increased susceptibility to oxidative stress.

ATP phosphoribosyltransferase (ATP-PRT, or adenine phosphoribosyltransferase) is an enzyme involved in the purine nucleotide biosynthesis pathway. The enzyme catalyzes the conversion of ATP and 5-phosphoribosyl-1-pyrophosphate (PRPP) to adenosine monophosphate (AMP) and pyrophosphate (PPi). This reaction is part of the salvage pathway, which recycles purines by converting free purine bases back into nucleotides. A deficiency in ATP-PRT can lead to a rare genetic disorder known as adenine phosphoribosyltransferase deficiency or APRT deficiency, which is characterized by the accumulation of 2,8-dihydroxyadenine crystals in the renal tubules, resulting in kidney stones and potential kidney damage.

Purine-nucleoside phosphorylase (PNP) is an enzyme that plays a crucial role in the metabolism of purines, which are essential components of nucleic acids (DNA and RNA). The medical definition of 'Purine-Nucleoside Phosphorylase' refers to the physiological function of this enzyme in the human body.

PNP is responsible for catalyzing the phosphorolytic cleavage of purine nucleosides, such as inosine and guanosine, into their respective purine bases (hypoxanthine and guanine) and ribose-1-phosphate. This reaction is essential for the recycling and salvage of purine bases, allowing the body to conserve energy and resources needed for de novo purine biosynthesis.

In a clinical or medical context, deficiencies in PNP activity can lead to serious consequences, particularly affecting the immune system and the nervous system. A genetic disorder called Purine-Nucleoside Phosphorylase Deficiency (PNP Deficiency) is characterized by significantly reduced or absent PNP enzyme activity, leading to an accumulation of toxic purine nucleosides and deoxypurine nucleosides. This accumulation can cause severe combined immunodeficiency (SCID), neurological impairments, and other complications, making it a critical area of study in medical research.

I'm sorry for any confusion, but "Carcinoma, Ehrlich Tumor" is not a recognized medical term or a valid medical definition. The term "Ehrlich tumor" is sometimes used to refer to a type of transplantable tumor that was first developed by the German physician Paul Ehrlich in the early 20th century for cancer research purposes. However, it's important to note that this type of tumor is not a naturally occurring cancer and is typically used only in laboratory experiments.

Carcinoma, on the other hand, is a medical term that refers to a type of cancer that starts in cells that line the inner or outer surfaces of organs. Carcinomas can develop in various parts of the body, including the lungs, breasts, colon, and skin.

If you have any specific questions about cancer or a particular medical condition, I would be happy to try to help answer them for you.

Adenosine monophosphate (AMP) is a nucleotide that is the monophosphate ester of adenosine, consisting of the nitrogenous base adenine attached to the 1' carbon atom of ribose via a β-N9-glycosidic bond, which in turn is esterified to a phosphate group. It is an important molecule in biological systems as it plays a key role in cellular energy transfer and storage, serving as a precursor to other nucleotides such as ADP and ATP. AMP is also involved in various signaling pathways and can act as a neurotransmitter in the central nervous system.

Anthranilate phosphoribosyltransferase is an enzyme involved in the metabolism of tryptophan, an essential amino acid. This enzyme catalyzes the conversion of anthranilic acid to 1-(o-amino phenyl)phosphoric acid, which is a critical step in the biosynthesis of the aromatic compound known as quinoline.

The reaction catalyzed by anthranilate phosphoribosyltransferase involves the transfer of a phosphoribosyl group from phosphoribosyl pyrophosphate (PRPP) to anthranilic acid, resulting in the formation of 1-(o-amino phenyl)phosphoric acid and pyrophosphate. This reaction is an important part of the tryptophan degradation pathway, which helps regulate the levels of this essential amino acid in the body.

Deficiencies or mutations in anthranilate phosphoribosyltransferase can lead to various metabolic disorders, including a rare genetic condition known as autosomal recessive alkaptonuria (ARA). ARA is characterized by the accumulation of homogentisic acid and its oxidation product, melanin, in various tissues, leading to joint stiffness, darkened skin, and other symptoms.

Cricetinae is a subfamily of rodents that includes hamsters, gerbils, and relatives. These small mammals are characterized by having short limbs, compact bodies, and cheek pouches for storing food. They are native to various parts of the world, particularly in Europe, Asia, and Africa. Some species are popular pets due to their small size, easy care, and friendly nature. In a medical context, understanding the biology and behavior of Cricetinae species can be important for individuals who keep them as pets or for researchers studying their physiology.

Nucleotides are the basic structural units of nucleic acids, such as DNA and RNA. They consist of a nitrogenous base (adenine, guanine, cytosine, thymine or uracil), a pentose sugar (ribose in RNA and deoxyribose in DNA) and one to three phosphate groups. Nucleotides are linked together by phosphodiester bonds between the sugar of one nucleotide and the phosphate group of another, forming long chains known as polynucleotides. The sequence of these nucleotides determines the genetic information carried in DNA and RNA, which is essential for the functioning, reproduction and survival of all living organisms.

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.

Heterozygote detection is a method used in genetics to identify individuals who carry one normal and one mutated copy of a gene. These individuals are known as heterozygotes and they do not typically show symptoms of the genetic disorder associated with the mutation, but they can pass the mutated gene on to their offspring, who may then be affected.

