Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By in vitro assay, 6 important enzymatic activities of human skin homogenates were determined following an incubation with D-penicillamine in concentrations between 10(-4) and 10 mg/ml, i.e. 67 X 10(-5) and 67 mM/l. The following enzymatic activities were recorded: lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alkaline phosphatase (AP), acid phosphatase (AcP), and "leucine aminopeptidase" (LAP). A dose-dependent activation by D-penicillamine occurred in the case of G-6-PDH- and AcP-activities, a dose-dependent inhibition by D-penicillamine was found with AP- and GAPDH-activities. LDH- and LAP-activities remained unchanged in the presence of D-penicillamine in concentrations up to 10 mg/ml (67 mM/l). From the data of pharmacokinetic studies in rats it may be concluded that concentrations of D-penicillamine which influence enzymatic activities may easily be reached in vivo, under the conditions of treating rheumatoid arthritis and Morbus Wilson. The biochemical actions of D-penicillamine are briefly discussed with secial regard to dermatological therapy and dermatological unwanted side-effects.
 ...
PMID:D-penicillamine in dermatology: influence on enzymatic activities of human skin in vitro. 120 Jul 15

Exposure of articular cartilage to H2O2 in vitro inhibits proteoglycan synthesis in a fashion which parallels the inhibition which occurs in cartilage in animal models of acute inflammation. Our study shows that exposure to H2O2 also inhibits other chondrocyte functions, including total protein and DNA synthesis. Since these intracellular biosynthetic processes require adenosine triphosphate (ATP), the effect of exposure of H2O2 on chondrocyte ATP was measured. Exposure to H2O2 caused an immediate (less than 2 min) dose dependent decrease in cartilage ATP levels--found to be due to the oxidative inactivation of glyceraldehyde-3-phosphate dehydrogenase (G-3-PDH). We suggest that intrachondrocyte oxidant damage occurs through oxidation of the sensitive thiol (-SH) residue at the active center of G-3-PDH, with subsequent reduction in the rate of glycolytic ATP synthesis and the intracellular concentration of ATP which is required for DNA, protein, proteoglycan and hyaluronic acid synthesis.
 ...
PMID:The mechanism of chondrocyte hydrogen peroxide damage. Depletion of intracellular ATP due to suppression of glycolysis caused by oxidation of glyceraldehyde-3-phosphate dehydrogenase. 271 9

A comparative immunological study of glyceraldehyde-3-phosphate dehydrogenase among Enterobacteriaceae was carried out with an antiserum against Enterobacter intermedium G-3-PDH. Results of immunodiffusion experiments and microcomplement fixation studies showed E. intermedium to be a homogeneous species. The genera Enterobacter and Escherichia were found to be quite heterogeneous.
 ...
PMID:[Comparative immunological study of glyceraldehydephosphate dehydrogenase in Enterobacteriaceae: contribution of an anti-glyceraldehydephosphate dehydrogenase antiserum of Enterobacter intermedium]. 311 6

The comparative immunological study of glyceraldehyde-3-phosphate dehydrogenase (G-3-PDH) among Enterobacteriaceae carried out with an anti-Enterobacter cloacae G-3-PDH serum pointed out the large heterogeneity of the genera Enterobacter and Escherichia. The use of two-dimensional maps integrating our new data and previously acquired quantitative data confirmed these results.
 ...
PMID:Immunological relationship among glyceraldehyde-3-phosphate dehydrogenases in the genera Enterobacter and Escherichia. 317 57

Cathepsins M and B from rabbit liver lysosomes were separated by chromatography on Ultrogel AcA34 at low ionic strength and purified to homogeneity, and their catalytic and molecular properties were compared. Cathepsin M was relatively inactive with synthetic peptide substrates. Thus, it hydrolyzed benzoyl arginine naphthylamide at only one-fifth the rate observed with cathepsin B, and no activity was detected with Gly-Phe naphthylamide which is a relatively good substrate for cathepsin B. On the other hand, cathepsin M exhibited a preference for protein substrates. It was more active than cathepsin B in catalyzing the inactivation of the following enzymes: rabbit muscle or liver fructose-1,6-bisphosphate aldolases, rabbit liver fructose-1,6-bisphosphatase and pyruvate kinase, yeast glucose-6-phosphate dehydrogenase, and rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. With glucagon as substrate, both enzymes showed similar peptidyl dipeptidase activities with some minor differences in peptide bond specificity. Cathepsins M and B are similar in size, with apparent molecular weights of 30,200 for cathepsin M and 28,800 for cathepsin B, and in amino acid composition and carbohydrate content. Each contains approximately 2-3 equivalents/mol glucosamine, 3 equivalents/mol mannose, and no fucose or galactosamine. They also show similar microheterogeneity in sodium dodecylsulfate-gel electrophoresis and isoelectric focusing; this microheterogeneity is probably related to differences in glycosylation. Extensive homology in primary structure for the two proteins was indicated by the similar patterns of peptides formed on digestion with trypsin.
 ...
PMID:Purification and properties of rabbit liver cathepsin M and cathepsin B. 406 7

