Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When we incubated biotin carboxylase from Escherichia coli with ATP in absence of biotin we observed HCO3- -dependent ATP hydrolysis, which was activated by 10% ethanol in the same proportion as the activity of D-biotin carboxylation assayed in the presence of biotin. The two activities exhibited identical heat stability and were protected equally by glycerol; both required Mg2+ and K+ and showed similar dependency on the concentration of ATP. Biotin assay excluded potential contamination by traces of biotin as a cause of the observed ATP hydrolysis, and this was confirmed by the findings that carboxybiotin did not accumulate and that avidin was uninhibitory. Therefore we concluded that this HCO3- -dependent ATPase was genuinely a partial activity of biotin carboxylase. This partial activity supports a sequential mechanism for enzymatic carboxylation of biotin in which HCO3- is activated by ATP in a first step. It is consistent with the initial formation of the carbonic-phosphoric anhydride (HOCO2PO3(2-)), and it does not agree with models where biotin is phosphorylated by ATP prior to reaction with HCO3-. It appears that enzymes that use HCO3- for carboxylation, including biotin-dependent carboxylases, phosphoenolpyruvate carboxylase, and carbamoyl phosphate synthetase, activate HCO3- by a common mechanism involving the initial formation of the carbonic-phosphoric anhydride.
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PMID:ATPase activity of biotin carboxylase provides evidence for initial activation of HCO3- by ATP in the carboxylation of biotin. 294 46

Cell-free extracts of Bacillus licheniformis were found to contain pyruvate carboxylase which catalyzes the reaction between pyruvate and bicarbonate to yield oxalacetate in the presence of adenosine triphosphate (ATP), acetylcoenzyme A (CoA), and manganese. The plot between the reaction velocity of the carboxylation by the partially purified pyruvate carboxylase (25-fold) and the concentration of pyruvate, bicarbonate, manganese, and ATP did not indicate a pronounced deviation from the Michaelis-Menten hyperbola. The enzyme was inhibited by avidin and aspartate. Biotin partially protected the enzyme from avidin inhibition, whereas the amount of inhibition by aspartate was dependent on the concentration of acetyl-CoA present. The intracellular concentration of acetyl-CoA did not vary significantly enough to allow control of the enzyme by this method. Extracts of 4-hr postexponential-phase cells of B. licheniformis were also found to contain phosphoenolpyruvate carboxykinase, which appears to be under catabolite repression control. It is suggested that the endogenous induction of this enzyme is the determining factor allowing the shift to gluconeogenesis from glycolysis during sporulation of glucose-grown cells.
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PMID:Characterization and regulation of pyruvate carboxylase of Bacillus licheniformis. 505 52

Glucokinase (GK), expressed in hepatocyte and pancreatic beta cells, has a central regulatory role in glucose metabolism. Efficient GK activity is required for normal glucose-stimulated insulin secretion, postprandial hepatic glucose uptake, and the appropriate suppression of hepatic glucose output and gluconeogenesis by elevated plasma glucose. Hepatic GK activity is subnormal in diabetes, and GK may also be decreased in the beta cells of type II diabetics. In supraphysiological concentrations, biotin promotes the transcription and translation of the GK gene in hepatocytes; this effect appears to be mediated by activation of soluble guanylate cyclase. More recent evidence indicates that biotin likewise increases GK activity in islet cells. On the other hand, high-dose biotin suppresses hepatocyte transcription of phosphoenolpyruvate carboxykinase, the rate-limiting enzyme for gluconeogenesis. Administration of high-dose biotin has improved glycemic control in several diabetic animals models, and a recent Japanese clinical study concludes that biotin (3 mg t.i.d. orally) can substantially lower fasting glucose in type II diabetics, without side-effects. The recently demonstrated utility of chromium picolinate in type II diabetes appears to reflect improved peripheral insulin sensitivity--a parameter which is unlikely to be directly influenced by biotin. Thus, the joint administration of supranutritional doses of biotin and chromium picolinate is likely to combat insulin resistance, improve beta-cell function, enhance postprandial glucose uptake by both liver and skeletal muscle, and inhibit excessive hepatic glucose production. Conceivably, this safe, convenient, nutritional regimen will constitute a definitive therapy for many type II diabetics, and may likewise be useful in the prevention and management of gestational diabetes. Biotin should also aid glycemic control in type I patients.
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PMID:High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes. 1041 47