Heterozygote detection is often used in genetic counseling and screening programs for recessive disorders such as cystic fibrosis or sickle cell anemia. By identifying heterozygotes, individuals can be informed of their carrier status and the potential risks to their offspring. This information can help them make informed decisions about family planning and reproductive options.

Various methods can be used for heterozygote detection, including polymerase chain reaction (PCR) based tests, DNA sequencing, and genetic linkage analysis. The choice of method depends on the specific gene or mutation being tested, as well as the availability and cost of the testing technology.

I'm sorry for any confusion, but "hybrid cells" is not a standard medical term with a widely accepted or specific definition in the field of medicine. The term "hybrid" is used in various scientific and medical contexts to describe combinations or mixtures of different elements, such as hybridoma cells (a type of fusion cell used in research, created by combining a B cell and a tumor cell) or hybridization (in genetics, the process of combining DNA from two different sources).

Without more specific context, it's difficult to provide an accurate medical definition for "hybrid cells." If you could provide more information about the context in which this term was used, I would be happy to help you further!

A gene is a specific sequence of nucleotides in DNA that carries genetic information. Genes are the fundamental units of heredity and are responsible for the development and function of all living organisms. They code for proteins or RNA molecules, which carry out various functions within cells and are essential for the structure, function, and regulation of the body's tissues and organs.

Each gene has a specific location on a chromosome, and each person inherits two copies of every gene, one from each parent. Variations in the sequence of nucleotides in a gene can lead to differences in traits between individuals, including physical characteristics, susceptibility to disease, and responses to environmental factors.

Medical genetics is the study of genes and their role in health and disease. It involves understanding how genes contribute to the development and progression of various medical conditions, as well as identifying genetic risk factors and developing strategies for prevention, diagnosis, and treatment.

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.

Azaguanine is a type of antimetabolite drug that is used in medical research and treatment. It is a purine analogue, which means it has a similar chemical structure to the natural purine bases adenine and guanine, which are building blocks of DNA and RNA. Azaguanine can be incorporated into the genetic material of cells, interfering with their normal function and replication. It is used in research to study the effects of such interference on cell growth and development.

In clinical medicine, azaguanine has been used as an anticancer drug, although it is not widely used today due to its toxicity and the availability of more effective treatments. It may also have some activity against certain types of parasitic infections, such as leishmaniasis and malaria.

It's important to note that azaguanine is not a commonly used medication and its use should be under the supervision of a medical professional with experience in its administration and management of potential side effects.

Inborn errors of purine-pyrimidine metabolism refer to genetic disorders that result in dysfunctional enzymes involved in the metabolic pathways of purines and pyrimidines. These are essential components of nucleotides, which in turn are building blocks of DNA and RNA.

Inherited as autosomal recessive or X-linked recessive traits, these disorders can lead to an accumulation of toxic metabolites, a deficiency of necessary compounds, or both. Clinical features vary widely depending on the specific enzyme defect but may include neurologic symptoms, kidney problems, gout, and/or immunodeficiency.

Examples of such disorders include Lesch-Nyhan syndrome (deficiency of hypoxanthine-guanine phosphoribosyltransferase), adenosine deaminase deficiency (leading to severe combined immunodeficiency), and orotic aciduria (due to defects in pyrimidine metabolism). Early diagnosis and management are crucial to improve outcomes.

"Cricetulus" is a genus of rodents that includes several species of hamsters. These small, burrowing animals are native to Asia and have a body length of about 8-15 centimeters, with a tail that is usually shorter than the body. They are characterized by their large cheek pouches, which they use to store food. Some common species in this genus include the Chinese hamster (Cricetulus griseus) and the Daurian hamster (Cricetulus dauuricus). These animals are often kept as pets or used in laboratory research.

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.

Southern blotting is a type of membrane-based blotting technique that is used in molecular biology to detect and locate specific DNA sequences within a DNA sample. This technique is named after its inventor, Edward M. Southern.

In Southern blotting, the DNA sample is first digested with one or more restriction enzymes, which cut the DNA at specific recognition sites. The resulting DNA fragments are then separated based on their size by gel electrophoresis. After separation, the DNA fragments are denatured to convert them into single-stranded DNA and transferred onto a nitrocellulose or nylon membrane.

Once the DNA has been transferred to the membrane, it is hybridized with a labeled probe that is complementary to the sequence of interest. The probe can be labeled with radioactive isotopes, fluorescent dyes, or chemiluminescent compounds. After hybridization, the membrane is washed to remove any unbound probe and then exposed to X-ray film (in the case of radioactive probes) or scanned (in the case of non-radioactive probes) to detect the location of the labeled probe on the membrane.

The position of the labeled probe on the membrane corresponds to the location of the specific DNA sequence within the original DNA sample. Southern blotting is a powerful tool for identifying and characterizing specific DNA sequences, such as those associated with genetic diseases or gene regulation.

Glucosyltransferases (GTs) are a group of enzymes that catalyze the transfer of a glucose molecule from an activated donor to an acceptor molecule, resulting in the formation of a glycosidic bond. These enzymes play crucial roles in various biological processes, including the biosynthesis of complex carbohydrates, cell wall synthesis, and protein glycosylation. In some cases, GTs can also contribute to bacterial pathogenesis by facilitating the attachment of bacteria to host tissues through the formation of glucans, which are polymers of glucose molecules.

