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:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetanic stimulation of fibers in the hippocampal slice preparation produces long-term potentiation (LTP) and also decreases the in vitro incorporation of phosphate into the alpha subunit of pyruvate dehydrogenase (alpha PDH). This paper describes 6 experiments that were undertaken to replicate this observation. Hippocampal slices were incubated in a specially designed chamber and stimulated with a tungsten wire electrode in the stratum radiatum for 1 s at 100 Hz. Two minutes after the tetanus, the stimulated slices were removed alternately with control (not tetanized) slices and each group was pooled for subcellular fractionation and labeling of the fractions with [32P]ATP. Proteins were separated by electrophoresis and relative 32P contents of 41K and 50K protein bands were studied. Tetanic stimulation of the stratum radiatum did not affect subsequent phosphorylation of a 50K Mr protein that has been reported to be altered by perforant path activation. Stimulation also had no effect on pyruvate dehydrogenase enzyme activity or on the ratio of active (dephosphorylated) to inactive enzyme. In most cases tetanic stimulation produced no significant change in the in vitro phosphorylation of this enzyme. Only under one set of conditions, labeling with 250 microM [gamma-32P]ATP for 10 s, was a decrease in the in vitro labeling of alpha PDH shown to be statistically significant. These findings suggest that LTP is not necessarily accompanied by an initial change in PDH phosphorylation level or activity but may be associated with a decrease in the kinase activity directed toward this protein.
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PMID:Long-term potentiation in the hippocampal slice: possible involvement of pyruvate dehydrogenase. 673

Pyruvate and palmitate oxidations by cultured fibroblasts suspensions were measured in optimized conditions and proved to be within normal range in the cells from Friedreich's patients. However, when pyruvate oxidation was measured by direct assay of the pyruvate dehydrogenase complex, this enzyme activity proved to be significantly lower in Friedreich's than in controls' cells. These abnormalities were not observed when the cells were sonicated. Moreover, lipoamide dehydrogenase activity. Km and Vmax were within the normal range in Friedreich's cells. These data suggest that the low activities of the PDH complex are not a primary defect in Friedreich's ataxia, but are more likely related to membrane abnormalities in Friedreich's cells.
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PMID:Friedreich's ataxia in northern Italy. II. Biochemical studies in cultured cells. 689 62

Pyruvate and palmitate oxidations by cultured fibroblast suspensions were measured in optimized conditions and proved to be within normal range in the cells from Friedreich's patients. But when pyruvate oxidation was measured by direct assay of the pyruvate dehydrogenase complex, this enzyme activity proved to be significantly lower in Friedreich's than in controls' cells. These abnormalities were not observed when the cells were sonicated. Moreover, lipoamide dehydrogenase activity Km and Vmax were within the normal range in Friedreich's cells. These data suggest that the low activities of the PDH complex are not a primary defect in Friedreich's ataxia but are more likely to be related to membrane abnormalities in Friedreich's cells.
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PMID:Friedreich's ataxia II. Biochemical studies in cultured cells. 689 44

Changes in the neuron metabolism in the hippocampal slices following stimulation and potentiation (induction of increase of the evoked extracellular potential) of Schaffer collaterals-pyramidal cell synapses were tested with 2-deoxyglucose (2DG) technique. 2DG uptake was used as an index of glucose utilization. Stimulation evoked calcium- and frequency-dependent increase in [3H]2DG uptake. Potentiation of the synaptic response increased [3H]2DG accumulation but only when potentiated synapses were pressed to be active. It is suggested that stimulation-dependent increase in [3H]2DG uptake is mainly related to neurotransmission. Potentiation-dependent increase of [3H]2DG uptake is probably due to phosphorylation (inhibition) of pyruvate dehydrogenase (PHD). Inactivation of PDH may partially change the nerve endings metabolism from the aerobic pathway into anaerobic. To get the same amount of energy after potentiation as before, the nerve endings have to increase the rate of metabolism.
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PMID:Changes in the hippocampal slices energy metabolism following stimulation and long-term potentiation of Schaffer collaterals-pyramidal cell synapses tested with the 2-deoxyglucose technique. 708 5

