Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypoglycemic sulfonylurea gliquidone, used at a 10 microM concentration, failed to affect the metabolism of D-glucose in rat pancreatic islets incubated in the presence of 5.6 mM, 8.3 mM or 16.7 mM D-glucose. However, at 2.8 mM D-glucose, gliquidone increased D-[U-14C]glucose oxidation while decreasing the utilization of D-[5-3H]glucose and generation of radioactive acidic metabolites and amino acids from D-[U-14C]glucose. These dissociated effects could conceivably be attributable, respectively, to activation of FAD-linked glycerophosphate dehydrogenase as a result of an increase in cytosolic Ca2+ concentration and to a subsequent inhibition of phosphofructokinase as a result of an increase in cytosolic ATP concentration. The effect of gliquidone on the paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization was indeed duplicated by repaglinide and suppressed in the absence of extracellular Ca2+ or at low temperature. The present findings thus provide a further illustration of the often contrasting effects of pharmacological and physiological insulinotropic agents on selected metabolic, cationic and functional variables in pancreatic islet cells.
Res Commun Mol Pathol Pharmacol 1998 Nov
PMID:Effects of gliquidone on D-glucose metabolism in rat pancreatic islets depend on hexose concentration. 1010 May 2

The localisation of diaphorase was visualised by light microscopy using the dye nitro blue tetrazolium and NADPH as substrates. Under appropriate conditions, diaphorase reduces this dye to a dark blue insoluble formazan. The enzyme was located at very low activity in many tissue and glandular structures of the deer, but at very much higher activity in sebaceous glands in the dermal velvet of the antler and skin, and in additional sebaceous gland-related structures in the ear canal, prepuce and tail (scent) gland. Within sebaceous glands, activity was greatest in the outermost layers of the acini, but decreased as the cells progressed and differentiated centripetally. There was little or no difference between the staining observed when NADH was used as a substrate, compared to NADPH. There was generalised staining (usually light) for glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and glycerol-3-phosphate dehydrogenase. However, this staining was not specifically localised to sebaceous glands and related structures, showing that the observed activity in these structures was due to a diaphorase that was distinct from any of the dehydrogenase activities tested. The possible role of diaphorase in sebaceous development and secretion is discussed.
Comp Biochem Physiol B Biochem Mol Biol 1999 May
PMID:Diaphorase activity in sebaceous glands and related structures of the male red deer. 1042 9

Treatment of intact C3H10T1/2 cells or microsomes therefrom with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzanthracene (BA) enhanced CYP1B1 activity and CYP1B1 expression as revealed by elevations of CYP1B1-catalyzed DMBA metabolism, CYP1B1 apoprotein level and CYP1B1 gene expression. One hundred microM DHEA caused an 80-90% inhibition of cellular DMBA metabolism without inflicting cell death. Cytosolic glucose-6-phosphate dehydrogenase (G6PDH) was also inhibited in DHEA-treated cells, presumably due to the inhibition of NADP reduction. In contrast, neither DMBA metabolism nor CYP1B1 apoprotein was inhibited by DHEA in the microsomes isolated from these cells. DHEA (100 microM), TCDD (10 nM) and BA (10 microM) stimulated the activities and increased the apoprotein levels of two peroxisomal enzymes, namely, acyl CoA oxidase (ACOX) and acyl CoA hydrolase (ACH2) and also induced the expression of CYP1B1 and ACOX genes. Cytosolic fatty acyl-CoA beta-oxidation was also stimulated by DHEA, TCDD and BA. In corroboratory experiments, it was found that concomitant with the stimulation of the activity of a key enzyme regulator of fatty acid homeostasis, namely, glycerol-3-phosphate dehydrogenase (G3PDH), these agents enhanced arachidonic acid (AA) metabolism as judged by the release of [3H] from AA into the culture medium. Collectively, these data suggest that DHEA mediates the regulation of CYP1B1 and inhibits BA and TCDD-induced CYP1B1-catalyzed carcinogen (DMBA) activation in 10T1/2 cells through metabolic interactions that involve the activation of the peroxisomal and fatty acid beta-oxidation signaling pathways. These results also present evidence for the first time, for the possible peroxisomal effects of TCDD and BA which are similar to those of DHEA in this mouse embryo fibroblast cell line.
Mol Cell Biochem 1999 Aug
PMID:Evidence for the involvement of the fatty acid and peroxisomal beta-oxidation pathways in the inhibition by dehydroepiandrosterone (DHEA) and induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benz(a)anthracene (BA) of cytochrome P4501B1 (CYP1B1) in mouse embryo fibroblasts (C3H10T1/2 cells). 1049 82

