Regulation of ketone body metabolism in skeletal muscle

1. A combination of isotope-dilution and arteriovenous-difference techniques was used to determine the significance of ketones to energy homoeostasis in fasted pregnant ewes.2. There was incomplete interconversion of D(−) 3-hydroxybutyrate (3HB) and acetoacetate (AcAc) and therefore neither entry rate nor oxidation of total ketone bodies could be estimated by assuming circulating ketone bodies represent a single metabolic compartment. Total ketone body metabolism was satisfactorily summarized using a three-compartment model. In fasted pregnant ewes the mean entry rate of total ketones was 1 mmol/h per kg body-weight and of the ketones entering the circulation 87% were promptly oxidized to carbon dioxide accounting for 30% of the total COa production.3. Ketone bodies are readily utilized by hind-limb skeletal muscle such that if completely oxidized, 18±4 and 48±3% of the oxygen utilized could be accounted for in fed and fasted pregnant ewes respectively. For both 3HB and AcAc there was a hyperbolic relationship between utilization and arterial concentration. The apparent Michaelis constant (Km) values were 0·55 and 1–42 mM respectively and the maximum velocity (Vmax) 2·9 and 5·6 mmol/h per kg muscle. The arterial concentration of AcAc is always below the Km value and this limits the utilization rate. The D(−) 3HB concentration, however, may surpass that required for maximum utilization and ketoacidosis may be a consequence of this.4. A two-compartment model was used to analyse ketone body metabolism by hind-limb skeletal muscle. The results suggested substantial intercon version and production of AcAc and 3HB.5. The pregnant uterus utilized 3HB which if completely oxidized accounted for 12±2 (fed) and 25±4 (fasted) % of its O2 consumption. At least 64% of the net 3HB utilized was oxidized. AcAc was not utilized in significant quantities.

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Ketone body metabolism in normal and diabetic human skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.249.2.e131 ◽

1985 ◽

Vol 249 (2) ◽

pp. E131-E136 ◽

Cited By ~ 1

Author(s):

R. Nosadini ◽

A. Avogaro ◽

L. Sacca ◽

C. Vigorito ◽

S. de Kreutzenberg ◽

...

Keyword(s):

Skeletal Muscle ◽

Steady State ◽

Human Skeletal Muscle ◽

Ketone Body ◽

Ketone Bodies ◽

Normal Subjects ◽

Priming Dose ◽

Tracer Concentration ◽

Ketone Body Metabolism ◽

Forearm Muscle

Although the liver is considered the major source of ketone bodies (KB) in humans, these compounds may also be formed by nonhepatic tissues. To study this aspect further, 3-[14C]hydroxybutyrate (BOH) or [3-14C]acetoacetate (AcAc) were constantly infused after a priming dose and contemporaneous arterial and venous samples were taken at splanchnic, heart, kidney, and leg sites in eight normal subjects (N) undergoing diagnostic catheterization and at the forearm site in five normal and six ketotic diabetic (D) subjects. After 70 min of infusion, tracer and tracee levels of AcAc and BOH reached a steady state in the artery and vein in both normal and diabetic subjects. The venous-arterial (V-A) difference at the forearm step for cold KB was negligible both in normal and diabetic subjects, whereas for labeled KB it was approximately 10-fold higher in diabetic subjects (V-A AcAc, -31 +/- 7 and -270 +/- 34 dpm/ml in N and D, respectively; V-A BOH, -38 +/- 6 and -344 +/- 126 dpm/ml in N and D, respectively). We assumed that the V-A difference in tracer concentration was consistent with dilution of the tracer by newly synthesized tracee inside the muscle and calculated that the forearm muscle produces KB at a rate of 16.2 +/- 3.3 mumol/min in D and 0.9 +/- 0.9 mumol/min in N. These findings can be accounted for by the hypothesis that the disappearance flux of KB from circulation was replaced by an equivalent flux of KB entering the vein at the muscle step in D but not in N. Moreover, in N KB were not only produced but also utilized by the splanchnic area (39 +/- 9 mumol/min).(ABSTRACT TRUNCATED AT 250 WORDS)

