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)

Glycerol, glycerol-3-phosphate (G3P), and dihydroxyacetone phosphate (DHAP) were evaluated as inhibitors of gluconeogenesis on rat liver enzymes in vitro, and for their effects on glucose formation in vivo in well-nourished and malnourished rats. DHAP was more potent as an inhibitor than G3P on fructose-1,6-diphosphatase (FDPase), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase). The I50 for DHAP was 2, 8, and 9 x 10(-3) M, respectively. No effect was observed on rat liver pyruvate carboxylase (PC). Glycerol was a weak inhibitor of FDPase and PEPCK, but did not inhibit PC and G6Pase. In vivo, when G3P was injected before a parenteral L-alanine (Ala) challenge, it produced a hypoglycemic effect in malnourished rats and a lesser, but noticeable, blood glucose level reduction in well-fed animals. Glycerol caused a smaller reduction in glucose formation from Ala. No comparable effects were observed after a fructose pretreatment. These results underscore the potential hypoglycemic effects of phosphorylated glycerol metabolites and identify the steps in gluconeogenesis where this action is exerted. The study also stresses the nutritional component in the glycerol intolerance syndrome, apparent from the far more severe effects observed in malnourished rats given G3P or glycerol prior to Ala.
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PMID:Regulation of gluconeogenesis by glycerol and its phosphorylated derivatives. 298 19

Glycerol has become an ideal feedstock for the microbial production of bio-based chemicals due to its abundance, low cost, and high degree of reduction. We have previously reported the pathways and mechanisms for the utilization of glycerol by Escherichia coli in minimal salts medium under microaerobic conditions. Here we capitalize on such results to engineer E. coli for the production of value-added succinate from glycerol. Through metabolic engineering of E. coli metabolism, succinate production was greatly elevated by (1) blocking pathways for the synthesis of competing by-products lactate, ethanol, and acetate and (2) expressing Lactococcus lactis pyruvate carboxylase to drive the generation of succinate from the pyruvate node (as opposed to that of phosphoenolpyruvate). As such, these metabolic engineering strategies coupled cell growth to succinate production because the synthesis of succinate remained as the primary route of NAD+ regeneration. This feature enabled the operation of the succinate pathway in the absence of selective pressure (e.g. antibiotics). Our biocatalysts demonstrated a maximum specific productivity of approximately 400 mg succinate/g cell/h and a yield of 0.69 g succinate/g glycerol, on par with the use of glucose as a feedstock.
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PMID:Metabolic engineering of Escherichia coli for the production of succinate from glycerol. 2060 Oct 68

Nutritional status and glucose precursors are known regulators of gluconeogenic gene expression. Glycerol can replace corn in diets fed to dairy cows and use of glycerol is linked to increased rumen propionate production. The effect of dietary glycerol on the regulation of gluconeogenic enzymes is unknown. The objective of this study was to examine the effect of glycerol on expression of pyruvate carboxylase (PC), cytosolic and mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-C and PEPCK-M), and glucose-6-phosphatase. Twenty-six multiparous Holstein cows were fed either a control diet or a diet where high-moisture corn was replaced by glycerol from -28 through +56 d relative to calving (DRTC). Liver tissue was collected via percutaneous liver biopsy at -28, -14, +1, +14, +28, and +56 DRTC for RNA analysis. Expression of PC mRNA increased 6-fold at +1 and 4-fold at +14 DRTC relative to precalving levels. Dietary glycerol did not alter expression of PC mRNA expression. Expression of PEPCK-C increased 2.5-fold at +14 and 3-fold at +28 DRTC compared with +1 DRTC. Overall, dietary glycerol increased PEPCK-C expression compared with that of cows fed control diets. The ratio of PC to PEPCK-C was increased 6.3-fold at +1 DRTC compared with precalving and tended to be decreased in cows fed glycerol. We detected no effect of diet or DRTC on PEPCK-M or glucose-6-phosphatase mRNA, and there were no interactions of dietary treatment and DRTC for any transcript measured. Substituting corn with glycerol increased the expression of PEPCK-C mRNA during transition to lactation and suggests that dietary energy source alters hepatic expression. The observed increase in PEPCK-C expression with glycerol feeding may indicate regulation of hepatic gene expression by changes in rumen propionate production.
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PMID:Short communication: Regulation of hepatic gluconeogenic enzymes by dietary glycerol in transition dairy cows. 2654 49

Glycerol is a major by-product of the biodiesel industry. In this study we report on the metabolic networks involved in its transformation into pyruvate, phosphoenolpyruvate (PEP) and ATP. When the nutritionally-versatile Pseudomonas fluorescens was exposed to hydrogen peroxide (H2O2) in a mineral medium with glycerol as the sole carbon source, the microbe reconfigured its metabolism to generate adenosine triphosphate (ATP) primarily via substrate-level phosphorylation (SLP). This alternative ATP-producing stratagem resulted in the synthesis of copious amounts of PEP and pyruvate. The production of these metabolites was mediated via the enhanced activities of such enzymes as pyruvate carboxylase (PC) and phosphoenolpyruvate carboxylase (PEPC). The high energy PEP was subsequently converted into ATP with the aid of pyruvate phosphate dikinase (PPDK), phosphoenolpyruvate synthase (PEPS) and pyruvate kinase (PK) with the concomitant formation of pyruvate. The participation of the phospho-transfer enzymes like adenylate kinase (AK) and acetate kinase (ACK) ensured the efficiency of this O2-independent energy-generating machinery. The increased activity of glycerol dehydrogenase (GDH) in the stressed bacteria provided the necessary precursors to fuel this process. This H2O2-induced anaerobic life-style fortuitously evokes metabolic networks to an effective pathway that can be harnessed into the synthesis of ATP, PEP and pyruvate. The bioconversion of glycerol to pyruvate will offer interesting economic benefit.
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PMID:Metabolic networks to generate pyruvate, PEP and ATP from glycerol in Pseudomonas fluorescens. 2692 Apr 81

Flux Balance Analysis was performed for Clostridium sporogenes NCIM 2918 grown on sole glucose and glycerol or glucose-glycerol combinations at varied concentrations. During acidogenesis, glucose and glucose-glycerol combinations favored improved growth and butyric acid production. Glycerol fermentation was however marked by reduced growth and predominant ethanol synthesis. Further, with increase of glycerol fraction in glucose-glycerol blend, flux towards ethanol synthesis linearly increased with simultaneous decrease in butanol flux. Elevated ATP demand due to improved growth was satisfied by upregulated carbon flux towards butyric acid synthesis during both glucose and dual substrate fermentations. Possible repression of pyruvate carboxylase by glycerol resulting in downturn of carbon uptake flux towards TCA cycle through anaplerotic reaction may be responsible for reduced growth in glycerol fermentation. Ammonium acetate mediated induction of acetic acid utilization, during acidogenesis, led to excess acetyl-CoA generation and its subsequent metabolism to lesser reduced products, butyric acid or ethanol.
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PMID:Understanding regulation in substrate dependent modulation of growth and production of alcohols in Clostridium sporogenes NCIM 2918 through metabolic network reconstruction and flux balance analysis. 2913 31