Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Effects of androgens, prolactin (Prl) and bromocriptine (Br) on the specific activities of prostatic (caudal and cranial) enzymes of the pyruvate-malate cycle were studied in castrated mature bonnet monkeys. Castration decreased the activity of NADP+ isocitrate dehydrogenase (ICDH), ATP citrate lyase, malate dehydrogenase (MDH), malic enzyme and fatty acid synthase (FAS). Administration of testosterone propionate (TP)/dihydrotestosterone (DHT) increased the activities of all these enzymes in both lobes. Malate dehydrogenase maintained normal activity. Prl also had a stimulatory effect on the enzymes and was further enhanced when Prl was given in combination with TP/DHT. Unlike Prl, bromocriptine treatment inhibited all the enzymes in both lobes. Thus, prolactin was found to have a direct as well as a synergistic effect with androgens on enzymes of the pyruvate-malate cycle in the prostate of castrated mature monkeys.
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PMID:Interaction of androgens and prolactin on prostatic enzymes of the pyruvate-malate cycle involved in lipogenesis in castrated mature monkey, Macaca radiata. 151 27

Addition of triiodothyronine (T3) to chick-embryo hepatocytes in culture causes increased accumulations of malic enzyme, fatty acid synthase, acetyl-CoA carboxylase and their mRNAs. H-8 and other protein kinase inhibitors inhibited the T3-induced accumulations of these lipogenic enzymes and their mRNAs but had no effect on the activities of 6-phosphogluconate dehydrogenase and isocitrate dehydrogenase, enzymes not induced by T3 in chick-embryo hepatocytes. H-8 also had no effect on the activities of malic enzyme, fatty acid synthase, and acetyl-CoA carboxylase in hepatocytes not treated with T3. Synthesis of soluble protein, levels of mRNAs for beta-actin and glyceraldehyde-3-phosphate dehydrogenase, and induction of metallothionein mRNA by Zn2+ were unaffected by H-8 at concentrations that inhibited the T3-induced accumulation of lipogenic enzymes and their mRNAs. H-8 inhibited T3-induced transcription of the genes for both malic enzyme and fatty acid synthase but had little effect on transcription of the beta-actin or glyceraldehyde-3-phosphate dehydrogenase genes or on total RNA synthesis in isolated nuclei. H-8 also had no effect on binding of T3 to its nuclear receptor. In isolated nuclei, H-8 inhibited phosphorylation of total protein by 15-20%. Phosphorylation of only one major protein was consistently and substantially inhibited, indicating that the effect of H-8 was selective. These results suggest that on-going protein phosphorylation is required specifically for stimulation of transcription of the lipogenic genes by T3.
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PMID:Triiodothyronine-induced accumulations of malic enzyme, fatty acid synthase, acetyl-coenzyme A carboxylase, and their mRNAs are blocked by protein kinase inhibitors. Transcription is the affected step. 168 Jan 29

The interaction of androgens and prolactin, the major factors regulating the male accessory sex organs, on the specific activity of seminal vesicular enzymes of the pyruvate/malate cycle were studied in castrated mature monkeys. Castration decreased the activity of these enzymes, including NADP+ isocitrate dehydrogenase, ATP citrate lyase, malate dehydrogenase, malic enzyme and fatty acid synthase. Testosterone propionate (TP)/dihydrotestosterone given as replacement to castrates increased the activity of all these enzymes, except for malate dehydrogenase. Prolactin restored normal activity of ATP citrate lyase, malic enzyme and fatty acid synthase but not of isocitrate dehydrogenase and malate dehydrogenase (MDH). Prolactin had a specific control over MDH. Moreover, when prolactin was combined with androgens a further stimulatory influence was observed on fatty acid synthase activity. In order to prove the direct influence of prolactin on enzymes of the pyruvate/malate cycle, bromocriptine was administered and this inhibited all of the enzymes. Thus prolactin was found to have a direct, as well as a synergistic, action with androgens on enzymes of the pyruvate/malate cycle in the seminal vesicles of monkeys.
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PMID:Effects of androgens, prolactin and bromocriptine on seminal vesicular enzymes of the pyruvate malate cycle involved in lipogenesis in castrated mature monkeys, Macaca radiata. 337 45