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34-OR: Maladaptive Increases in Skeletal Muscle Ketone Body Oxidation Contribute to Dysglycemia in Mice Subjected to Experimental Obesity

Diabetes ◽

10.2337/db19-34-or ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 34-OR

Author(s):

RAMI AL BATRAN ◽

KESHAV GOPAL ◽

JADIN J. CHAHADE ◽

JOHN R. USSHER

Keyword(s):

Skeletal Muscle ◽

Ketone Body

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Ketone body metabolism in NIDDM. Effect of sulfonylurea treatment

Diabetes ◽

10.2337/diabetes.41.8.968 ◽

1992 ◽

Vol 41 (8) ◽

pp. 968-974 ◽

Cited By ~ 1

Author(s):

A. Avogaro ◽

A. Valerio ◽

L. Gnudi ◽

A. Maran ◽

M. Zolli ◽

...

Keyword(s):

Ketone Body ◽

Ketone Body Metabolism

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Faculty Opinions recommendation of Ketone body metabolism and cardiovascular disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718541563.793499082 ◽

2014 ◽

Author(s):

Heinrich Taegtmeyer

Keyword(s):

Cardiovascular Disease ◽

Ketone Body ◽

Ketone Body Metabolism

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Enzymes of Ketone Body Metabolism

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)69522-5 ◽

1960 ◽

Vol 235 (2) ◽

pp. 318-325 ◽

Cited By ~ 8

Author(s):

George I. Drummond ◽

Joseph R. Stern

Keyword(s):

Ketone Body ◽

Ketone Body Metabolism

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Mammary blood flow and ketone body metabolism in normal, fasted, and ketotic cows

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1968.215.1.218 ◽

1968 ◽

Vol 215 (1) ◽

pp. 218-227 ◽

Cited By ~ 75

Author(s):

DS Kronfeld ◽

F Raggi ◽

Ramberg CF

Keyword(s):

Blood Flow ◽

Ketone Body ◽

Ketone Body Metabolism

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The life and work of Dermot Hedley (‘Derek’) Williamson (1929–1998)

Biochemical Society Transactions ◽

10.1042/bst0290237 ◽

2001 ◽

Vol 29 (2) ◽

pp. 237-240

Author(s):

R. D. Evans ◽

M. Stubbs ◽

G. F. Gibbons ◽

E. A. Newsholme

Keyword(s):

Metabolic Pathways ◽

Metabolic Regulation ◽

Ketone Body ◽

Scientific Discovery ◽

Lipid Synthesis ◽

Acid Oxidation ◽

Citation Classic ◽

Integrated Regulation ◽

Ketone Body Metabolism

Derek Williamson's scientific career spanned the ‘Golden Age’ of research into metabolic regulation, to which he made an important and sustained contribution. Derek joined Hans Krebs' laboratory at Sheffield University in 1946 and moved to Krebs' MRC Unit in Oxford in 1960. He elaborated an enzymic method for the determination of acetoacetate and 3-hydroxybutyrate [Williamson, Mellanby and Krebs, Biochem. J. (1962) 82, 90–96], which opened up the field of ketone body metabolism and its regulation and became a Citation Classic. Another Citation Classic followed [Williamson, Lund and Krebs, Biochem. J. (1967) 103, 514–527]. He moved with Krebs to the Metabolic Research Laboratory at the Radcliffe Infirmary in 1967, where he blossomed, formulating his ideas about the integrated regulation of metabolic pathways, particularly with regard to fatty acid oxidation, lipid synthesis and ketone body metabolism. His success was illustrated by more than 200 publications. Derek implanted and nurtured a sense of the excitement of scientific discovery in his colleagues and students, and he worked hard to provide a friendly, supportive and encouraging environment. Many lives have been enriched by the privilege of working with him.

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