3-oxo acid coenzyme A-transferase in normal and diabetic rat muscle

Fenselau, Allan; Wallis, Kathleen

doi:10.1042/bj1580509

Cited by 16 publications

(9 citation statements)

References 17 publications

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“…A similar reaction mechanism has been proposed for a purified pig heart enzyme (Hersh and Jencks, 1967) and a partially purified rat brain enzyme (Tildon and Sevdalian, 1972). Another characteristic of this type of kinetic mechanism is inhibition by high substrate concentrations (Hersh and Jencks, 1967;Fenselau and Wallis, 1976). A Hill plot of our data (Fig.…”

Section: J J Russell a N D M S P A L E Lsupporting

confidence: 82%

Purification and Properties of Succinyl‐CoA:3‐Oxo‐Acid CoA‐Transferase from Rat Brain

Russell

Patel

1982

Journal of Neurochemistry

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Rat brain succinyl-CoA:3-oxo-acid CoA-transferase (3-oxo-acid CoA-transferase, EC 2.8.3.5), the first committed enzyme in the oxidation of ketone bodies in mitochondria, was purified to apparent homogeneity as judged by polyacrylamide gel electrophoresis. The enzyme has an apparent molecular weight of 90,000 as determined by G-150 Sephadex chromatography, and an apparent subunit molecular weight of 53,000 as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The specific activity of the purified enzyme was approximately 161 mumol/min/mg of protein. Initial velocity studies of the forward reaction (acetoacetate leads to acetoacetyl-CoA) are consistent with a "ping pong" mechanism. Substrate inhibition appears above approximately 1 mM acetoacetate. Apparent Km values were 70 microM for acetoacetate and 156 microM for succinyl-CoA (the forward reaction), and 59 microM for acetoacetyl-CoA and 25 mM for succinate (the reverse reaction). These values are markedly different from those reported for this enzyme from pig heart.

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Section: J J Russell a N D M S P A L E Lsupporting

confidence: 82%

Purification and Properties of Succinyl‐CoA:3‐Oxo‐Acid CoA‐Transferase from Rat Brain

Russell

Patel

1982

Journal of Neurochemistry

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“…Relative to ketogenesis, little is known about the regulation of mediators of ketone body oxidation. Perhaps paradoxically, expression of the gene encoding CoA transferase (Oxct1), CoA transferase protein abundance, and CoA transferase enzymatic activity are all diminished in rodent heart and muscle during states of sustained ketosis (53,54,71,152,213,228). In pathological contexts such as diabetic ketoacidosis, diminution of CoA transferase abundance and activity limit ketone body disposal, whereas insulin deficiency (or severe impairment of its signaling) stimulates peripheral fatty acid mobilization and unabated hepatic ketogenesis.…”

Section: Ketone Body Metabolismmentioning

confidence: 97%

Ketone body metabolism and cardiovascular disease

Cotter

Schugar

Crawford

2013

American Journal of Physiology-Heart and Circulatory Physiology

374

304

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Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states.

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“…Relatively little is known at the cellular level about SCOT gene and protein expression regulators. Oxct1 mRNA expression and SCOT protein and activity are diminished in ketotic states, possibly through PPAR-dependent mechanisms (Fenselau and Wallis, 1974; Fenselau and Wallis, 1976; Grinblat et al, 1986; Okuda et al, 1991; Turko et al, 2001; Wentz et al, 2010). In diabetic ketoacidosis, the mismatch between hepatic ketogenesis and extrahepatic oxidation becomes exacerbated by impairment of SCOT activity.…”

Section: Regulation Of Hmgcs2 and Scot/oxct1mentioning

confidence: 99%

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

2017

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Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states, and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, recent observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations.

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3-oxo acid coenzyme A-transferase in normal and diabetic rat muscle

Cited by 16 publications

References 17 publications

Purification and Properties of Succinyl‐CoA:3‐Oxo‐Acid CoA‐Transferase from Rat Brain

Purification and Properties of Succinyl‐CoA:3‐Oxo‐Acid CoA‐Transferase from Rat Brain

Ketone body metabolism and cardiovascular disease

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

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