Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aluminum, an abundant element in the earth's crust, has been implicated in various pathological disorders and low concentrations of this element have recently been shown to inhibit brain glycolysis. However, despite the fact that aluminum accumulates in high concentrations in the liver, potential effects of this metal on hepatic intermediary metabolism have not been explored. In perfused livers from untreated rats, maximal rates of production of lactate plus pyruvate (glycolysis) were 93 +/- 15 mumols/g/hr. Glycolysis was severely inhibited in livers from aluminum-treated rats (0.5 mg/kg, 6 hr before experiment) with maximal rates of only 23 +/- 4 mumols/g/hr. In contrast, glucose production (glycogenolysis) and hepatic oxygen uptake were not altered significantly by prior treatment with aluminum. In livers from fasted rats, pretreatment with aluminum did not influence gluconeogenesis or production of lactate and pyruvate from fructose (5 mM). This finding indicates that pyruvate kinase is not inhibited by aluminum and implicates phosphofructokinase, hexokinase and/or glucokinase as sites for the inhibitory effect of aluminum on glycolysis. In liver homogenates from untreated rats, increasing concentrations of aluminum did not show any appreciable effect on hexokinase or glucokinase activity but did cause progressive decreases in phosphofructokinase activity. Therefore, aluminum-induced inhibition of liver phosphofructokinase, an important control site in the glycolytic pathway, is most likely responsible for aluminum-induced inhibition of hepatic glycolysis.
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PMID:Mechanism of aluminum-induced inhibition of hepatic glycolysis: inactivation of phosphofructokinase. 214 21

1. The time-course for the induction of hepatic glucokinase, hexokinase, phosphofructokinase, liver-type and muscle-type pyruvate kinases in reponse to various diets and insulin has been investigated over the first 48h of change in both diabetic and non-diabetic rats. 2. The results are consistent with there being separate regulatory mechanisms for the induction of each of the three key enzymes, that is for glucokinase, phosphofructokinase and liver-type pyruvate kinase. 3. To investigate the possibility that induction of these enzymes is mediated through specific metabolites a full metabolite profile has been determined under conditions identical with those in the induction experiments and the results examined for correlations between metabolite concentrations and enzyme activities. 4. Several such relationships were detected and those between glucokinase activity and the phosphorylation state of the adenine nucleotides and between liver-type pyruvate kinase activity and the concentrations of dihydroxyacetone phosphate and pyruvate are discussed in relation to the concept of inducing metabolites. 5. It is suggested that the induction of glycolytic enzymes by insulin may be secondary to the changes in the concentration of specific hepatic metabolites brought about by the acute effects of the hormone. 6. The details of the metabolite concentrations in the various experimental states have been deposited as Supplementary Publication SUP 50021 at the British Library (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973), 131, 5.
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PMID:Relationships between concentration of hepatic intermediary metabolites and induction of the key glycolytic enzymes in vivo. 427 55