Chicks were given biotin-deficient diets containing either suboptimal (low) or supraoptimal (high) concentrations of protein from 1-d-old until they were used during their fourth week of life. The low-protein diet predisposed chicks to develop fatty liver and kidney syndrome and the high-protein diet to develop classical biotin deficiency signs. Two other groups, as controls, received biotin-supplemented rations. Low dietary protein increased lipogenesis by isolated hepatocytes but had little effect on gluconeogenesis compared to high dietary protein. Low dietary protein decreased activities of hepatic isocitrate dehydrogenase (EC 1.1.1.42), fructose-1,6-bisphosphatase (EC 3.1.3.11) and glucose-6-phosphatase (EC 3.1.3.9; GP) and increased activities of fatty acid synthase (FAS), citrate cleavage enzyme (EC 4.1.3.8; CCE) and malate dehydrogenase (decarboxylating) (EC 1.1.1.39). When biotin deficiency was superimposed, the rate of lipogenesis by isolated hepatocytes (from fed birds) was decreased. Gluconeogenesis from lactate and glycerol was also depressed. Activity of GP was further decreased by biotin deficiency on the low-protein regimen and FAS and CCE were further increased. PK activity was increased by biotin deficiency.
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PMID:The effect of biotin deficiency and dietary protein content on lipogenesis, gluconeogenesis and related enzyme activities in chick liver. 661 62

The hypothesis is advanced that NADP(+)-malic enzyme (ME; EC 1.1.1.40) is an important activity in regulating the extent of lipid accumulation in filamentous fungi. In Mucor circinelloides, a fungus capable of accumulating only 25% (w/w, dry wt) lipid, even under the most propitious conditions, ME disappears 15-20 h after nitrogen exhaustion, coincident with the cessation of lipid accumulation. In contrast, ME in Mortierella alpina, a fungus capable of accumulating 50% (w/w, dry wt) lipid, remains active for over 60 h after N-exhaustion during which time lipid accumulation continues. No other enzyme activity studied, including the lipogenic enzymes acetyl-CoA carboxylase, fatty acid synthase, diacyglycerol acyltransferase, ATP: citrate lyase and the NADPH-generating enzymes glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP+:isocitrate dehydrogenase, demonstrated any correlation with the accumulation of storage lipid in either fungus. Full activity of ME is restored in Mr. circinelloides within 4 h by adding NH4+ to the cultures, but this is prevented by adding cycloheximide as an inhibitor of protein synthesis. This suggests that the decrease in ME activity occurs due to down-regulation of the ME gene.
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PMID:The role of malic enzyme in the regulation of lipid accumulation in filamentous fungi. 1046 57

The relationship between the activities of 3 cytosolic enzymes with aflatoxin biosynthesis in Aspergillus parasiticus cultured under different conditions has been investigated in order to find out the role of each enzyme in aflatoxin biosynthesis. Basically the activity of isocitrate dehydrogenase (IDH) was higher in non-toxigenic strains as compared to its counterpart toxigenic fungi (p < 0.05). In contrast, the activities of fatty acid synthase (FAS) as well as glutathione S-transferase (GST) were higher (P < 0.05) in toxigenic strains than that of the non-toxigenic fungi. Aflatoxin production was inhibited in fungi grown in presence of various concentrations of neem leaf extract. Aflatoxin was at its lowest level (>90% inhibition) when the concentration of neem extract was adjusted to 50% (v/v). No significant changes in FAS and IDH activities were observed when aflatoxin synthesis was under restraints by neem (Azadirachta indica) leaf extract. During a certain period of time of culture growth, when aflatoxin production reached to its maximum level, the activity of FAS was slightly induced in the toxigenic strains fed with a low concentration (1.56% v/v) of the neem leaf extract. At the time (96 h) when aflatoxin concentration reached to its maximum levels, the activity of GST in the toxigenic fungi was significantly higher (i.e., 7-11 folds) than that of non-toxigenic strains. The difference was highest in mycelial samples collected after 120 h. However unlike FAS and IDH, GST was readily inhibited (approximately 67%) in mycelia fed with 1.56% v/v of the neem extract. The inhibition reached to maximum of 80% in samples exposed to 6.25-12.5% of the extract. These results further substantiate previous finding that there is a positive correlation between GST activity and aflatoxin production in fungi.
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PMID:Effects of neem leaf extract on production of aflatoxins and activities of fatty acid synthetase, isocitrate dehydrogenase and glutathione S-transferase in Aspergillus parasiticus. 1208 4

