Pseudoketogenesis in the perfused rat heart

Journal Article · Mon Dec 05 04:00:00 EST 1988 · J. Biol. Chem.; (United States)

OSTI ID:6786447

Fink, G; Desrochers, S; Des Rosiers, C; Garneau, M; David, F; Daloze, T; Landau, B R; Brunengraber, H

Ketogenesis is usually measured in vivo by dilution of tracers of (3R)-hydroxybutyrate or acetoacetate. We show that, in perfused working rat hearts, the specific activities of (3R)-hydroxybutyrate and acetoacetate are diluted by isotopic exchanges in the absence of net ketogenesis. We call this process pseudoketogenesis. When hearts are perfused with buffer containing 2.3 mM of (4-3H)- plus (3-14C)acetoacetate, the specific activities of (4-3H) and (3-14C)acetoacetate decrease while C-1 of acetoacetate becomes progressively labeled with 14C. This is explained by the reversibility of reactions catalyzed by mitochondrial 3-oxoacid-CoA transferase and acetoacetyl-CoA thiolase. After activation of labeled acetoacetate, the specific activity of acetoacetyl-CoA is diluted by unlabeled acetoacetyl-CoA derived from endogenous fatty acids or glucose. Acetoacetyl-CoA thiolase partially exchanges 14C between C-1 and C-3 of acetoacetyl-CoA. Finally, 3-oxoacid-CoA transferase liberates weakly labeled acetoacetate which dilutes the specific activity of extracellular acetoacetate. An isotopic exchange in the reverse direction is observed when hearts are perfused with unlabeled acetoacetate plus (1-14C)-, (13-14C)-, or (15-14C)palmitate; here also, acetoacetate becomes labeled on C-1 and C-3. Computations of specific activities of (3R)-hydroxybutyrate, acetoacetate, and acetyl-CoA yield minimal rates of pseudoketogenesis ranging from 19 to 32% of the net uptake of (3R)-hydroxybutyrate plus acetoacetate by the heart.

• Research Organization: Univ. of Montreal (Canada)
• OSTI ID: 6786447
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 263:34; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETOACETATES
ANIMALS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
ENZYME ACTIVITY
ENZYMES
HEART
ISOTOPE APPLICATIONS
ISOTOPE DILUTION
ISOTOPIC EXCHANGE
LABELLED COMPOUNDS
MAMMALS
METABOLISM
MITOCHONDRIA
ORGANOIDS
ORGANS
PERFUSED ORGANS
RATS
RODENTS
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
VERTEBRATES