gamma-Glutamyltransferase: An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.Glycylglycine: The simplest of all peptides. It functions as a gamma-glutamyl acceptor.Alanine Transaminase: An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 184.108.40.206.Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 220.127.116.11.Aspartate Aminotransferases: Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 18.104.22.168.Clinical Enzyme Tests: Analyses for a specific enzyme activity, or of the level of a specific enzyme that is used to assess health and disease risk, for early detection of disease or disease prediction, diagnosis, and change in disease status.Diazooxonorleucine: An amino acid that inhibits phosphate-activated glutaminase and interferes with glutamine metabolism. It is an antineoplastic antibiotic produced by an unidentified species of Streptomyces from Peruvian soil. (From Merck Index, 11th ed)Borates: Inorganic or organic salts and esters of boric acid.Liver Function Tests: Blood tests that are used to evaluate how well a patient's liver is working and also to help diagnose liver conditions.Electrophoresis, Cellulose Acetate: Electrophoresis in which cellulose acetate is the diffusion medium.Antigens, CD13: Zinc-binding metalloproteases that are members of the type II integral membrane metalloproteases. They are expressed by GRANULOCYTES; MONOCYTES; and their precursors as well as by various non-hematopoietic cells. They release an N-terminal amino acid from a peptide, amide or arylamide.Liver Diseases: Pathological processes of the LIVER.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Glutathione: A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.Alcohol Drinking: Behaviors associated with the ingesting of alcoholic beverages, including social drinking.Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.Erythrocyte Indices: ERYTHROCYTE size and HEMOGLOBIN content or concentration, usually derived from ERYTHROCYTE COUNT; BLOOD hemoglobin concentration; and HEMATOCRIT. The indices include the mean corpuscular volume (MCV), the mean corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC).MaleatesGlucaric Acid: A sugar acid derived from D-glucose in which both the aldehydic carbon atom and the carbon atom bearing the primary hydroxyl group are oxidized to carboxylic acid groups.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.2-Acetylaminofluorene: A hepatic carcinogen whose mechanism of activation involves N-hydroxylation to the aryl hydroxamic acid followed by enzymatic sulfonation to sulfoxyfluorenylacetamide. It is used to study the carcinogenicity and mutagenicity of aromatic amines.Alcoholism: A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)Transferrin: An iron-binding beta1-globulin that is synthesized in the LIVER and secreted into the blood. It plays a central role in the transport of IRON throughout the circulation. A variety of transferrin isoforms exist in humans, including some that are considered markers for specific disease states.Aminopeptidases: A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11.Leucyl Aminopeptidase: A zinc containing enzyme of the hydrolase class that catalyzes the removal of the N-terminal amino acid from most L-peptides, particularly those with N-terminal leucine residues but not those with N-terminal lysine or arginine residues. This occurs in tissue cell cytosol, with high activity in the duodenum, liver, and kidney. The activity of this enzyme is commonly assayed using a leucine arylamide chromogenic substrate such as leucyl beta-naphthylamide.Methionine SulfoximineFreeze Drying: Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products.Bilirubin: A bile pigment that is a degradation product of HEME.Cholestasis, Extrahepatic: Impairment of bile flow in the large BILE DUCTS by mechanical obstruction or stricture due to benign or malignant processes.No-Reflow Phenomenon: Markedly reduced or absent REPERFUSION in an infarct zone following the removal of an obstruction or constriction of an artery.Enzymes: Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.Cholestasis: Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).Coffee: A beverage made from ground COFFEA beans (SEEDS) infused in hot water. It generally contains CAFFEINE and THEOPHYLLINE unless it is decaffeinated.Acetylglucosaminidase: A beta-N-Acetylhexosaminidase that catalyzes the hydrolysis of terminal, non-reducing 2-acetamido-2-deoxy-beta-glucose residues in chitobiose and higher analogs as well as in glycoproteins. Has been used widely in structural studies on bacterial cell walls and in the study of diseases such as MUCOLIPIDOSIS and various inflammatory disorders of muscle