Despite use as constitutive protein standards to quantify mRNA, data are limited regarding alteration of cyclophilin or glyceraldehyde-3-phosphate dehydrogenase (G3PDH) in hypertension or angiotensin converting enzyme (ACE) inhibitor treatment. We assessed these standards in 6 month old Wistar-Kyoto rats (WKY, n = 16), compared to age-matched spontaneously hypertensive rats (SHR, n = 14). Additional SHR (n = 8) had received enalapril for 3 to 4 months at evaluation. Left ventricular (LV) and kidney RNA was extracted for dot blot cyclophilin and G3PDH cDNA hybridization. Cyclophilin and G3PDH mRNA densitometries were expressed as a ratio. Cyclophilin/G3PDH for the WKY, untreated SHR, and enalapril SHR were 1.56 +/- 0.33, 1.45 +/- 0.42, and 1.49 +/- 0.51, respectively, for the LV, and 1.52 +/- 0.09, 1.43 +/- 0.22, and 1.38 +/- 0.22, respectively, for the kidney. Differences were not significant. Relative expression of cyclophilin/G3PDH was unaffected by genetic SHR hypertension, or long term enalapril. Thus, either constitutive mRNA may be confidently used to index structural or functional protein responses, at the transcriptional level, in the SHR.
 ...
PMID:Influence of pressure overload and ACE inhibitor therapy on constitutive protein mRNA expression in the spontaneously hypertensive rat. 872 42

Notwithstanding the numerous drugs available for liver cancer, emerging evidence suggests that chemotherapeutic resistance is a significant issue. HGF and its receptor MET play critical roles in liver carcinogenesis and metastasis, mainly dependent on the activity of receptor tyrosine kinase. However, for unknown reasons, all HGF-MET kinase activity-targeted drugs have failed or have been suspended in clinical trials thus far. Macroautophagy/autophagy is a protective 'self-eating' process for resisting metabolic stress by recycling obsolete components, whereas the impact of autophagy-mediated reprogrammed metabolism on therapeutic resistance is largely unclear, especially in liver cancer. In the present study, we first observed that HGF stimulus facilitated the Warburg effect and glutaminolysis to promote biogenesis in multiple liver cancer cells. We then identified the pyruvate dehydrogenase complex (PDHC) and GLS/GLS1 as crucial substrates of HGF-activated MET kinase; MET-mediated phosphorylation inhibits PDHC activity but activates GLS to promote cancer cell metabolism and biogenesis. We further found that the key residues of kinase activity in MET (Y1234/1235) also constitute a conserved LC3-interacting region motif (Y1234-Y1235-x-V1237). Therefore, on inhibiting HGF-mediated MET kinase activation, Y1234/1235-dephosphorylated MET induced autophagy to maintain biogenesis for cancer cell survival. Moreover, we verified that Y1234/1235-dephosphorylated MET correlated with autophagy in clinical liver cancer. Finally, a combination of MET inhibitor and autophagy suppressor significantly improved the therapeutic efficiency of liver cancer in vitro and in mice. Together, our findings reveal an HGF-MET axis-coordinated functional interaction between tyrosine kinase signaling and autophagy, and establish a MET-autophagy double-targeted strategy to overcome chemotherapeutic resistance in liver cancer. Abbreviations: ALDO: aldolase, fructose-bisphosphate; CQ: chloroquine; DLAT/PDCE2: dihydrolipoamide S-acetyltransferase; EMT: epithelial-mesenchymal transition; ENO: enolase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GLS/GLS1: glutaminase; GLUL/GS: glutamine-ammonia ligase; GPI/PGI: glucose-6-phosphate isomerase; HCC: hepatocellular carcinoma; HGF: hepatocyte growth factor; HK: hexokinase; LDH: lactate dehydrogenase; LIHC: liver hepatocellular carcinoma; LIR: LC3-interacting region; PDH: pyruvate dehydrogenase; PDHA1: pyruvate dehydrogenase E1 alpha 1 subunit; PDHX: pyruvate dehydrogenase complex component X; PFK: phosphofructokinase; PK: pyruvate kinase; RTK: receptor tyrosine kinase; TCGA: The Cancer Genome Atlas.
 ...
PMID:The HGF-MET axis coordinates liver cancer metabolism and autophagy for chemotherapeutic resistance. 3078 11