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Pyruvate dehydrogenase kinase

About: Pyruvate dehydrogenase kinase is a research topic. Over the lifetime, 4224 publications have been published within this topic receiving 161052 citations. The topic is also known as: [pyruvate dehydrogenase (lipoamide)] kinase & pyruvate dehydrogenase (lipoamide) kinase.


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Journal ArticleDOI
TL;DR: The experimental results indicate that the reaction mechanism is equilibrium random-order in type, that the substrates and products are phosphoenolpyruvate, ADP, Mg(2+), pyruVate and MgATP, and that dead-end complexes, between pyruvates,ADP and M g(2+) form randomly and exist in equilibrium with themselves and other substrate complexes.
Abstract: The paper reports a study of the kinetics of the reaction between phosphoenolpyruvate, ADP and Mg(2+) catalysed by rabbit muscle pyruvate kinase. The experimental results indicate that the reaction mechanism is equilibrium random-order in type, that the substrates and products are phosphoenolpyruvate, ADP, Mg(2+), pyruvate and MgATP, and that dead-end complexes, between pyruvate, ADP and Mg(2+), form randomly and exist in equilibrium with themselves and other substrate complexes. Values were determined for the Michaelis, dissociation and inhibition constants of the reaction and are compared with values ascertained by previous workers.

79 citations

Journal ArticleDOI
TL;DR: This review uses information derived from calcium binding studies, analysis of conserved calcium binding motifs and comparison of amino acid sequences from calcium sensitive and non-sensitive enzymes to discuss how the recent cloning of several subunits from the four dehydrogenases enhances the authors' understanding of the ways in which these enzymes bind calcium.
Abstract: In mammalian cells, increases in calcium concentration cause increases in oxidative phosphorylation. This effect is mediated by the activation of four mitochondrial dehydrogenases by calcium ions; FAD-glycerol 3-phosphate dehydrogenase, pyruvate dehydrogenase, NAD-isocitrate dehydrogenase and oxoglutarate dehydrogenase. FAD-glycerol 3-phosphate dehydrogenase, being located on the outer surface of the inner mitochondrial membrane, is exposed to fluctuations in cytoplasmic calcium concentration. The other three enzymes are located within the mitochondrial matrix. While the kinetic properties of all of these enzymes are well characterised, the molecular basis for their regulation by calcium is not. This review uses information derived from calcium binding studies, analysis of conserved calcium binding motifs and comparison of amino acid sequences from calcium sensitive and non-sensitive enzymes to discuss how the recent cloning of several subunits from the four dehydrogenases enhances our understanding of the ways in which these enzymes bind calcium. FAD-glycerol 3-phosphate dehydrogenase binds calcium ions through a domain which is part of the polypeptide chain of the enzyme. In contrast, it is possible that the calcium sensitivity of the other three dehydrogenases may involve separate calcium binding subunits.

79 citations

Journal ArticleDOI
TL;DR: The results suggest that Ala-398 is one of the most critical residues allowing the enzyme to prefer the R-state and that allosteric regulation of pyruvate kinase involves amino acid residues in the intersubunit contact.

79 citations

Journal ArticleDOI
TL;DR: It is concluded that pyruvate dehydrogenase is the rate-limiting step during pyruviate oxidation in the presence of malate, and that in human skeletal muscle mitochondria pyruVate oxidation proceeds maximally both in the absence of malates or carnitine.

79 citations

Journal ArticleDOI
TL;DR: The role of fatty acids in the regulation of kidney cortex pyruvate metabolism is confirmed and the results are compared with previously published observations on theregulation of pyruVate dehydrogenase in vivo and confirmed.
Abstract: Pyruvate dehydrogenase activity was measured in extracts of isolated kidney cortex tubules, prepared by collagenase treatment. The measured activities were comparable to those described previously for whole kidney homogenates. Incubation of tubules in vitro in the absence of exogenous substrates led to a steady increase in enzyme activity over 30 min. This increase was not significantly changed by the addition of several gluconeogenic substrates including lactate, glutamine, glutamate, glycerol, fructose and malate. 1 mM oleate, 5 mM acetate and 20 mM 2-oxoglutarate however, prevented this increase completely. In contrast, glucose and dihydroxyacetone accelerated the activation of pyruvate dehydrogenase during incubation in vitro. 20 mM pyruvate very rapidly activated pyruvate dehydrogenase with a following decrease below the activity of control experiments without substrate. 1 mM oleate and 20 mM 2-oxoglutarate counteracted the increase in pyruvate dehydrogenase activity caused by glucose and dihydroxyacetone and had no effect in the presence of 20 mM pyruvate. Determination of the inactive part of pyruvate dehydrogenase after addition of purified pyruvate dehydrogenase phosphatase revealed that all changes observed were probably caused by enzymatic interconversion of pyruvate dehydrogenase. The results are compared with previously published observations on the regulation of pyruvate dehydrogenase in vivo and confirm the role of fatty acids in the regulation of kidney cortex pyruvate metabolism.

79 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202329
202234
202161
202063
201959
201851