A small number of eukaryotic micro-organisms, the oleaginous species, can accumulate triacylglycerols as cellular storage lipids, sometimes up to 70% of the biomass. Some of these lipids, particularly those containing high proportions of polyunsaturated fatty acids of nutritional and dietary importance, are now in commercial production; these are known as single-cell oils. The biochemistry of lipid accumulation has been investigated in yeasts and filamentous fungi and can now be described in some detail: lipid accumulation is triggered by cells exhausting nitrogen from the culture medium, but glucose continues to be assimilated. Activity of isocitrate dehydrogenase within the mitochondrion, however, now slows or even stops due to the diminution of AMP within the cells. This leads to the accumulation of citrate, which is transported into the cytosol and cleaved to acetyl-CoA by ATP:citrate lyase, an enzyme that does not occur in non-oleaginous species. This enzyme is therefore essential for lipid accumulation. The presence of this enzyme does not, however, explain why different species of oleaginous micro-organisms have different capacities for lipid accumulation. The extent of lipid accumulation is considered to be controlled by the activity of malic enzyme (ME), which acts as the sole source of NADPH for fatty acid synthase (FAS). If ME is inhibited, or genetically disabled, then lipid accumulation is very low. There is no general pool of NADPH which can otherwise be used by FAS. The stability of ME is therefore crucial and it is proposed that ME is physically attached to FAS as part of the lipogenic metabolon. ME activity correlates closely with lipid accumulation in two filamentous fungi, Mucor circinelloides and Mortierella alpina. When ME ceases to be active, lipid accumulation also stops. No other enzyme activity shows such a correlation.
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PMID:Regulation of lipid accumulation in oleaginous micro-organisms. 1244 Sep 69

The effects of sex, genotype, and adipose depot on lipogenic enzyme activity have been investigated in Holstein and Pirenaican bulls and heifers, taking into account differences in adipocyte size. Fifteen Pirenaican bulls and 15 heifers and 15 Holstein bulls and 13 heifers were fattened until slaughter (12 to 13 mo old and 450 to 500 kg of body weight). During the fattening period, animals had ad libitum access to commercial concentrates and straw. The 10th rib was dissected to determine the fat content. Adipocyte size and activities of the following lipogenic enzymes were determined: glycerol 3-phosphate dehydrogenase, fatty acid synthase, nicotinamide adenine dinucleotide phosphate (NADP)-malate dehydrogenase, glucose 6-phosphate dehydrogenase, and NADP-isocitrate dehydrogenase, in the omental, perirenal, subcutaneous, and intermuscular adipose depots, respectively. Because adipocyte mean cell volume varied with sex, breed, and depot, regression analyses of log(e) activity per cell and log(e) cell volume were used to compare activities per unit volume. Sex, breed and depot had no effect (P > 0.05) on the gradients of regressions, which did not differ significantly from 1. Thus, activity per unit volume did not vary with cell size. Consequently, sex, breed, and depot effects on the regression analyses were equivalent to effects on activity per unit volume. Females had greater amounts of fat in the 10th rib (P < 0.001), larger adipocytes (P < 0.001) and, in general, greater (P < 0.05) lipogenic activity per cell, even when adjusted for cell size, than males. These findings suggest that differences in adiposity between sexes are mainly due to females having a greater capacity for lipid synthesis, and hence, hypertrophy, than males. When adjusted for differences in carcass weight, Holsteins had larger adipocytes than Pirenaicans. The abdominal depots, omental and perirenal, had a greater adipocyte size (P < 0.001) and, in general, greater lipogenic enzyme activities per cell (P < 0.05) than the subcutaneous and intermuscular carcass depots. However, when activity per cell was adjusted for cell size, subcutaneous depots had greater fatty acid synthae, glucose 6-phosphate dehydrogenase, and NADP-malate dehydrogenase activities than omental and perirenal, indicating that other factors such as nutrient supply may restrict hypertrophy of carcass adipocytes.
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PMID:Lipogenic enzyme activities in different adipose depots of Pirenaican and Holstein bulls and heifers taking into account adipocyte size. 1264 87