Biotin causes improvements in disordered glucose metabolism by stimulating glucose-induced insulin secretion in pancreatic beta-cells and by accelerating glycolysis in liver and pancreas. Biotin is known to regulate hepatic and pancreatic glucokinase expression at both transcriptional and translational levels, and to regulate hepatic phosphoenolpyruvate carboxykinase expression at the transcriptional level. The effects of biotin on glucose-induced insulin secretion were investigated using the method of isolated pancreas perfusion. The pancreas of the biotin-deficient rat has an impaired insulin response to both glucose and arginine. In control rats as well as biotin-deficient rats, the insulin response to glucose stimulation was enhanced by the addition of 1 mM biotin to the perfusate. Biotin-induced enhancement of glucose-induced insulin release was evident within the first few minutes of perfusion. Since any effects on the glucokinase synthesis pathway would not be seen for at least 30 minutes, these results indicate that biotin may have the ability to act directly on the insulin secreting function of pancreatic beta-cells. Biotin perfusion was not found to cause enhancement of the arginine-induced insulin response, suggesting that biotin has no significant effects on the distal portion of the signaling pathway involved in insulin secretion. These results indicate that the administration of a high concentrations of biotin may improve the metabolism and/or utilization of glucose in patients with non-insulin-dependent diabetes mellitus.
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PMID:[Enhancement of glucose-induced insulin secretion and modification of glucose metabolism by biotin]. 1054 Aug 72

The role of biotin as the prosthetic group of the four biotin-dependent carboxylases in higher organisms is well recognized. Based on the roles of these carboxylases in metabolism, the requirement of biotin for cell viability, growth and differentiation was established. Biotin seems to have a role in cell functions other than as the prosthetic group of biotin enzymes. Biotin seems to influence processes such as the proliferation of the mesenchyme, spermatogenesis and song-bird vocalization. A direct effect of biotin, at the transcriptional level, has been shown for the key enzymes of glucose metabolism. Glucokinase, a key glycolytic enzyme, and phosphoenolpyruvate carboxykinase (PEPCK), a key gluconeogenic enzyme, are regulated in opposite directions by biotin in a manner similar to the action of insulin.
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PMID:Biotin--a regulator of gene expression. 1599 82

In the last few decades, more vitamin-mediated effects have been discovered at the level of gene expression. Increasing knowledge on the molecular mechanisms of these vitamins has opened new perspectives that form a connection between nutritional signals and the development of new therapeutic agents. Besides its role as a carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism: Biotin has stimulatory effects on genes whose action favors hypoglycemia (insulin, insulin receptor, pancreatic and hepatic glucokinase); on the contrary, biotin decreases the expression of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme that stimulates glucose production by the liver. The findings that biotin regulates the expression of genes that are critical in the regulation of intermediary metabolism are in agreement with several observations that indicate that biotin supply is involved in glucose and lipid homeostasis. Biotin deficiency has been linked to impaired glucose tolerance and decreased utilization of glucose. On the other hand, the diabetic state appears to be ameliorated by pharmacological doses of biotin. Likewise, pharmacological doses of biotin appear to decrease plasma lipid concentrations and modify lipid metabolism. The effects of biotin on carbohydrate metabolism and the lack of toxic effects of the vitamin at pharmacological doses suggest that biotin could be used in the development of new therapeutics in the treatment of hyperglycemia and hyperlipidemia, an area that we are actively investigating.
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PMID:Pharmacological effects of biotin. 1599 83

Biotin functions as a coenzyme for four carboxylases involved in energy metabolism in mammals. Besides these classical functions, biotin has novel functions in the cellular processes via the modulation of gene expression. In this study, we examined the alteration of gene expression by biotin administration in the liver of streptozotocin (STZ)-induced diabetic rats. In comparison with the control, the mRNA levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were significantly reduced and glucokinase mRNA was increased 3 h after the administration of biotin or insulin. The expression of hepatocyte nuclear factor 4alpha, one of the transcription factors responsible for gluconeogenic gene expression, was decreased by biotin at both mRNA and protein levels. In addition, forkhead box O1 and sterol regulatory element-binding protein 1c mRNA expression that was enhanced by the insulin treatment was inversely decreased by biotin. These results indicate that biotin repressed the gluconeogenic genes and their transcription factors via a pathway independent of insulin-signaling and could improve the diabetic condition.
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PMID:Effect of biotin treatment on hepatic gene expression in streptozotocin-induced diabetic rats. 1846 Aug 17