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

Activities (mumol X min-1 X g liver) and zonal distributions of key enzymes of carbohydrate metabolism were studied in livers of streptozotocin-diabetic rats and compared to the values in alloxan-diabetes. Streptozotocin led to a non-ketotic diabetes with blood glucose being increased by more than fivefold but ketone bodies being in the normal range, while alloxan produced a ketotic diabetes with blood glucose, acetoacetate and beta-hydroxybutyrate being elevated by more than fivefold. Portal insulin was decreased to about 20% in streptozotocin- and more drastically to about 7% in alloxan-diabetes. Conversely, portal glucagon was increased in the two states to about 250% and 180%, respectively. The glucogenic key enzyme phosphoenolpyruvate carboxykinase (PEPCK) was enhanced in streptozotocin- and alloxan-diabetes to over 300%, while the glycolytic pyruvate kinase L (PKL) was lowered to 65% and 80%, respectively. The normal periportal to perivenous gradient of PEPCK of about 3:1, as measured in microdissected tissue samples, was maintained with elevated activities in the two zones. The normal periportal to perivenous gradient of PKL of 1:1.7 was diminished with lowered activities in the two zones. The glucogenic glucose-6-phosphatase (G6Pase) was increased in streptozotocin- and alloxan-diabetes to 130% and 140%, respectively, while the glucose utilizing glucokinase (GK) was decreased to 60% and 50%, respectively. The normal periportal to perivenous gradient of G6Pase, demonstrated histochemically, remained unaffected. Carnitine palmitoyltransferase (CPT) was increased to over 190% and acetyl-CoA carboxylase (ACC) was decreased to 60% in streptozotocin, non-ketotic diabetes, while the two enzymes were altered more drastically to 400% and 50%, respectively, in alloxan, ketotic diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gluconeogenic-glycolytic capacities and metabolic zonation in liver of rats with streptozotocin, non-ketotic as compared to alloxan, ketotic diabetes. 302 62

A quantitative study of the effect of carnitine deficiency on expression of glycolytic and gluconeogenic enzymes was performed using juvenile visceral steatosis mice which are systemically deficient in carnitine. The amounts of glucokinase and L-type pyruvate kinase mRNA were reduced in homozygotes, compared to heterozygotes and normal controls at 2 and 8 weeks. Liver-type phosphofructokinase, however, did not differ significantly. The abundance of fructose 1,6-bisphosphatase mRNA was unchanged at 2 and 8 weeks. The level of phosphoenolpyruvate carboxykinase mRNA was increased slightly at 2 weeks, but not at 8 weeks. A part of these changes could not be explained by the plasma glucose or insulin level. Carnitine administration restored the mRNA of these enzymes to normal levels. These results suggest that carnitine deficiency affects the expression of these liver enzymes.
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PMID:Disordered expression of glycolytic and gluconeogenic liver enzymes of juvenile visceral steatosis mice with systemic carnitine deficiency. 885 99

Hyperammonemia is one of the major symptoms of primary carnitine deficiency. Carnitine-deficient juvenile visceral steatosis (JVS) mice show hyperammonemia during the weaning period. We have found that all of the urea cycle enzyme genes are suppressed and that N-acetylglutamate, an allosteric activator of the first step enzyme of the urea cycle, carbamoyl phosphate synthetase I (CPS), is not deficient in the liver of JVS mice. Induction of the urea cycle enzymes by glucocorticoid in rat primary cultured hepatocytes was suppressed by the addition of long-chain fatty acids. The suppression of the urea cycle enzyme genes in vivo and in vitro is accompanied by stimulated AP-1 DNA-binding activity. However, mRNA of phosphoenolpyruvate carboxykinase, one of the gluconeogenic enzymes which responds to glucocorticoid, is further stimulated by the addition of fatty acid. From these results, we postulate that protein-protein interaction between glucocorticoid receptors and AP-1 is not the major mechanism of suppression, but that AP-1 causes the suppression through a cis-element on the gene. After cloning promoter and enhancer regions of the mouse CPS gene and comparing rat and mouse, we found that an AP-1 site was present just 3'-downstream of the minimal essential enhancer fragment previously described. We also found that the presence of an AP-1 site in reporter gene constructs resulted in suppression of the reporter genes in the liver of carnitine-deficient JVS mice and suppression of glucocorticoid induction by long-chain fatty acid in cultured hepatocytes.
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PMID:Antagonizing effect of AP-1 on glucocorticoid induction of urea cycle enzymes: a study of hyperammonemia in carnitine-deficient, juvenile visceral steatosis mice. 1113 45