and connective tissue.L-Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.Kinetics: The rate dynamics in chemical or physical systems.Glutamate-Ammonia Ligase: An enzyme that catalyzes the conversion of ATP, L-glutamate, and NH3 to ADP, orthophosphate, and L-glutamine. It also acts more slowly on 4-methylene-L-glutamate. (From Enzyme Nomenclature, 1992) EC 22.214.171.124.Dipeptides: Peptides composed of two amino acid units.Chemistry, Clinical: The specialty of ANALYTIC CHEMISTRY applied to assays of physiologically important substances found in blood, urine, tissues, and other biological fluids for the purpose of aiding the physician in making a diagnosis or following therapy.Glutamate Dehydrogenase: An enzyme that catalyzes the conversion of L-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. (From Enzyme Nomenclature, 1992) EC 126.96.36.199.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Transglutaminases: Transglutaminases catalyze cross-linking of proteins at a GLUTAMINE in one chain with LYSINE in another chain. They include keratinocyte transglutaminase (TGM1 or TGK), tissue transglutaminase (TGM2 or TGC), plasma transglutaminase involved with coagulation (FACTOR XIII and FACTOR XIIIa), hair follicle transglutaminase, and prostate transglutaminase. Although structures differ, they share an active site (YGQCW) and strict CALCIUM dependence.Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Liver Neoplasms: Tumors or cancer of the LIVER.Microvilli: Minute projections of cell membranes which greatly increase the surface area of the cell.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Liver function tests: LFT}}GlycylglycineAlanine transaminase: Alanine transaminase (ALT) is a transaminase enzyme (). It is also called alanine aminotransferase (ALAT) and was formerly called serum glutamate-pyruvate transaminase (SGPT) or serum glutamic-pyruvic transaminase (SGPT).Elevated alkaline phosphataseTransaminaseBorate: Borates are the name for a large number of boron-containing oxyanions. The term "borates" may also refer to tetrahedral boron anions, or more loosely to chemical compounds which contain borate anions of either description.Liver biopsyAlanine aminopeptidase: Alanine aminopeptidase () is an enzyme that is used as a biomarker to detect damage to the kidneys, and that may be used to help diagnose certain kidney disorders. It is found at high levels in the urine when there are kidney problems.American Association for the Study of Liver Diseases: The American Association for the Study of Liver Diseases (AASLD) is the leading organization of scientists and health care professionals committed to preventing and curing liver disease. AASLD was founded in 1950 by a small group of leading liver specialists (including Hans Popper, Leon Schiff, Fred Hoffbauer, Cecil Watson, Jesse Bollman, and Sheila Sherlock, to name a few) to bring together those who had contributed to the field of hepatology.Liver sinusoid: A liver sinusoid is a type of sinusoidal blood vessel (with fenestrated, discontinuous endothelium) that serves as a location for the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.SIU SOM Histology GIAlcohol and cardiovascular disease: Excessive alcohol intake is associated with an elevated risk of alcoholic liver disease (ALD), heart failure, some cancers, and accidental injury, and is a leading cause of preventable death in industrialized countries. However, extensive research has shown that moderate alcohol intake is associated with health benefits, including less cardiovascular disease, diabetes, hypertension, and lower all-cause mortality.IsoxazoleRed blood cell distribution width: right|frame|Human red blood cellsDese Dem Dose: Dese Dem Dose is a 1935 instrumental composed by Glenn Miller and recorded by The Dorsey Brothers orchestra.Iron sucroseBiomarkers of aging: Biomarkers of aging are biomarkers that better predict functional capacity at a later age than chronological age. Stated another way, biomarkers of aging would give the true "biological age", which may be different from the chronological age.Research Society on Alcoholism: The Research Society on Alcoholism (RSA) is a learned society of over 1600 active members based in Austin, Texas. Its objective is to advance research on alcoholism and the physiological and cognitive effects of alcohol.Carbohydrate deficient transferrinUbenimexLeucyl aminopeptidase: Leucyl aminopeptidases (, leucine aminopeptidase, LAPs, leucyl peptidase, peptidase S, cytosol aminopeptidase, cathepsin III, L-leucine aminopeptidase, leucinaminopeptidase, leucinamide aminopeptidase, FTBL proteins, proteinates FTBL, aminopeptidase II, aminopeptidase III, aminopeptidase