GTs can be classified into several families based on their sequence similarities and catalytic mechanisms. The donor substrates for GTs are typically activated sugars such as UDP-glucose, TDP-glucose, or GDP-glucose, which serve as the source of the glucose moiety that is transferred to the acceptor molecule. The acceptor can be a wide range of molecules, including other sugars, proteins, lipids, or small molecules.

In the context of human health and disease, GTs have been implicated in various pathological conditions, such as cancer, inflammation, and microbial infections. For example, some GTs can modify proteins on the surface of cancer cells, leading to increased cell proliferation, migration, and invasion. Additionally, GTs can contribute to bacterial resistance to antibiotics by modifying the structure of bacterial cell walls or by producing biofilms that protect bacteria from host immune responses and antimicrobial agents.

Overall, Glucosyltransferases are essential enzymes involved in various biological processes, and their dysregulation has been associated with several human diseases. Therefore, understanding the structure, function, and regulation of GTs is crucial for developing novel therapeutic strategies to target these enzymes and treat related pathological conditions.

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.

Adenine nucleotides are molecules that consist of a nitrogenous base called adenine, which is linked to a sugar molecule (ribose in the case of adenosine monophosphate or AMP, and deoxyribose in the case of adenosine diphosphate or ADP and adenosine triphosphate or ATP) and one, two, or three phosphate groups. These molecules play a crucial role in energy transfer and metabolism within cells.

AMP contains one phosphate group, while ADP contains two phosphate groups, and ATP contains three phosphate groups. When a phosphate group is removed from ATP, energy is released, which can be used to power various cellular processes such as muscle contraction, nerve impulse transmission, and protein synthesis. The reverse reaction, in which a phosphate group is added back to ADP or AMP to form ATP, requires energy input and often involves the breakdown of nutrients such as glucose or fatty acids.

In addition to their role in energy metabolism, adenine nucleotides also serve as precursors for other important molecules, including DNA and RNA, coenzymes, and signaling molecules.

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.

CHO cells, or Chinese Hamster Ovary cells, are a type of immortalized cell line that are commonly used in scientific research and biotechnology. They were originally derived from the ovaries of a female Chinese hamster (Cricetulus griseus) in the 1950s.

CHO cells have several characteristics that make them useful for laboratory experiments. They can grow and divide indefinitely under appropriate conditions, which allows researchers to culture large quantities of them for study. Additionally, CHO cells are capable of expressing high levels of recombinant proteins, making them a popular choice for the production of therapeutic drugs, vaccines, and other biologics.

In particular, CHO cells have become a workhorse in the field of biotherapeutics, with many approved monoclonal antibody-based therapies being produced using these cells. The ability to genetically modify CHO cells through various methods has further expanded their utility in research and industrial applications.

It is important to note that while CHO cells are widely used in scientific research, they may not always accurately represent human cell behavior or respond to drugs and other compounds in the same way as human cells do. Therefore, results obtained using CHO cells should be validated in more relevant systems when possible.

Erythrocytes, also known as red blood cells (RBCs), are the most common type of blood cell in circulating blood in mammals. They are responsible for transporting oxygen from the lungs to the body's tissues and carbon dioxide from the tissues to the lungs.

Erythrocytes are formed in the bone marrow and have a biconcave shape, which allows them to fold and bend easily as they pass through narrow blood vessels. They do not have a nucleus or mitochondria, which makes them more flexible but also limits their ability to reproduce or repair themselves.

In humans, erythrocytes are typically disc-shaped and measure about 7 micrometers in diameter. They contain the protein hemoglobin, which binds to oxygen and gives blood its red color. The lifespan of an erythrocyte is approximately 120 days, after which it is broken down in the liver and spleen.

Abnormalities in erythrocyte count or function can lead to various medical conditions, such as anemia, polycythemia, and sickle cell disease.

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.

An allele is a variant form of a gene that is located at a specific position on a specific chromosome. Alleles are alternative forms of the same gene that arise by mutation and are found at the same locus or position on homologous chromosomes.

Each person typically inherits two copies of each gene, one from each parent. If the two alleles are identical, a person is said to be homozygous for that trait. If the alleles are different, the person is heterozygous.

For example, the ABO blood group system has three alleles, A, B, and O, which determine a person's blood type. If a person inherits two A alleles, they will have type A blood; if they inherit one A and one B allele, they will have type AB blood; if they inherit two B alleles, they will have type B blood; and if they inherit two O alleles, they will have type O blood.

Alleles can also influence traits such as eye color, hair color, height, and other physical characteristics. Some alleles are dominant, meaning that only one copy of the allele is needed to express the trait, while others are recessive, meaning that two copies of the allele are needed to express the trait.

Acrylamides are a type of chemical that can form in some foods during high-temperature cooking processes, such as frying, roasting, and baking. They are created when certain amino acids (asparagine) and sugars in the food react together at temperatures above 120°C (248°F). This reaction is known as the Maillard reaction.

Acrylamides have been classified as a probable human carcinogen by the International Agency for Research on Cancer (IARC), based on studies in animals. However, more research is needed to fully understand the potential health risks associated with acrylamide exposure from food.