Sodium-orthovanadate (SOV) and seed powder of Trigonella foenum graecum Linn. (common name: fenugreek, family: Fabaceae) (TSP) besides being potential hypoglycemic agents have also been shown to ameliorate altered lipid metabolism during diabetes. This study evaluates the short-term effect of oral administration of SOV and TSP separately and in concert (for 21 days) on total lipid profile and lipogenic enzymes in tissues of alloxan diabetic rats. Diabetic rats showed 4-fold increase in blood glucose. The level of total lipids, triglycerides and total cholesterol in blood serum increased significantly during diabetes. During diabetes the level of total lipids increased significantly (P < 0.001) in liver and in kidney by 48% and 55%, respectively, compared to control. Triglycerides level increased by 32% (P < 0.01) in liver and by 51% (P < 0.005) in kidney, respectively, compared to control. Total cholesterol level also increased significantly in both liver and kidney (P < 0.01 and P < 0.001, respectively). The activities of NADP-linked enzymes; namely glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and the activities of lipogenic enzymes namely ATP-citrate lyase (ATP-CL) and fatty acid synthase (FAS) were decreased significantly in liver and increased in kidney during diabetes as compared to control. SOV and TSP administration to diabetic animals prevented the development of hyperglycemia and alteration in lipid profile in plasma and tissues and maintained it near normal. Maximum prevention was observed in the combined treatment with lower dose of SOV (0.2%) after 21 days. We are presenting for the first time effectiveness of combined treatment of SOV and TSP in amelioration of altered lipid metabolism during experimental type-I diabetes.
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PMID:Effects of sodium-orthovanadate and Trigonella foenum-graecum seeds on hepatic and renal lipogenic enzymes and lipid profile during alloxan diabetes. 1528 7

The purpose of this experiment was to determine the possible relationship between certain indices of lipid metabolism and specific gene expression in chickens fed methimazole to simulate hypothyroidism. Male broiler chickens (Gallus gallus) growing from 7 to 28 days of age were fed diets containing 18% crude protein and either 0 or 1 g methimazole per kilogram of diet. At 28 days, these two groups were further subdivided into groups receiving 18% crude protein diets containing either 0 or 1 mg triiodothyronine (T3) per kilogram. Birds were sampled at 28, 30, and 33 days. Measurements taken included in vitro lipogenesis (IVL), malic enzyme (ME) activity, isocitrate dehydrogenase, aspartate amino transferase, and the expression of the genes for ME, fatty acid synthase (FAS), and acetyl coenzyme carboxylase (ACC). Hypothyroidism decreased IVL and ME at 28 days of age; however, T3 supplementation for 2 days restored both IVL and ME. Paradoxically, continuing T3 replenishment for an additional 3 days decreased IVL but did not decrease ME activity. In contrast, supplemental T3 decreased IVL in euthyroid birds, regardless of the dosing interval, but had no effect on ME activity. Although methimazole decreased ME gene expression, there was only a transitory relationship between enzyme activity and gene expression when plasma T3 was restored with exogenous T3. These data may help to explain some of the apparent reported dichotomies in lipid metabolism elicited by changes in the thyroid state of animals. In addition, most metabolic changes in response to feeding T3 occurred within 2 to 5 days, suggesting that changes in intermediary metabolism preceded morphological changes. In conclusion, the thyroid state of the animal will determine responses to exogenous T3.
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PMID:Methimazole, thyroid hormone replacement, and lipogenic enzyme gene expression in broilers. 1568 26


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