I) are enzymes that preferentially catalyze the hydrolysis of leucine residues at the N-terminus of peptides and proteins. Other N-terminal residues can also be cleaved, however.BilirubinEnzyme Commission number: The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze.White coffee: White coffee can refer to any of a number of different kinds of coffees or coffee substitutes worldwide.Lactate dehydrogenase elevating virus: Lactate dehydrogenase elevating virus, or LDV for short, belongs to part of the arteriviridae family and the nidovirales order. Also included in the nidovirales order are the coronaviridae.Burst kinetics: Burst kinetics is a form of enzyme kinetics that refers to an initial high velocity of enzymatic turnover when adding enzyme to substrate. This initial period of high velocity product formation is referred to as the "Burst Phase".Glutamine synthetaseDipeptide: A dipeptide is a sometimes ambiguous designation of two classes of organic compounds: Its molecules contain either two amino acids joined by a single peptide bond or one amino acid with two peptide bonds.Clinical Biochemistry: Clinical Biochemistry is a peer-reviewed scientific journal covering the analytical and clinical investigation of laboratory tests in humans used for diagnosis, molecular biology and genetics, prognosis, treatment and therapy, and monitoring of disease ; the discipline of clinical biochemistry. It is the official journal of the Canadian Society of Clinical Chemists.Glutamate dehydrogenase: Glutamate dehydrogenase (GLDH) is an enzyme, present in most microbes and the mitochondria of eukaryotes, as are some of the other enzymes required for urea synthesis, that converts glutamate to α-ketoglutarate, and vice versa. In animals, the produced ammonia is usually used as a substrate in the urea cycle.Benzopyrone: Benzopyrone may refer to either of two ketone derivatives of benzopyran which constitute the core skeleton of many flavonoid compounds:Transglutaminase: A transglutaminase is an enzyme that catalyzes the formation of an isopeptide bond between a free amine group (e.g.Isozyme: Isozymes (also known as isoenzymes or more generally as Multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. These enzymes usually display different kinetic parameters (e.Metastatic liver disease: A liver metastasis is a malignant tumor in the liver that has spread from another organ affected by cancer. The liver is a common site for metastatic disease because of its rich, dual blood supply (the liver receives blood via the hepatic artery and portal vein).MicrovillusKidney: The kidneys are bean-shaped organs that serve several essential regulatory roles in vertebrates. They remove excess organic molecules from the blood, and it is by this action that their best-known function is performed: the removal of waste products of metabolism.
(1/1552) Involvement of polyomavirus enhancer activator 3 in the regulation of expression of gamma-glutamyl transpeptidase messenger ribonucleic acid-IV in the rat epididymis.
Gamma-glutamyl transpeptidase (GGT) mRNA-IV and polyomavirus enhancer activator 3 (PEA3) mRNA are highly expressed in the initial segment of the rat epididymis, and both are regulated by testicular factors. PEA3 protein in rat initial segment nuclear extracts has been shown to bind to a PEA3/Ets binding motif, which is derived from the partially characterized GGT mRNA-IV promoter region. This suggests that PEA3 may be involved in regulating transcription from the rat GGT mRNA-IV gene promoter in the initial segment. Using DNA oligonucleotide primers and DNA sequencing analysis, an approximately 1500-basepair (bp) DNA sequence at the 5' region of the promoter was obtained. Using transient transfection, PEA3 activated transcription of the rat GGT mRNA-IV promoter only in cultured epididymal cells from the rat initial segment, but not in Cos-1 or NRK-52E cells. Promoter deletion analysis indicated that a PEA3/Ets binding motif between nucleotides -22 and -17 is the functional site for PEA3 to activate transcription of GGT promoter IV and that an adjacent Sp1 binding motif is also required to maintain promoter IV activity in epididymal cells. Transcriptional activation of promoter IV was shown to be epididymal cell-specific and PEA3-specific. In addition, PEA3 may act as a weak repressor for transcription of promoter IV, probably using a PEA3/Ets binding motif(s) distal to the transcription start site. A model of how PEA3 is involved in the regulation of transcription of GGT promoter IV in epididymal cells is proposed. (+info)
(2/1552) Immunohistochemical localization of 5-oxo-L-prolinase, an enzyme of the gamma-glutamyl cycle, in porcine brain microvessels.
