Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.41 (isocitrate dehydrogenase)
 3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative effectiveness of succinate and isocitrate in supplying NADPH for cholesterol and deoxycorticosterone (DOC) metabolism by rat adrenal mitochondria has been investigated. As previously seen for cholesterol metabolism, isocitrate supported DOC metabolism at a higher rate than succinate. Maximal rates of DOC metabolism, however, required 10 times more precursor (10mM) than cholesterol metabolism. Addition of DOC to mitochondria inhibited cholesterol metabolism, indicating competition for NADPH between these pathways. Coaddition of these reducing precursors resulted in a substantially greater than additive rate of DOC hydroxylation, but not cholesterol metabolism. The synergistic effect was seen with both 11 beta- and 18 hydroxylation. For both precursors, the synergism was maximal upon addition of only 1 mM of the second precursor. The synergistic effect was far more resistant to added KCN and malonate than succinate supported DOC metabolism, and neither inhibitor affected isocitrate supported DOC metabolism. These results suggest that while cytochromes P450scc and P450(11 beta) use a common supply of NADPH generated by each precursor, there is a pool of NADPH that is only effectively synthesised upon coaddition of precursors and only utilised by cytochrome P450(11 beta). This second NADPH pool may be produced in response to potentiated isocitrate dehydrogenase activity or activation of a different NADPH generating system.
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PMID:Succinate stimulation of isocitrate supported deoxycorticosterone metabolism in rat adrenal mitochondria by a synergistic mechanism. 187 76

The objective of this study was to evaluate the effects of dietary heated fats from a commercial deep-fat frying operation on rat liver enzyme activity. The fats, partially hydrogenated soybean oil (PHSBO) used for four days and for 7 days (7-DH) for frying foodstuffs in a commercial restaurant, were fed to rats in either free access to food or by pair-feeding graded doses. All diets were isocaloric and contained 15 g/100 g of diet. Experiments were conducted with control rats fed non-heated (NH) PHSBO diet. Animals fed 7-DH diet in each set of experiments had larger amounts of cytochromes P450 and b5 and greater activity of NADPH-cytochrome P450 reductase when compared to controls. The activities of carnitine palmitoyltransferase-I and isocitrate dehydrogenase were significantly lower in rats fed test diets in comparison to controls. A significantly depressed activity of glucose 6-phosphate dehydrogenase was also noticed for these animals when compared to those fed NH. In addition, liver and microsomal protein concentrations were significantly greater in rats fed the used oils in comparison to controls, and liver glycogen was significantly lower.
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PMID:Effects of dietary heated fats on rat liver enzyme activity. 888 75

This study was conducted to investigate the effects of dietary cyclic fatty acid monomers (CFAM), contained in heated fat from a commercial deep-fat frying operation, on rat liver enzyme activity. A partially hydrogenated soybean oil (PHSBO) used 7 d (7-DH) for frying foodstuffs, or 0.15% methylated CFAM diets was fed to male weanling rats in comparison to a control group fed a nonheated PHSBO (NH) diet in a 10-wk experiment. All diets were isocaloric with 15% fat. Animals fed either CFAM or 7-DH diets showed increased hepatic content of cytochrome (cyt.) b5 and P450 and increased activity of (E.C. 1.6.2.4) NADPH-cyt. P450 reductase in comparison to the control rats. In addition, the activities of (E.C. 2.3.1.21) carnitine palmitoyltransferase-I and (E.C. 1.1.1.42) isocitrate dehydrogenase were significantly decreased when compared to that of rats fed the NH diet. A significantly depressed activity of (E.C. 1.1.1.49) glucose 6-phosphate dehydrogenase was also observed for these animals compared to the control rats fed NH diet. Moreover, liver and microsomal proteins were significantly increased when CFAM or 7-DH diets were fed to animals in comparison to controls while liver glycogen was decreased significantly in experimental groups of rats. The results obtained in this study indicate that the CFAM in the diet from either synthetic sources or used fats increase the activity of liver enzyme systems that detoxify them.
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PMID:Cyclic fatty acid monomers from dietary heated fats affect rat liver enzyme activity. 968 70

Cytochrome P450 BM-3 from Bacillus megaterium catalyzes the subterminal hydroxylation of medium- and longchain fatty acids at the omega-1, omega-2, and omega-3 positions. A continuous spectrophotometric assay for P450 BM-3 based on the conversion of p-nitrophenoxycarboxylic acids (pNCA) to omega-oxycarboxylic acids and the chromophore p-nitrophenolate was reported recently. However, this pNCA assay procedure contained steps that limited its application in high throughput screening, including expression of P450 BM-3 variant F87A in 4-ml cultures, centrifugation, resuspension of the cell pellet, and cell lysis. We have shown that permeabilization of the outer membrane of Escherichia coli DH5alpha with polymyxin B sulfate, EDTA, polyethylenimine, or sodium hexametaphosphate results in rapid conversion of 12-pNCA. A NADPH-generating system consisting of NADP(+), D/L-isocitric acid, and the D/L-isocitrate dehydrogenase of E. coli DH5alpha reduced the cofactor expense more than 10-fold. By avoiding cell lysis, resuspension, and centrifugation, the high throughput protocol allows screening of thousands of samples per day.
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PMID:Cost-effective whole-cell assay for laboratory evolution of hydroxylases in Escherichia coli. 1168 5