Public health organizations recommend limiting acrylamide intake by following some cooking practices such as:

* Avoiding overcooking or burning foods
* Soaking potatoes (which are high in asparagine) in water before frying to reduce the formation of acrylamides
* Choosing raw, unprocessed, or minimally processed foods when possible.

Nicotinamide mononucleotide (NMN) is a bioactive nucleotide that is found in various cells and tissues within the human body. It is a crucial intermediate in the biosynthetic pathway of nicotinamide adenine dinucleotide (NAD+), which is an essential coenzyme involved in numerous cellular processes, including energy metabolism, DNA repair, and gene expression.

NMN can be synthesized within the body from nicotinamide or niacin, and it can also be obtained through dietary sources such as milk, fruits, and vegetables. In recent years, NMN has gained attention in the scientific community for its potential anti-aging effects, as studies have suggested that supplementation with NMN may help to restore NAD+ levels and improve various age-related physiological declines. However, more research is needed to fully understand the therapeutic potential of NMN and its mechanisms of action in humans.

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.

Hypoxanthine is a purine derivative and an intermediate in the metabolic pathways of nucleotide degradation, specifically adenosine to uric acid in humans. It is formed from the oxidation of xanthine by the enzyme xanthine oxidase. In the body, hypoxanthine is converted to xanthine and then to uric acid, which is excreted in the urine. Increased levels of hypoxanthine in the body can be indicative of various pathological conditions, including tissue hypoxia, ischemia, and necrosis.

