Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.4 (glutamate dehydrogenase)
 4,358 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The probable involvement of hepatic carbamyl-P in the reciprocal relationship between hepatic ureagenesis and glycogenesis from glucose was explored. Isolated perfused liver preparations from 48-h fasted rats were employed. Moderate (9.2 mM) and relatively high levels of glucose (34 mM) were perfused. Hepatic glycogenesis, glucose-6-P, carbamyl-P, and citrulline levels, hepatic urea formation, and ureagenesis based upon perfusate urea levels were measured. Experimental probes selected to modify hepatic ureagenesis and carbamyl-P production and utilization included: (a) NH4Cl, maintained at 5 mM by continuous infusion (NH4+ is a substrate for carbamyl-P synthase I and glutamate dehydrogenase); (b) norvaline, an inhibitor of ornithine transcarbamylase which catalyzes the first committed step in the urea cycle; and (c) ethoxyzolamide, an inhibitor of carbonic anhydrase which produces HCO3-, an essential substrate for carbamyl-P synthase I. NH4+ increased ureagenesis and decreased glycogenesis. The inclusion of norvaline with NH4+ decreased ureagenesis and increased glycogenesis. Ethoxyzolamide with or without NH4+ inhibited both ureagenesis and glycogenesis, and decreased the hepatic glucose-6-P level. Glycogenesis was greater at 34 mM than 9.2 mM glucose, increased in norvaline-containing preparations correlative with increased availability of carbamyl-P, and decreased when carbamyl-P formation was inhibited by ethoxyzolamide. Kinetic analysis indicated a Km, Glc of 31 mM for glucose phosphorylation preliminary to glycogenesis. Glycogen formation via the "indirect pathway" (i.e. involving extrahepatic glycolysis, transport of lactate to the liver, and glyconeogenesis therefrom) was quantitatively insufficient to account for the observed glycogenesis. Glucokinase is contraindicated by the inverse relationship between hepatic glycogenesis and ATP availability in the ethoxyzolamide-treated preparations. In contrast, carbamyl-P:glucose phosphotransferase activity of the glucose-6-phosphatase system has the characteristics to bridge hepatic ureagenesis and glycogenesis.
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PMID:Glycogenesis from glucose and ureagenesis in isolated perfused rat livers. Influence of ammonium ion, norvaline, and ethoxyzolamide. 813 5

Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM)). Mutations of beta cell ion channels involved in insulin secretion regulation also alter glucose sensing. Activating or inactivating mutations of ATP-dependent potassium (KATP ) channel genes result in severe but completely opposite clinical phenotypes, including PNDM and CHI. Mutations of the other ion channels, including voltage-gated potassium channels (Kv 7.1) and voltage-gated calcium channels, also lead to abnormal glucose sensing and CHI. Furthermore, amino acids can stimulate insulin secretion in a glucose-independent manner in some forms of CHI, including activating mutations of the glutamate dehydrogenase gene, HDAH deficiency, and inactivating mutations of KATP channel genes. These genetic defects have provided insight into a better understanding of the complicated nature of beta cell fuel-sensing mechanisms.
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PMID:Nutrient sensing in pancreatic islets: lessons from congenital hyperinsulinism and monogenic diabetes. 2904 8