Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.1 (pyruvate carboxylase)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of phenylalanine and phenylpyruvate on the metabolism of pyruvate by isolated mitochondria from rat brain was investigated. 2. Phenylpyruvate inhibited the fixation of H(14)CO(3) (-) in the presence of pyruvate by intact rat brain mitochondria, whereas phenylalanine and other metabolites of this amino acid had no inhibitory effect on this process. 3. Pyruvate carboxylase activity in freeze-dried rat brain mitochondrial preparations was also inhibited only by phenylpyruvate, and a ;mixed type' inhibition was observed. 4. The K(m) for pyruvate of rat brain pyruvate carboxylase was about 0.2mm. 5. The concentration of phenylpyruvate required for a 50% inhibition of H(14)CO(3) (-) fixation by the intact mitochondria and of pyruvate carboxylase activity was dependent on the concentration of pyruvate used in the incubation medium. 6. The possible significance of inhibition of pyruvate carboxylase activity by phenylpyruvate in the brains of phenylketonuric patients is discussed.
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PMID:The effect of phenylpyruvate on pyruvate metabolism in rat brain. 463 34

In isotopic experiments, the labeling pattern of glutamate opens a window on hepatic metabolism, particularly the citric acid cycle, gluconeogenesis and fatty acid oxidation. This is because glutamate is in isotopic equilibrium with alpha-ketoglutarate, whose labeling pattern is influenced by the following: 1) the contributions of glucose and fatty acids to acetyl-CoA, 2) the relative contributions of pyruvate carboxylase and pyruvate dehydrogenase to the entry of pyruvate carbon into the citric acid cycle, and 3) the rate of gluconeogenesis in relation to citric acid cycle activity. In humans and primates, hepatic glutamate can be sampled noninvasively via urinary phenylacetylglutamine, which is formed in liver from phenylacetate (a side product of phenylalanine catabolism) and glutamine (which equilibrates with liver glutamate and alpha-ketoglutarate). The (14)C- or (13)C-labeling pattern of the glutamate moiety of phenylacetylglutamine can be measured by sequential degradations to (14)CO(2), gas chromatography-mass spectrometry or nuclear magnetic resonance (NMR). When phenylacetylglutamine is labeled from singly labeled [(14)C]- or [(13)C]substrates, relative metabolic rates can be computed from the labeling pattern using Landau's model. In diabetic patients infused with [3-(13)C]pyruvate, the noninvasive sampling of hepatic glutamate via phenylacetylglutamine allows one to test the degree of liver insulinization via the (pyruvate carboxylase)/(pyruvate dehydrogenase) activity ratio. This ratio regulates gluconeogenesis in part. Its measurement may allow the identification of patients who might benefit from the intraperitoneal administration of insulin, or from recently developed antidiabetic drugs.
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PMID:Glutamate, a window on liver intermediary metabolism. 1073 68

Evidence is presented that, in Methanosarcina barkeri oxaloacetate synthesis, an essential and major CO(2) fixation reaction is catalyzed by an apparent alpha(4)beta(4)-type acetyl coenzyme A-independent pyruvate carboxylase (PYC), composed of 64.2-kDa biotinylated and 52.9-kDa ATP-binding subunits. The purified enzyme was most active at 70 degrees C, insensitive to aspartate and glutamate, mildly inhibited by alpha-ketoglutarate, and severely inhibited by ATP, ADP, and excess Mg(2+). It showed negative cooperativity towards bicarbonate at 70 degrees C but not at 37 degrees C. The organism expressed holo-PYC without an external supply of biotin and, thus, synthesized biotin. pycA, pycB, and a putative bpl gene formed a novel operon-like arrangement. Unlike other archaeal homologs, the putative biotin protein ligases (BPLs) of M. barkeri and the closely related euryarchaeon Archaeoglobus fulgidus appeared to be of the Escherichia coli-type (bifunctional, with two activities: BirA or a repressor of the biotin operon and BPL). We found the element Tyr(Phe)ProX(5)Phe(Tyr) to be fully conserved in biotin-dependent enzymes; it might function as the hinge for their "swinging arms."
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PMID:Oxaloacetate synthesis in the methanarchaeon Methanosarcina barkeri: pyruvate carboxylase genes and a putative Escherichia coli-type bifunctional biotin protein ligase gene (bpl/birA) exhibit a unique organization. 1137 47

Long-term caloric restriction (CR) has been shown to extend maximum life span in laboratory rodents. We investigated the activities of gluconeogenic and transaminase enzymes in the livers of old and young mice fed either control or calorie-restricted diets. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant increases in the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase when compared with controls, indicating increased gluconeogenesis. Increased activities of tyrosine, tryptophan, histidine, phenylalanine, alanine and aspartate transaminases, as well as of malate and glutamate dehydrogenases were also observed, while branched-chain amino acid transaminase was unchanged. Young mice on CR showed a significant increase only in the phosphoenolpyruvate carboxykinase activity in the gluconeogenic pathway, while transaminases were increased significantly, except for tryptophan and branched-chain amino acid transaminases. Glutamate dehydrogenase also showed increased activity but malate dehydrogenase was unchanged. Increases in the level of acetyl-CoA and [Acetyl-CoA]/[CoA] ratio were observed only in the old CR mice. Our results demonstrate increased gluconeogenic activity in CR mice and are consistent with a state of increased hepatic gluconeogenesis and protein turnover during CR.
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PMID:Caloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver. 1258 90