"Adenine phosphoribosyltransferase isoforms of Arabidopsis and their potential contributions to adenine and cytokinin metabolism ... Adenine phosphoribosyltransferase (APRTase) is an enzyme encoded by the APRT gene, found in humans on chromosome 16. It is part ... Adenine+phosphoribosyltransferase at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Human APRT genome ... Takeuchi H, Kaneko Y, Fujita J, Yoshida O (Apr 1993). "A case of a compound heterozygote for adenine phosphoribosyltransferase ...
... is an autosomal recessive metabolic disorder associated with a mutation in the ... Adenine phosphoribosyltransferase deficiency at NIH's Office of Rare Diseases (Articles with short description, Short ... Patients with the disease deficiency lack the enzyme adenine phosphoribosyltransferase and therefore have difficulties breaking ... "Adenine phosphoribosyltransferase(APRT) deficiency" (Free full text). Nippon Rinsho. Japanese Journal of Clinical Medicine. 54 ...
... adenine phosphoribosyltransferase. It is also used to treat kidney stones caused by deficient activity of adenine ... hypoxanthine-guanine phosphoribosyltransferase, including Lesch-Nyhan syndrome; glucose 6-phosphatase including glycogen ... phosphoribosyltransferase. Allopurinol was also commonly used to treat tumor lysis syndrome in chemotherapeutic treatments, as ...
People affected by adenine phosphoribosyltransferase deficiency may produce 2,8-dihydroxyadenine stones, alkaptonurics produce ... Kamatani N (December 1996). "[Adenine phosphoribosyltransferase(APRT) deficiency]". Nihon Rinsho. Japanese Journal of Clinical ...
The enzyme adenine phosphoribosyltransferase (APRT) salvages adenine. The enzyme hypoxanthine-guanine phosphoribosyltransferase ... Both adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), which is the first compound in the ... Hyperuricemia and Lesch-Nyhan syndrome by the loss of hypoxanthine-guanine phosphoribosyltransferase. Different types of cancer ...
For example, adenine + PRPP --> AMP + PPi. This reaction requires the enzyme adenine phosphoribosyltransferase. Free guanine is ... Adenine and guanine are the two nucleotides classified as purines. In purine synthesis, PRPP is turned into inosine ... Lesch-Nyhan syndrome is caused by a deficiency in hypoxanthine-guanine phosphoribosyltransferase or HGPRT, the enzyme that ... salvaged in the same way except it requires hypoxanthine-guanine phosphoribosyltransferase. Defects in purine catabolism can ...
Schaff, Dennis A. (1994). "The adenine phosphoribosyltransferase (APRT) selectable marker system". Plant Science. Elsevier BV. ... adenine phosphoribosyltransferase) genes. Therefore, knockouts or mutants for APT, which are resistant to 2-FA, can be selected ... "Mutants of Saccharomyces cerevisiae deficient in adenine phosphoribosyltransferase". Mutation Research/Fundamental and ... 2-Fluoroadenine (2-FA) is a toxic adenine antimetabolite which can be used in laboratory biological research for ...
"DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells". Proceedings of the National Academy ...
A Saccharomyces cerevisiae gene encoding a potential adenine phosphoribosyltransferase Yuryev A, and Corden JL. Yeast 1994;10 ( ...
"Structural Complexes of Human Adenine Phosphoribosyltransferase Reveal Novel Features of the APRT Catalytic Mechanism". Journal ... Decreased levels of hypoxanthine guanine phosphoribosyl transferase (HGPRT) causes this accumulation, as PRPP is a substrate ... Salmonella typhimurium nicotinate phosphoribosyltransferase". Journal of Biological Chemistry. 268 (34): 26004-26010. doi: ... with the first step being N-alkylation of anthranilic acid catalysed by the enzyme anthranilate phosphoribosyltransferase. ...
There are two types of phosphoribosyltransferases: adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine ... Phosphoribosyltransferases add activated ribose-5-phosphate (Phosphoribosyl pyrophosphate, PRPP) to bases, creating nucleoside ... Nicotinate salvage is the process of regenerating nicotinamide adenine dinucleotide from nicotinic acid. This pathway is ... "Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells ...
... is excreted in the urine because of a deficiency in the adenine salvage enzyme adenine phosphoribosyltransferase. The defect is ... 2,8-Dihydroxyadenine is a derivative of adenine which accumulates in 2,8 dihydroxy-adenine urolithiasis. The poorly soluble ... "Identification of two novel mutations in adenine phosphoribosyltransferase gene in patients with 2,8-dihydroxyadenine ...
Cancer cells are known to become resistant to DAP by losing their adenine phosphoribosyltransferase (APRT) function, a process ... 6-diaminopurine and 6-methylpurine that affect adenine phosphoribosyltransferase in Escherichia coli K-12]". Genetika. 13 (10 ... As the Z base, it is found instead of adenine (A) in the genetic material of some bacteriophage viruses. In August 2011, a ... 2-aminoadenine is an adenine substituting for a base in S-2L cyanophage DNA. Nature. 1977 Nov 24;270(5635):369-70. Jacinta ...
Examples include: adenine phosphoribosyltransferase hypoxanthine-guanine phosphoribosyltransferase pertussis toxin poly ADP ...
These enzymes found in the glycosome to help with synthesis are guanine and adenine phosphoribosyl transferase, hypoxanthine, ...
Adenine phosphoribosyltransferase Hypoxanthine-guanine phosphoribosyltransferase Orotate phosphoribosyltransferase Quinolinate ... A phosphoribosyltransferase is a type of transferase enzyme. Types include: ... phosphoribosyltransferase Uracil phosphoribosyltransferase v t e (Transferases, All stub articles, Enzyme stubs). ...
... may refer to: Adenine phosphoribosyltransferase, an enzyme Hypoxanthine phosphoribosyltransferase This ...
... may refer to: Adenine phosphoribosyltransferase, an enzyme Adenine phosphoribosyltransferase deficiency, a genetic and ...