The immunohistochemical analysis of the distribution of 5-oxo-L-prolinase in porcine brain at the light microscopic level was performed with an antibody raised against the enzyme purified from pig kidney. The present study reveals the specific expression of 5-oxo-L-prolinase in brain capillaries with an average diameter of 4.1+/-0.9 microm, while larger blood vessels remain unstained. Porcine kidney and skeletal muscle show no endothelial-specific staining with the antibody. In some cases, the asymmetrical staining pattern in cross and longitudinal sections of brain microvessels indicate endothelial- but also pericyte-specific expression. (+info)
(3/1552) Inhibition of the hydrolytic and transpeptidase activities of rat kidney gamma-glutamyl transpeptidase by specific monoclonal antibodies.
Monoclonal antibodies (mAb) against the native form of rat kidney gamma-glutamyl transpeptidase (GGT) were isolated by screening hybridomas with rat kidney brush-border membrane vesicles. They were directed against protein rather than sugar epitopes in that each recognized all GGT isoforms. All of them inhibited partially the enzyme activity of GGT. They were specific in that they inhibited the rat enzyme, but not the mouse or human enzyme. Kinetic analyses were carried out with free GGT and GGT-mAb complexes with d-gamma-glutamyl-p-nitroanilide in the presence or absence of maleate, or in the presence or absence of alanine, cysteine, cystine or glycylglycine as gamma-glutamyl acceptors. mAbs 2A10 and 2E9 inhibited the hydrolytic and glutaminase activities of GGT and had little effect on the transpeptidation activity of the enzyme, whereas mAbs 4D7 and 5F10 inhibited transpeptidation, but not hydrolytic or glutaminase activities. mAb 5F10 mimicked the effect of maleate on GGT, in that it inhibited transpeptidation, enhanced the glutaminase activity and increased the affinity of the donor site of GGT for acivicin. Such mAbs may be useful for long-term studies in tissue cultures and in vivo, and for the identification of GGT epitopes that are important for the hydrolytic and transpeptidase activities. (+info)
(4/1552) Fatty liver--an additional and treatable feature of the insulin resistance syndrome.
To test the hypothesis that fatty liver coexists with other metabolic abnormalities of the insulin resistance syndrome, and responds to their amelioration, we prospectively studied 48 consecutive patients with chronically elevated liver enzymes and clinical, ultrasound and histological findings consistent with fatty infiltration of the liver. Most of the patients were overweight or obese (64%) with increased waist circumference which closely relates to visceral fat. Only 10% of the patients had normal glucose tolerance: 44% had diabetes mellitus, 29% impaired glucose tolerance, and 17% were hyperinsulinaemic. The most common dyslipidaemia found was hypertriglyceridaemia and/or low HDL-C (86%). Dietary intervention and follow-up (median 24 months), supplemented by oral hypoglycaemic or lipid-lowering drugs as needed, resulted not only in weight loss (mean 3.7 kg), decreased fasting blood glucose (p < 0.005) and improvement in serum lipid profile (p < 0.02 for both triglycerides or HDL-C) but also in an improvement of serum liver enzymes in 96%, which became normal in more than half of the patients. Thus, fatty liver was strongly associated with many features of the insulin resistance syndrome, and follow-up revealed a high potential for reversibility and a benign course. (+info)
(5/1552) Metabolism of aminoacyl-p-nitroanilides by rat mammary tissue.
We have examined the metabolism of aminoacyl-p-nitroanilides by rat mammary tissue isolated from rats during late pregnancy, peak lactation and late lactation. The rate of hydrolysis depended upon the chemical nature of the aminoacyl-p-nitroanilide compound and the physiological state of the donor animals. Thus, mammary tissue isolated from rats during late pregnancy and peak lactation hydrolysed aminoacyl-p-nitroanilides in the order L-met-p-nitroanilide=L-leu-p-nitroanilide>L-lys-p-nitroanilide>gamma- glu-p-nitroanilide. The order of activity was the same for mammary tissue taken from rats during late lactation except that L-lys-p-nitroanilide was hydrolysed at the same rate as the neutral aminoacyl-p-nitroanilides. Mammary tissue from peak lactating rats also hydrolysed alpha-L-glu-p-nitroanilide and alpha-L-asp-p-nitroanilide but to a lesser extent than the other compounds tested. The anionic aminoacyl-p-nitroanilides were able to trans-stimulate D-aspartate efflux from mammary tissue explants and the perfused mammary gland via the high-affinity anionic amino acid carrier. The clearance of gly-L-phe by the perfused mammary gland was markedly inhibited by L-phe. The results suggest that mammary tissue expresses a variety of dipeptidases at the basolateral aspect of the mammary epithelium which are capable of hydrolysing peptides extracellularly. These enzymes may be important for providing amino acids for milk protein synthesis and/or inactivating signal peptides. (+info)
(6/1552) The induction of GSH synthesis by nanomolar concentrations of NO in endothelial cells: a role for gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase.
