Topic
Glycolysis
About: Glycolysis is a research topic. Over the lifetime, 10593 publications have been published within this topic receiving 507460 citations. The topic is also known as: GO:0006096 & glycolysis.
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TL;DR: The results show that in the intact liver, the oxidation of long-chain but not short-chain fatty acids proceeds almost entirely through carnitine-dependent pathways, and that the effect of fatty acids on gluconeogenesis is determined by their rate of oxidation and not by their concentration in the perfusion fluid.
Abstract: Oleic acid produced a two- to three-fold stimulation of glucose production from lactate in perfused livers from fasted rats. This effect was completely blocked by (+)-decanoylcarnitine, a known inhibitor of (−)-carnitine palmityltransferase. Activation of fatty acids to the acyl CoA esters was not inhibited. Neither β-oxidation of octanoate, nor its stimulatory effect on gluconeogenesis was blocked by (+)-decanoylcarnitine. The results show that in the intact liver, the oxidation of long-chain but not short-chain fatty acids proceeds almost entirely through carnitine-dependent pathways. Changes in the tissue levels of metabolic intermediates after addition of oleic acid show that the increased rate of gluconeogenesis was caused by a stimulation of the pyruvate carboxylase step. Attendant increases in the levels of acetyl CoA and NADH are consistent with the proposal that the mitochondrial levels of these intermediates control carbohydrate metabolism by diverting pyruvate from oxidation towards the synthesis of glucose. A further control site was identified upon fatty acid addition in the region of the phosphofructokinase and fructose diphosphatase reactions. There was no evidence for control at either of these steps by adenine nucleotides, but a marked rise of citrate was consistent with a postulated inhibition of phosphofructokinase. All the changes in the levels of intermediates of the gluconeogenic pathway and citric acid cycle induced by oleic acid were blocked by (+)-decanoylcarnitine. The failure of oleic acid to increase acetyl CoA and citrate levels in the presence of (+)-decanoylcarnitine explains its failure to stimulate gluconeogenesis under these conditions. It is concluded that the effect of fatty acids on gluconeogenesis is determined by their rate of oxidation and not by their concentration in the perfusion fluid. The significance of these findings in relation to the interactions of carbohydrate and fatty acid metabolism in vivo in the normal, starved and diabetic states is discussed.
137 citations
TL;DR: This study is the first to demonstrate an important role of amino acids in combination with insulin in the molecular regulation of hepatic metabolism.
Abstract: Amino acids are considered to be regulators of metabolism in several species, and increasing importance has been accorded to the role of amino acids as signalling molecules regulating protein synthesis through the activation of the TOR transduction pathway. Using rainbow trout hepatocytes, we examined the ability of amino acids to regulate hepatic metabolism-related gene expression either alone or together with insulin, and the possible involvement of TOR. We demonstrated that amino acids alone regulate expression of several genes, including glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, pyruvate kinase, 6-phospho-fructo-1-kinase and serine dehydratase, through an unknown molecular pathway that is independent of TOR activation. When insulin and amino acids were added together, a different pattern of regulation was observed that depended upon activation of the TOR pathway. This pattern included a dramatic up-regulation of lipogenic (fatty acid synthase, ATP-citrate lyase and sterol responsive element binding protein 1) and glycolytic (glucokinase, 6-phospho-fructo-1-kinase and pyruvate kinase) genes in a TOR-dependent manner. Regarding gluconeogenesis genes, only glucose-6-phosphatase was inhibited in a TOR-dependent manner by combination of insulin and amino acids and not by amino acids alone. This study is the first to demonstrate an important role of amino acids in combination with insulin in the molecular regulation of hepatic metabolism.
137 citations
TL;DR: During low-flow ischemia simulating an acute myocardial infarction region, oxidative phosphorylation accounted for 90% of ATP synthesis and the CK velocity fell, and CK did not completely use available PCr to slow ATP depletion, support the clinical use of G+I in acute MI.
Abstract: Background—Our goals were to (1) simulate the degree of low-flow ischemia and mixed anaerobic and aerobic metabolism of an acutely infarcting region; (2) define changes in anaerobic glycolysis, oxidative phosphorylation, and the creatine kinase (CK) reaction velocity; and (3) determine whether and how increased glycolytic substrate alters the energetic profile, function, and recovery of the ischemic myocardium in the isolated blood-perfused rat heart. Methods and Results—Hearts had 60 minutes of low-flow ischemia (10% of baseline coronary flow) and 30 minutes of reperfusion with either control or high glucose and insulin (G+I) as substrate. In controls, during ischemia, rate-pressure product and oxygen consumption decreased by 84%. CK velocity decreased by 64%; ATP and phosphocreatine (PCr) concentrations decreased by 51% and 63%, respectively; inorganic phosphate (Pi) concentration increased by 300%; and free [ADP] did not increase. During ischemia, relative to controls, the G+I group had similar CK velo...
137 citations
TL;DR: It is hypothesized that the growth defect of tpi1-null mutants is caused by mitochondrial reoxidation of cytosolic NADH, thus rendering it unavailable for dihydroxyacetone-phosphate reduction, and a quadruple mutant was constructed, which grew on glucose as the sole carbon source.
Abstract: Inactivation of TPI1, the Saccharomyces cerevisiae structural gene encoding triose phosphate isomerase, completely eliminates growth on glucose as the sole carbon source. In tpi1-null mutants, intracellular accumulation of dihydroxyacetone phosphate might be prevented if the cytosolic NADH generated in glycolysis by glyceraldehyde-3-phosphate dehydrogenase were quantitatively used to reduce dihydroxyacetone phosphate to glycerol. We hypothesize that the growth defect of tpi1-null mutants is caused by mitochondrial reoxidation of cytosolic NADH, thus rendering it unavailable for dihydroxyacetone-phosphate reduction. To test this hypothesis, a tpi1delta nde1delta nde2delta gut2delta quadruple mutant was constructed. NDE1 and NDE2 encode isoenzymes of mitochondrial external NADH dehydrogenase; GUT2 encodes a key enzyme of the glycerol-3-phosphate shuttle. It has recently been demonstrated that these two systems are primarily responsible for mitochondrial oxidation of cytosolic NADH in S. cerevisiae. Consistent with the hypothesis, the quadruple mutant grew on glucose as the sole carbon source. The growth on glucose, which was accompanied by glycerol production, was inhibited at high-glucose concentrations. This inhibition was attributed to glucose repression of respiratory enzymes as, in the quadruple mutant, respiratory pyruvate dissimilation is essential for ATP synthesis and growth. Serial transfer of the quadruple mutant on high-glucose media yielded a spontaneous mutant with much higher specific growth rates in high-glucose media (up to 0.10 h(-1) at 100 g of glucose. liter(-1)). In aerated batch cultures grown on 400 g of glucose. liter(-1), this engineered S. cerevisiae strain produced over 200 g of glycerol. liter(-1), corresponding to a molar yield of glycerol on glucose close to unity.
137 citations
TL;DR: It is concluded that epinephrine may override many of the actions of insulin in vivo, and most of these effects are mediated via the beta-adrenergic receptor.
137 citations