... adenine) phosphoribosyltransferase, nicotinate-nucleotide:dimethylbenzimidazole phospho-D-ribosyltransferase, and nicotinate ... In enzymology, a nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase (EC 2.4.2.21) is an enzyme that ... Other names in common use include CobT, nicotinate mononucleotide-dimethylbenzimidazole phosphoribosyltransferase, nicotinate ... 6-dimethylbenzimidazole phosphoribosyltransferase responsible for the synthesis of N1-(5-phospho-alpha-D-ribosyl)-5,6- ...
... adenine phosphoribosyltransferase EC 2.4.2.8: hypoxanthine phosphoribosyltransferase EC 2.4.2.9: uracil ... orotate phosphoribosyltransferase EC 2.4.2.11: now EC 6.3.4.21 nicotinate phosphoribosyltransferase EC 2.4.2.12: nicotinamide ... ATP phosphoribosyltransferase EC 2.4.2.18: anthranilate phosphoribosyltransferase EC 2.4.2.19: nicotinate-nucleotide ... nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase EC 2.4.2.22: xanthine phosphoribosyltransferase EC 2.4. ...
... adenine phosphoribosyltransferase MeSH D08.811.913.400.725.115 - adp ribose transferases MeSH D08.811.913.400.725.115.180 - ... anthranilate phosphoribosyltransferase MeSH D08.811.913.400.725.200 - ATP phosphoribosyltransferase MeSH D08.811.913.400. ... 725.450 - hypoxanthine phosphoribosyltransferase MeSH D08.811.913.400.725.700 - orotate phosphoribosyltransferase MeSH D08.811. ... flavin-adenine dinucleotide MeSH D08.211.474.650.500 - flavin mononucleotide MeSH D08.211.790.249 - g(m2) activator protein ...
... thumb club foot syndrome Adducted thumb syndrome recessive form Adducted thumbs Dundar type Adenine phosphoribosyltransferase ...
... adenine phosphoribosyltransferases, and guanine phosphoribosyltransferases. The human subjects experienced increases in ...
Their relationship to hypoxanthine and adenine phosphoribosyltransfer activities". J. Biol. Chem. 245 (10): 2605-11. PMID ... In enzymology, a xanthine phosphoribosyltransferase (EC 2.4.2.22) is an enzyme that catalyzes the chemical reaction XMP + ... Other names in common use include Xan phosphoribosyltransferase, xanthosine 5'-phosphate pyrophosphorylase, xanthylate ...
The intracellular form of this protein (iNAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) ... Nicotinamide phosphoribosyltransferase (NAmPRTase or NAMPT), formerly known as pre-B-cell colony-enhancing factor 1 (PBEF1) or ... Revollo JR, Grimm AA, Imai S (March 2007). "The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/ ... Grolla AA, Travelli C, Genazzani AA, Sethi JK (July 2016). "Extracellular nicotinamide phosphoribosyltransferase, a new cancer ...
The first step, and the rate-limiting enzyme in the salvage pathway is nicotinamide phosphoribosyltransferase (NAMPT), which ... Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a ... Nicotinamide adenine dinucleotide has several essential roles in metabolism. It acts as a coenzyme in redox reactions, as a ... "Nicotinamide-Adenine-Dinucleotide". pubchem.ncbi.nlm.nih.gov. Nelson, David L.; Cox, Michael M. (2005). Principles of ...
... also known as alkyl adenine glycosylase (Aag). Adenine Guanine Xanthine "Estimation of Plasmodium falciparum drug ... Hypoxanthine-guanine phosphoribosyltransferase converts hypoxanthine into IMP in nucleotide salvage. Hypoxanthine is also a ... Because of its resemblance to guanine, the spontaneous deamination of adenine can lead to an error in DNA transcription/ ... including the DNA and RNA components adenine and guanine, may have been formed extraterrestrially in outer space. The Pheretima ...
In 2009, Joseph Bass in collaboration with Takahashi's group discovered that nicotinamide phosphoribosyltransferase (NAMPT) ... mediated synthesis of metabolic coenzyme nicotinamide adenine dinucleotide (NAD+), which both oscillate on a daily cycle, may ...
miR-34a suppresses the gene expression of the NAMPT gene which encodes the nicotinamide phosphoribosyltransferase (Nampt) ... enzyme which is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD) salvage pathway, resulting in reduced ...
The mechanism of action of the P7C3 series of compounds involves activation of nicotinamide phosphoribosyltransferase (NAMPT), ... the rate-limiting enzyme responsible for the transformation of nicotinamide into nicotinamide adenine dinucleotide (NAD). By ...
"Adenine phosphoribosyltransferase isoforms of Arabidopsis and their potential contributions to adenine and cytokinin metabolism ... Adenine phosphoribosyltransferase (APRTase) is an enzyme encoded by the APRT gene, found in humans on chromosome 16. It is part ... Adenine+phosphoribosyltransferase at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Human APRT genome ... Takeuchi H, Kaneko Y, Fujita J, Yoshida O (Apr 1993). "A case of a compound heterozygote for adenine phosphoribosyltransferase ...
Adenine phosphoribosyltransferase (APRT) deficiency is an inherited condition that affects the kidneys and urinary tract. ... medlineplus.gov/genetics/condition/adenine-phosphoribosyltransferase-deficiency/ Adenine phosphoribosyltransferase deficiency. ... Adenine phosphoribosyltransferase (APRT) deficiency is an inherited condition that affects the kidneys and urinary tract. The ... Adenine phosphoribosyltransferase deficiency in children. Pediatr Nephrol. 2012 Apr;27(4):571-9. doi: 10.1007/s00467-011-2037-0 ...
Protein target information for Adenine phosphoribosyltransferase (Anaeromyxobacter dehalogenans 2CP-1). Find diseases ...
ADENINE PHOSPHORIBOSYLTRANSFERASESulfate Ion
"Crystallization of the purine salvage enzyme adenine phosphoribosyltransferase",. abstract = "Adenine phosphoribosyltransferase ... Adenine phosphoribosyltransferase from the protozoan parasite Leishmania donovani has been crystallized in the presence of the ... N2 - Adenine phosphoribosyltransferase from the protozoan parasite Leishmania donovani has been crystallized in the presence of ... AB - Adenine phosphoribosyltransferase from the protozoan parasite Leishmania donovani has been crystallized in the presence of ...
