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)

The liver is the "glucostat" of the organism and serves at the same time as an "ammonia-sink and pH stat". The key enzymes involved in glucose uptake and release and in urea and glutamine formation are reciprocally distributed over the liver parenchyma: The glucogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK), fructosebisphosphatase (FBPase) and glucose-6-phosphatase (G6Pase) as well as the ureagenic enzyme carbamoylphosphate synthetase (CAPS) are predominant in the periportal zone. The glycolytic enzymes glucokinase (GK) and pyruvate kinase type L (PKL) as well as the glutaminogenic enzyme glutamine synthetase (GluNS) are prevalent in the perivenous zone. This heterogeneity appears to be a prerequisite for the normal "glucostat, ammonia-sink and pH-stat" function of the liver. After birth the liver is a gluconeogenic organ, only with weaning it becomes a "glycolytic/gluconeogenic" glucostat. In the rat zonation of PEPCK, G6Pase and CAPS developed gradually after birth and was completed before weaning, i.e. before it would be functionally required. After 2/3 partial hepatectomy the liver looses its normal glucostat function and becomes a gluconeogenic organ. With this change the zonation of PEPCK and PKL were also lost; it was restored only during the second week after operation. During starvation the liver also looses its glucostat function to become the major glucose supplier of the organism. Zonation of PEPCK and PKL were diminished to such an extent that the major function of the perivenous zone was altered from glucose uptake to release. In diabetes the liver does not loose its glucostat function; however, the function is severely impaired. Zonation of PEPCK was increased and that of PKL decreased in such a manner that the major function of the perivenous zone, glucose uptake, was not entirely changed but only diminished. It can be concluded that in the various physiological states studied the zonation of enzymes correlated well with the glucostat function of the liver.
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PMID:Dynamics of zonal hepatocyte heterogeneity. Perinatal development and adaptive alterations during regeneration after partial hepatectomy, starvation and diabetes. 301 Mar 76

Estradiol treatment of starving immature rainbow trout dramatically alters the metabolic performance of isolated hepatocytes. One and two weeks postimplantation with estradiol, the rate of de novo glucose synthesis from [14C]alanine is reduced fourfold from 0.4 mumol/g/hr to 0.1 mumol/g/hr, compared with vehicle-injected control fish. After 6 weeks, the rate of glucose production on a gram wet weight basis is identical in both treatment groups, but significantly larger (by 80%) in the estradiol-treated group than in the controls, if expressed normalized to the hepatosomatic index (HSI). Estradiol treatment caused preferential partitioning of alanine carbon into oxidative pathways away from gluconeogenesis, indicated by a significantly lower ratio of glucose production over CO2 production in hepatocytes isolated from estradiol-treated animals. Incorporation of [14C]alanine into acid-precipitable protein is significantly larger in the estradiol-treated group after 2 weeks, and also after 6 weeks, when normalized to the HSI, indicating that part of the protein synthesized in the estradiol-treated groups is vitellogenin. No differences were detected between estradiol-treated animals and control animals in the activities of enzymes associated with gluconeogenesis [phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase (FBPase)] and amino acid metabolism (alanine and aspartate aminotransferases) in the time course investigated (expressed on a wet weight basis). Activities normalized to the HSI are higher in fish implanted with estradiol compared with controls at 2 and 6 weeks. In keeping with the increased potential of hepatocytes for CO2 production from alanine, estradiol treatment doubled and tripled the maximum activity of pyruvate kinase 1 and 2 weeks postimplantation, respectively. Fish were fasted to avoid erratic feeding due to treatments. Superimposed on estradiol actions are effects of starvation: a fourfold increase in the rate of gluconeogenesis, a threefold increase in oxidative flux, and a fivefold increase in the activity of FBPase--all normalized to hepatocyte weight.
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PMID:Gluconeogenesis in hepatocytes of immature rainbow trout (Oncorhynchus mykiss): control by estradiol. 767 84

The Wistar fatty rat is a model of obese non-insulin-dependent diabetes mellitus. Males, but not females, develop hyperglycemia, glucouria and polyuria within 8 weeks of age. The regulation of gene expression by insulin has been shown to be differentially impaired in the liver of the fatty rats. The genes resistant to insulin include glucokinase gene and phosphoenolpyruvate carboxykinase gene. In contrast, L-type pyruvate kinase gene responds to insulin normally, raising the possibility that the signaling pathway from the insulin receptor to the insulin-resistant genes, but not to the insulin-sensitive genes, is defective at a point beyond the receptor kinase in the fatty rats. On the other hand, female fatty rats develop hyperglycemia only when they are given sucrose for several weeks. This treatment causes a decrease in gucokinase while enzymes involved in gluconeogenesis are increased. Chronic feeding of sucrose also leads to hypertriglycemia and visceral fat accumulation, which is more frequently associated with abnormalities in glucose and lipid metabolisms. Fructose is believed to be the responsible component of sucrose for these effects. Hypertriglyceridemic effect of fructose is mainly due to an increase in hepatic production of VLDL. Most enzymes related to lipogenesis in the liver are induced by dietary fructose even in diabetes. L-type pyruvate kinase is one of such enzymes. Cis-acting element named PKL-III in the 5'-flanking region of this gene is shown to be responsive to dietary fructose as well as to dietary glucose. Thus, identification and characterization of a protein bound to this element could help in the further understanding of the molecular mechanism of the fructose actions.
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PMID:Insulin resistance in obesity and its molecular control. 858 76