The effect of in vivo exposure to a sublethal concentration of hexavalent chromium for 30 days on blood glucose, blood liver and muscle lactic acid; haemoglobin, liver and muscle glycogen; and activities of lactate dehydrogenase (LDH), pyruvate dehydrogenase (PHD) and succinate dehydrogenase (SDH) in liver, muscle, kidney, gills and brain has been studied. Blood glucose and lactic acid levels were elevated. Liver glycogen was depleted but muscle glycogen content increase. The activities of LDH and SDH in liver were elevate. Elevation was also observed in muscle LDH and PDH activities, showing that the rate of glycolysis is increased. No change was noted in haemoglobin content of blood or in the activities of the three dehydrogenases in kidney and gills.
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PMID:Toxic effects of chromium in a freshwater teleost fish, Channa punctatus. 709 8

Changes in the activity of pyruvate dehydrogenase [pyruvate:lipoamide oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1, PDH], elicited by inhibition of the phosphorylation of its 40,000 Mr alpha-subunit, were compared with changes in pyruvate-supported calcium accumulation by rat brain mitochondria. Dichloroacetate (DCA) produces concentration-dependent inhibition of the phosphorylation of intramitochondrial PDH alpha-subunit, which is accompanied by stimulation of PDH activity and calcium accumulation. DCA did not affect succinate- or ATP-supported mitochondrial calcium accumulation. The concentration of DCA giving half-maximal inhibition of the phosphorylation was almost identical to that giving half-maximal stimulation of PDH activity and calcium accumulation. PDH activity and pyruvate-supported calcium accumulation showed similar dependence on pyruvate concentration with respective apparent affinities for pyruvate of 40 microM and 30 microM, and both activities exhibited positive cooperativity. DCA modified only the maximal activity of PDH or the maximal calcium DCA modified only the maximal activity of PDH or the maximal calcium accumulation without changing either the apparent affinities for pyruvate or calcium or the Hill coefficients. These data provide evidence that calcium accumulation by mitochondria is tightly linked to PDH activity and that changes in the phosphorylation of the PDH alpha-subunit can be reflected in changes in the calcium-buffering ability of mitochondria. This suggests a possible mechanism by which a variety of manipulations, such as repetitive synaptic stimulation, can alter the regulation of internal calcium levels.
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PMID:Phosphorylation-mediated changes in pyruvate dehydrogenase activity influence pyruvate-supported calcium accumulation by brain mitochondria. 724 Nov 45

Isogenic strains of Escherichia coli W3110 containing pyruvate dehydrogenase complexes with three (wild-type), two or one lipoyl domains per lipoate acetyltransferase (E2p) chain, were constructed. The maximum growth rates (mumax) for batch cultures growing in minimal medium containing different carbon sources showed that reducing the number of lipoyl domains adversely mumax value of the mutant containing one lipoyl domain per E2p chain was restored by the presence of compatible multicopy plasmids encoding PDH complexes with either one or three lipoyl domains per E2p chain. In glucose-limited chemostat cultures the protein contents of all strains were similar and substrate carbon was totally accounted for in the biomass and CO2 produced. However, the carbon efficiencies (percentage carbon conversion to biomass) were significantly lower when the lipoyl domain content of the E2p subunit was reduced from three to one. Similarly, the cellular maintenance energy (m(e)) and the maximum growth yield (Ymax) were lower in bacteria containing PDH complexes with fewer than three lipoyl domains per E2p chain. Wild-type values were restored by supplementing the medium with either casamino acids (0.01%) or acetate (up to 0.1 mM). The lower growth efficiencies of the mutants were further confirmed in competition experiments where equal numbers of genetically marked (NalR) mutant and wild-type bacteria were used to inoculate glucose-limited chemostat cultures (dilution rate 0.075 h-1). The mutants with one or two lipoyl domains per E2p chain were washed out, whereas in controls, the initial ratio of wild-type (Nals) to reconstructed wild-type (NalR) bacteria was maintained over 50 generations.
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PMID:Metabolic engineering in Escherichia coli: lowering the lipoyl domain content of the pyruvate dehydrogenase complex adversely affects the growth rate and yield. 755 Oct 48