Phenotype and genotype characterization of adenine phosphoribosyltransferase deficiency. J. Am. Soc. Nephrol. 21, 679-688 (2010 ... Jaffer, A., Joyce, A., Koenig, P. & Biyani, C. S. Adenine phosphoribosyltransferase deficiency: a rare cause of recurrent ... Kidney disease in adenine phosphoribosyltransferase deficiency. Am. J. Kidney Dis. 67, 431-438 (2016). ... Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase deficiencies. Hum. Genet. 75, 163-168 (1987 ...
Adenine phosphoribosyltransferase (APRT) (EC 2.4.2.7). 2.4.2.7 Homo sapiens Purine-Pyrimidine Metabolic Disorder,Urolithiasis, ... Adenine Phosphoribosyltransferase Deficiency,Charcot-Marie-Tooth Disease, X-Linked Recessive, 5,Orotic Aciduria,Postaxial ... Adenine Phosphoribosyltransferase Deficiency,Xanthinuria,Molybdenum Cofactor Deficiency, Complementation Group A, ... Uridine 5-monophosphate synthase (UMP synthase) [Includes: Orotate phosphoribosyltransferase (OPRT) (OPRTase) (EC 2.4.2.10); ...
adenine phosphoribosyltransferase APT2 Feature Type. ORF , Verified Paralog. APT1 3 EC Number. 2.4.2.7 Summary. APT2 has a ...
... adenine phosphoribosyltransferase deficiency (ortholog); autism spectrum disorder (ortholog); FOUND IN lysosome (ortholog); ... adenine phosphoribosyltransferase deficiency ISO. RGD:1343157. 8554872. ClinVar Annotator: match by term: Adenine ... phosphoribosyltransferase deficiency. ClinVar. PMID:25741868, PMID:28492532. autosomal recessive chronic granulomatous disease ...
Group 1: The patient may have deficiencies in hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine ... adenine phosphoribosyltransferase, HGPRT) should be suspected if gout develops at an early age, if a family history of early ... These include 2- or 8-dihydroxyadenine, adenine, xanthine, and uric acid. The crystals of uric acid may initiate calcium ... phosphoribosyltransferase, or xanthine dehydrogenase enzymes. Mutations for these gene products occur as autosomal recessive, ...
In the end of the KP, QUIN is degraded to nicotinamide adenine dinucleotide by quinolinic acid phosphoribosyltransferase. ... quinolinic acid phosphoribosyltransferase; TDO: tryptophan 2,3-dioxygenase; TPH: tryptophan hydroxylase. ... quinolinic acid phosphoribosyltransferase; TDO: tryptophan 2,3-dioxygenase; TPH: tryptophan hydroxylase. ...
Adenine phosphoribosyltransferase deficiency; chronic renal failure; microchimerism and organ transplantation; Alzheimers ...
In patients with a congenital adenine phosphoribosyltransferase (A-PRTase) deficiency, urolithiasis caused by the formation of ... 先天性adenine phosphoribosyltransferase欠損症における尿路結石形
In patients with a congenital adenine phosphoribosyltransferase (A-PRTase) deficiency, urolithiasis caused by the formation of ... 先天性adenine phosphoribosyltransferase欠損症における尿路結石形
We focused on Adenine Phosphoribosyltransferase (APRT) and demonstrated the detrimental consequence of APRT gene silencing on ...
The cyclic influence of core circadian proteins on nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide ( ...
Adenine phosphoribosyltransferase deficiency This is a rare autosomal recessive Autosomal Recessive Genetic disorders ... Treatment of adenine phosphoribosyltransferase deficiency is with dietary purine restriction, high fluid intake, and avoidance ... Diagnosis of adenine phosphoribosyltransferase deficiency is by detecting elevated levels of 2,8-dihyroxyadenine, 8- ... read more disorder that results in the inability to salvage adenine for purine synthesis. Accumulated adenine is oxidized to 2, ...
Adenine phosphoribosyltransferase ELISA KIT; apt ELISA KIT; IPF_3953 ELISA KIT; APRT ELISA KIT. ...
Phenotype data for mouse gene Nt5dc2. Discover Nt5dc2s significant phenotypes, expression, images, histopathology and more. Data for gene Nt5dc2 is all freely available for download.
adenine phosphoribosyltransferase [S.... ARG1. 383. ARG1. arginase 1 [Source:HGNC Symbol;Acc:H.... ...
Adenine phosphoribosyltransferase deficiency is a rare genetic disorder where an enzyme (2, 8-dihydroxyadenine) deficiency ...
Recombinant Streptococcus pyogenes serotype M1 Adenine phosphoribosyltransferase(apt). CSB-YP001954SMT. Yeast. Recombinant ...
... and adenine phosphoribosyltransferase (BEWA_017730) are present, indicating that purine salvage can occur, similar to P. ... De novo purine biosynthesis is absent, however, unlike other piroplasms, hypoxanthine/guanine phosphoribosyl transferase (BEWA_ ...
Phosphoribosyltransferase. *Adenine phosphoribosyltransferase. *Hypoxanthine-guanine phosphoribosyltransferase. *Uracil ...
Adenine is salvaged by the enzyme adenine phosphoribosyltransferase (APRT). * Guanine and hypoxanthine are salvaged by the ... In DNA, thymine complementary pairs with adenine whereas in RNA, uracil matches with adenine. The thymine differs from uracil ... Purines are adenine and guanine whereas the nitrogenous bases of pyrimidines are cytosine, thymine, and uracil. These five ... The nucleobases adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U) are referred to as primary or canonical. ...
Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency. Runolfsdottir Hrafnhildur L, et al ...
Adenine phosphoribosyltransferase. 95.51%. PM0084009. 43. A0A6M2Y7G5. HTH-type transcriptional regulator GltR. 95.55%. ...
AutoFact: adenine phosphoribosyltransferase [Brassica napus] 6.0e-06 • FL-Next: tr=Putative uncharacterized protein; Picea ... AutoFact: Adenine phosphoribosyltransferase n=1 Tax=Intrasporangium calvum DSM 43043 RepID=E6SB75_INTC7 2.0e-31 ... AutoFact: Adenine phosphoribosyltransferase n=1 Tax=Herpetosiphon aurantiacus ATCC 23779 RepID=APT_HERA2 2.0e-16 ... AutoFact: Adenine phosphoribosyltransferase 1 n=1 Tax=Elaeis guineensis RepID=B3TLV7_ELAGV 2.0e-37 ...
... adenine phosphoribosyltransferase.. Allopurinol Accord is indicated for the management of 2,8-dihydroxyadenine (2,8-DHA) renal ... adenine phosphoribosyltransferase. Allopurinol Accord is indicated for the management of 2,8-dihydroxyadenine (2,8-DHA) renal ... stones related to deficient activity of adenine phosphoribosyltransferase.. Allopurinol Accord is indicated for the management ... stones related to deficient activity of adenine phosphoribosyltransferase.. Allopurinol Accord is indicated for the management ...