Thyroid hormone can potentially regulate the malate/aspartate and alpha-glycerophosphate shuttle pathways in cardiac mitochondria either directly, by altering gene expression, or indirectly, by increasing myocardial workload. The goal of the current study was to determine the influence of thyroid hormone on the NADH shuttles in cardiac and liver mitochondria. Malate/aspartate and alpha-glycerophosphate shuttle capacities were significantly increased in cardiac mitochondria from adult rats treated for 9 days with T3 compared to saline-treated controls. Liver mitochondria demonstrated a significant increase in alpha-glycerophosphate and no change in malate/aspartate shuttle capacity. T3 increased steady-state mRNA levels and activity of mitochondrial alpha-glycerophosphate dehydrogenase in both myocardium and liver. Quantitative immunoblot studies demonstrated a significant increase in aspartate-glutamate carrier levels in T3-treated myocardium suggesting a regulatory role of the aspartate/glutamate carrier in T3-treated hearts. Thyroid hormone effects on the NADH shuttles are tissue-specific. Changes in the NADH shuttles in the presence of thyroid hormone excess occur both directly at the gene level and indirectly as an adaptive response.
J Mol Cell Cardiol 2000 Jan
PMID:Thyroid hormone regulation of the NADH shuttles in liver and cardiac mitochondria. 1065 85

The acute and chronic effects of tumour necrosis factor-alpha (TNF-alpha) on leptin production by human preadipocytes, differentiated preadipocytes, and mature adipocytes have been examined by competitive RT-PCR of leptin mRNA and by western blotting. In preadipocytes, secreted leptin was detectable after 5-day incubation in differentiation medium and this increased 4-fold by day 20. TNF-alpha blocked leptin synthesis during differentiation. In differentiated preadipocytes and mature adipocytes, TNF-alpha treatment resulted in time-dependent decreases in mRNA for leptin and glycerol-3-phosphate dehydrogenase (G3PD). In contrast, TNF-alpha (4-8-h treatment) resulted in a 4-fold increase in leptin release. This effect was lost at 24 h and leptin accumulation in culture medium was decreased 24-48 h after TNF-alpha addition. We conclude that TNF-alpha stimulates the release of preformed leptin from human mature adipocytes and existing differentiated preadipocytes, which may contribute to obesity/infection-linked hyperleptinemia, and that TNF-alpha inhibits leptin synthesis via inhibition of preadipocyte differentiation and induction of adipocyte dedifferentiation.
Mol Cell Endocrinol 2000 Jan 25
PMID:Tumour necrosis factor-alpha exerts dual effects on human adipose leptin synthesis and release. 1068 54

Glycolysis is the only ATP-generating process in bloodstream form trypanosomes and is therefore a promising drug target. Inhibitors which decrease significantly the glycolytic flux will kill the parasites. Both computer simulation and experimental studies of glycolysis in bloodstream form Trypanosoma brucei indicated that the control of the glycolytic flux is shared by several steps in the pathway. The results of these analyses provide quantitative information about the prospects of decreasing the flux by inhibition of any individual enzyme. The plasma membrane glucose transporter appears the most promising target from this perspective, followed by aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and glycerol-3-phosphate dehydrogenase. Non-competitive or irreversible inhibitors would be most effective, but it is argued that potent competitive inhibitors can be suitable, provided that the concentration of the competing substrate cannot increase unrestrictedly. Such is the case for inhibitors that compete with coenzymes or with blood glucose.
Mol Biochem Parasitol 2000 Feb 25
PMID:Metabolic control analysis of glycolysis in trypanosomes as an approach to improve selectivity and effectiveness of drugs. 1074 6

Different doses of vitamin B12 (0.25, 0.5, 1, 2 and 4 micrograms/g, injected intraperitoneally for three consecutive days) altered the activities of mitochondrial-alpha-glycerophosphate dehydrogenase (alpha-GPD) and NADP-dependent cytosolic malic enzyme (ME) in the brain of singi fish. The alpha-GPD activity increased at doses of 0.5, 1, 2 and 4 micrograms/g vitamin B12. A dose of 0.5 microgram/g vitamin B12 induced less activity than higher doses. ME activity increased with 1, 2 and 4 micrograms/g of vitamin B12/g. The mitochondrial and cytosolic protein content remained unchanged after vitamin B12 administration. Cycloheximide treatment inhibited the vitamin B12-induced increase in alpha-GPD and ME activity. Thus, vitamin B12 is involved in the induction of some enzymes in fish brain.
Comp Biochem Physiol B Biochem Mol Biol 2000 Apr
PMID:Vitamin B12-induced alterations in activities of alpha-glycerophosphate dehydrogenase and malic enzyme in brain of singi fish, Heteropneustes fossilis (Bloch). 1090 58