Prolactin is an important regulator of prostate citrate production. In rats this regulatory effect of prolactin is specific for lateral prostate, and has no effect on either ventral or dorsal prostate. The mechanisms by which prolactin regulates prostate citrate production have not been elucidated. Two key regulatory enzymes involved in citrate synthesis by prostate epithelial cells are mitochondrial aspartate aminotransferase (mAAT) which provides oxalacetate, and PDH E1 alpha (pyruvate dehydrogenase) which provides acetyl CoA for citrate synthesis. Our previous studies demonstrated that prolactin regulates mAAT. However, an increase in citrate synthesis would require an increase in both oxalacetate and acetyl CoA. Therefore, we investigated the possibility that prolactin might also regulate PDH E1 alpha in LP epithelial cells. The present studies demonstrate that prolactin administration (1 mg/rat) to rats resulted in an increased level of E1 alpha in LP epithelial cells within 6 hr, but had no effect on the E1 alpha level of VP epithelial cells. In vitro studies demonstrated that exposure of freshly prepared LP epithelial cells to prolactin (0.1-1.0 microgram/ml) resulted in increased levels of E1 alpha. Prolactin had no effect on either VP or DP epithelial cells. The stimulatory effect of prolactin on E1 alpha was inhibited by actinomycin and cycloheximide, thereby indicating that prolactin stimulated the biosynthesis of E1 alpha. The studies reveal that prolactin specifically stimulates E1 alpha levels of LP epithelial cells, whereas testosterone specifically stimulates E1 alpha levels of VP epithelial cells. At this time, we propose that the effects of prolactin and testosterone involve increased expression of the E1 alpha gene of LP and VP epithelial cells, respectively.
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PMID:Prolactin specifically increases pyruvate dehydrogenase E1 alpha in rat lateral prostate epithelial cells. 771 83

Epidermis exhibits glycolytic features peculiar to cancer cells. The activity of pyruvate dehydrogenase complex, both active (PDHa) and total (PDHt) forms, has been investigated and compared in epidermis and epidermal carcinomas from human source. Low or undetectable PDHa is found in either normal and neoplastic tissue. PDHt is unchanged in human epidermis between the second and seventh decades of life but is dramatically decreased following neoplastic transformation (0.107 and 0.026 units/g fresh tissue for epidermis and epidermal carcinoma, respectively). As PDH plays a key role in mitochondrial carbohydrate metabolism, the decrease of total enzymic capacity found in tumors suggest that different mechanisms regulate PDH expression and, in turn, glycolytic mechanisms of epidermis and cancer cells.
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PMID:Transformation linked decrease of pyruvate dehydrogenase complex in human epidermis. 795 43

In this review, we evaluate the relative regulatory importance of specific strategic enzymes (in particular glycogen synthase, acetyl-CoA carboxylase [ACC] and the pyruvate dehydrogenase complex [PDH]) for carbohydrate utilization as an anabolic precursor and as an energy substrate during the nutritional transitions between the fed and fasted states. The involvement of the specific protein kinases contributing to the inactivation of these enzymes by phosphorylation [cyclic AMP-dependent protein kinase, AMP-activated protein kinase and PDH kinase] in achieving each regulatory response is also assessed. We demonstrate a striking temporal correlation between hepatic glycogen mobilization and PDH and ACC inactivation by phosphorylation during the immediate postabsorptive period; in contrast, rates of hepatic glycogen synthesis and PDH and ACC expressed activities do not change in parallel during refeeding. The results are consistent with shifting of the primary sites of control for overall hepatic carbon flux during the fed-to-starved and starved-to-fed nutritional transitions achieved, at least in part, by a complex pattern of regulation by protein phosphorylation and metabolites which is critically dependent on the precise nutritional status. Data are also presented that demonstrate asynchronous suppression of glucose uptake/phosphorylation and pyruvate oxidation in cardiac and skeletal muscle during progressive starvation. Analogous asynchrony is observed in the reactivation of these processes in cardiac and skeletal muscle during refeeding after starvation. We provide evidence in support of the concept that selective suppression of pyruvate oxidation in oxidative muscles during early starvation and during the initial phase of refeeding is achieved because of differential sensitivity of glucose uptake/phosphorylation and pyruvate oxidation to lipid-fuel utilization. We discuss the relative importance of regulatory events governing local fatty acid production and utilization (via lipoprotein lipase and carnitine palmitoyltransferase 1, respectively) or overall fatty acid supply (dictated by events at the adipocyte) for fuel utilization by muscle during nutritional transitions. Finally, we assess the regulatory importance of glycogen synthesis in determining overall rates of glucose clearance by skeletal muscle during alimentary hyperglycemia and hyperinsulinemia.
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PMID:Mechanisms involved in the coordinate regulation of strategic enzymes of glucose metabolism. 810 32


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