  • Adenine phosphoribosyltransferase (APRT) deficiency is an inherited condition that affects the kidneys and urinary tract. (medlineplus.gov)
  • Adenine phosphoribosyltransferase (APRT) deficiency is characterized by excessive production and renal excretion of 2,8-dihydroxyadenine (DHA), which leads to kidney stone formation and crystal-induced kidney damage (i.e. (nih.gov)
  • Complete deficiency of adenine phosphoribosyltransferase: a third case presenting as renal stones in a young child. (bmj.com)
  • As a first step in understanding the function of IMPT1, we identified the renal structures expressing this gene in knockout mice with adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadenine (DHA) nephrolithiasis. (nih.gov)
  • 19. [Sideroblastic anemia associated with adenine phosphoribosyltransferase deficiency]. (nih.gov)
  • In adenosine deaminase deficiency, adenosine and adenine accumulate in the plasma. (medscape.com)
  • It is produced by individuals who suffer from adenine phosphoribosyltransferase (APRT) deficiency, a rare autosomal recessive error of purine metabolism. (mcw.edu)
  • Adenine phosphoribosyltransferase (APRTase) is an enzyme encoded by the APRT gene, found in humans on chromosome 16. (wikipedia.org)
  • APRT is functionally related to hypoxanthine-guanine phosphoribosyltransferase (HPRT). (wikipedia.org)
  • This gene provides instructions for making APRT, an enzyme that helps to convert a DNA building block (nucleotide) called adenine to a molecule called adenosine monophosphate (AMP). (medlineplus.gov)
  • Add to 10260: Adenine phosphoribosyltransferase variants By study of man-mouse hybrid clones Ruddle's group (1972) could demonstrate that the APRT locus is on chromosome No. 16. (nih.gov)
  • This study aimed at disclosing the role of ATPase α submit and the adenine phosphoribosyl transferase (APRT) in BNS male sterility. (chinacrops.org)
  • APRTase catalyzes the following reaction in the purine nucleotide salvage pathway: Adenine + Phosphoribosyl Pyrophosphate (PRPP) → Adenylate (AMP) + Pyrophosphate (PPi) In organisms that can synthesize purines de novo, the nucleotide salvage pathway provides an alternative that is energetically more efficient. (wikipedia.org)
  • Adenosine phosphoribosyl transferase(E.C:2.4.2.7), involved in the one-step salvage of adenine to AMP. (or.jp)
  • 1]Xing Q H, Ru Z G, Li J, Zhou C J, Jin D M, Sun Y, Wang B. Cloning a second form of adenine phosphoribosyl transferase gene (TaAPT2) from wheat and analysis of its association with thermo-sensitive genic male sterility (TGMS). (chinacrops.org)
  • Group 1: The patient may have deficiencies in hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase, or xanthine dehydrogenase enzymes. (medscape.com)
  • It can salvage adenine from the polyamine biosynthetic pathway or from dietary sources of purines. (wikipedia.org)
  • disorder that results in the inability to salvage adenine for purine synthesis. (msdmanuals.com)
  • It can act as a salvage enzyme for recycling of adenine into nucleic acids. (bvsalud.org)
  • An enzyme catalyzing the formation of AMP from adenine and phosphoribosylpyrophosphate. (bvsalud.org)
  • Purines include adenine and guanine whereas pyrimidines include cytosine , thymine , and uracil . (biologyonline.com)
  • Adenine can be distinguished from guanine by its amine group at position 6 and the presence of an additional double bond between N-1 and C-6 in its heterocyclic aromatic (pyrimidine) ring. (biologyonline.com)
  • Add to 10265: Adenine B auxotroph, human complement for hamster Studying hybrids between hamster cells carrying induced auxotrophic mutation and normal human cells, Kao and Puck (1972) defined a linkage between an adenine B auxotroph complementing gene and a gene necessary for expression of three esterase bands (13335). (nih.gov)
  • When APRTase has reduced or nonexistent activity, adenine accumulates from other pathways. (wikipedia.org)
  • Kidney disease progression is thought to result from a multitude of metabolic and genetic changes, including hypoxia and adenine. (asn-online.org)
  • Under these hypoxic conditions, MTAP pathway was perturbed leading to adenine accumulation in kidney organoid cells, suggesting a potential mechanism of endogenous adenine generation contributing to kidney disease. (asn-online.org)
  • It is a highly insoluble metabolite of adenine that causes radiolucent urolithiasis. (mcw.edu)
  • MALDI-MSI of hypoxic kidney organoids revealed an increased intensity of adenine metabolite and decreased intensity of TCA metabolites such as malic acid. (asn-online.org)
  • The hood, which contains the adenine binding site, has more variability within the family of enzymes. (wikipedia.org)
  • Accumulated adenine is oxidized to 2,8-dihyroxyadenine, which precipitates in the urinary tract, causing problems similar to those of uric acid nephropathy (eg, renal colic, frequent infections, and, if diagnosed late, renal failure). (msdmanuals.com)
  • Allopurinol Nycomed is indicated for the management of 2,8-dihydroxyadenine (2,8-DHA) renal stones related to deficient activity of adenine phosphoribosyltransferase. (pillintrip.com)
  • Recently, a pathway contributing to endogenous adenine production was identified (manuscript in revision). (asn-online.org)
  • The enzyme first binds PRPP, followed by adenine. (wikipedia.org)
  • A lack of functional enzyme impairs the conversion of adenine to AMP. (medlineplus.gov)
  • We explored the association between adenine, kidney hypoxia and kidney injury using a human kidney organoid system with multi-omic analysis. (asn-online.org)
  • A member of the class of 6-aminopurines that is adenine bearing two hydroxy substituents at positions 2 and 8. (mcw.edu)