Membrane potential-dependent ATP production was measured in mitochondrial fractions of procyclic Trypanosoma brucei using a luciferase based assay. Mitochondria isolated under hypotonic conditions were able to produce ATP using succinate as substrate. The same was observed with mitochondria isolated under isotonic conditions, however, in this case a 6-7-fold higher amount of ATP was produced with glycerol-3-phosphate as substrate. Disruption of the outer membrane of isotonically prepared mitochondria lead to a selective loss of the glycerol-3 phosphate induced ATP production, indicating that glycerol-3-phosphate dehydrogenase is a soluble enzyme of the intermembrane space. Isolation of mitochondria under hypotonic conditions, therefore, results in disruption of the outer membrane, whereas in the organelles isolated under isotonic conditions both the membranes remain intact.
Mol Biochem Parasitol 2000 Nov
PMID:ATP production in isolated mitochondria of procyclic Trypanosoma brucei. 1108 19

FAD-dependent glycerol-3-phosphate dehydrogenase (mGPD) enzyme is located in the mitochondrial inner membrane where it catalyzes irreversible oxidation reactions. Type 2 diabetes mellitus (DM) is a multifactorial disorder associated with physiological abnormalities in the glycerol and free fatty acids (FFA) metabolic pathways. In the present study, we have evaluated the association among the mGPD H264R sequence variation and postabsorptive plasma FFA and glycerol concentrations in a sample of French Canadians with and without type 2 DM. A sample of 81 recently diagnosed type 2 DM and 318 nondiabetic, nonobese, normotriglyceridemic French Canadians were screened for the presence of the mGPD H264R genetic variant using a PCR-RFLP-based method. The 318 nondiabetic subjects were free of known type 2 DM covariates (fasting glucose <7.0 mmol/L, body mass index <29 kg/m(2), fasting glycerol <2.0 mmol/L and absence of the N288D sequence variation in the glycerol kinase gene, fasting triglyceride <2.5 mmol/L). The association of mGPD H264R sequence variation with plasma FFA and glycerol concentrations was assessed in different regression models. Among non-DM individuals, the R allele (HR and RR genotypes) was associated with increased plasma FFA and glycerol concentrations (P < 0.05). However, the mean plasma FFA and glycerol concentrations were not affected by the H264R genotype in the type 2 DM sample. Overall, mean plasma FFA concentrations in non-DM RR homozygotes reached values that were similar to those achieved in patients with type 2 diabetes (0.87 +/- 0.63 vs 0.90 +/- 0.48 mmol/L). After controlling for age, gender, body mass index, fasting glucose, and fasting triglyceride concentrations, the relative odds of having fasting plasma FFA levels above the 90th percentile (0.9 mmol/L) in the absence of DM was increased by twofold in H264R heterozygotes (P = 0.04) and fourfold among R264 homozygotes (P = 0.009) compared to noncarriers. In the absence of DM, the mGPD R allele was also associated with higher plasma glycerol concentrations (P < 0.05). Results in non-DM individuals suggest that the mGPD R allele is associated with DM intermediate phenotypes. The absence of a relation between mGPD genotype and DM is in accordance with the view that DM is a complex phenotype in which increased plasma FFA or glycerol concentrations result from metabolic alterations which might obscure the effect of the mGPD polymorphism.
Mol Genet Metab 2001 Mar
PMID:A sequence variation in the mitochondrial glycerol-3-phosphate dehydrogenase gene is associated with increased plasma glycerol and free fatty acid concentrations among French Canadians. 1124 26

Rainbow smelt (Osmerus mordax) can accumulate extreme levels of glycerol in their blood during winter. Low temperatures are required for glycerol accumulation in smelt blood and the enzyme glycerol-3-phosphate dehydrogenase (GPDH) has been suggested to play a role in glycerol production/concentration in this species. In the present study, cDNA sequences encoding glycerol-3-phosphate dehydrogenase (GPDH) from rainbow smelt and Atlantic salmon (Salmo salar) were cloned. The encoded GPDH protein sequences were very similar to one another (88% identity). Using RT-PCR, GPDH mRNA was detected in skin, gill, heart, head kidney, brain and liver from both salmon and smelt obtained in December. However, GPDH was not detected in salmon intestine and spleen or in smelt intestine. Examination of GPDH expression in smelt liver during February by Northern blotting revealed temperature regulation. Elevation of the temperature resulted in a significant decrease in liver GPDH transcript level. Serum glycerol levels decreased concomitantly. These findings suggest a role for GPDH in the accumulation of glycerol in smelt at low temperatures.
Comp Biochem Physiol B Biochem Mol Biol 2001 Mar
PMID:Cloning of glycerol-3-phosphate dehydrogenase cDNAs from two fish species and effect of temperature on enzyme expression in rainbow smelt (Osmerus mordax). 1125 May 35


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