Nitric oxide protects cells from oxidative stress through a number of direct scavenging reactions with free radicals but the effects of nitric oxide on the regulation of antioxidant enzymes are only now emerging. Using bovine aortic endothelial cells as a model, we show that nitric oxide, at physiological rates of production (1-3 nM/s), is capable of inducing the synthesis of glutathione through a mechanism involving gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase. This novel nitric oxide signalling pathway is cGMP-independent and we hypothesize that it makes an important contribution to the anti-atherosclerotic and antioxidant properties of nitric oxide. (+info)
(7/1552) Gamma-glutamyl transpeptidase accelerates tumor growth and increases the resistance of tumors to cisplatin in vivo.
We have shown previously that gamma-glutamyl transpeptidase (GGT) activity is essential for the nephrotoxicity of cisplatin. In this study we asked whether GGT activity was necessary for the antitumor activity of cisplatin. GGT was transfected into PC3 cells, a human prostate tumor cell line. Two independent GGT-positive cell lines were isolated and characterized. GGT cleaves extracellular glutathione providing the cells with access to additional cysteine. Expression of GGT had no effect on the growth rate of the cells in vitro where the culture medium contains high levels of cysteine. However, when the cells were injected into nude mice the GGT-positive tumors grew at more than twice the rate of the GGT-negative tumors. Weekly treatment with cisplatin was toxic to both GGT-positive and -negative tumors. The GGT-positive tumors were significantly more resistant to the toxicity of cisplatin than the GGT-negative tumors. Therefore, expression of GGT is required for the nephrotoxicity of cisplatin, but diminishes the tumor toxicity of the drug. These results indicate that the nephrotoxicity and the tumor toxicity of cisplatin are via two distinct pathways. (+info)
(8/1552) Nordihydroguairetic acid is a potent inhibitor of ferric-nitrilotriacetate-mediated hepatic and renal toxicity, and renal tumour promotion, in mice.
Ferric-nitrilotriacetate (Fe-NTA) is a known renal carcinogen. In the present study, we report the effect of a potent lignin-derived herbal antioxidant, nordihydroguairetic acid (NDGA), against Fe-NTA-mediated tissue toxicity. Fe-NTA (alone) treatment of mice enhances ornithine decarboxylase activity to 259% in liver and 341% in kidney and increases [3H]thymidine incorporation in DNA to 250% in liver and 324% in kidney compared with the corresponding saline-treated controls. The enhanced ornithine decarboxylase activity and DNA synthesis showed a reduction to 138 and 123%, respectively, in liver at a higher dose of 2 mg NDGA/day/animal whereas in kidney the reduction was to 118 and 102%, respectively, compared with the corresponding saline-treated controls. In the Fe-NTA (alone)-treated group, a 12% renal tumour incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated and Fe-NTA-promoted animals, the percentage tumour incidence was increased to 68% as compared with untreated controls. No tumour incidence was recorded in the DEN-initiated, non-promoted group. The administration of NDGA, afforded >80% protection against DEN- and Fe-NTA-mediated renal tissue injury in vivo. Fe-NTA treatment also enhanced hepatic and renal microsomal lipid peroxidation to 170 and 205% of saline-treated controls, respectively, and hydrogen peroxide generation by >2.5-fold in both tissues accompanied by a 51 and 21% decrease in the level of glutathione and 35-48 and 35-50% decrease in the activities of glutathione-metabolizing and antioxidant enzymes in liver and kidney, respectively. These changes were reversed significantly in animals receiving a pre-treatment of NDGA. Our data show that NDGA can abrogate the toxic and tumour-promoting effects of Fe-NTA in liver and kidney of mice and can serve as a potent chemopreventive agent to suppress oxidant-induced tissue injury and tumorigenesis. (+info)