Year: 1969
Type: article
Abstract: Enzymes of ketogenesiswere measured in homogenates of liver, kidney, brain, intestine, heart, muscle, and three transplantable hepatomas of the rat.Cholesterol synthesis from acetate-Z-W was studied in slices from these tissues.The results show that high levels of P-hydroxy-P-methylglutaryl coenzyme A synthase are unique to liver and the well differentiated hepatomas, and thus provide a biochemical basis for liver's role as the primary ketogenic organ.The ability to synthesize cholesterol from acetate was similar in liver, intestine, and immature brain, all of which contained adequate fl-hydroxy-P-methylglutaryl-CoA synthase to support the observed rates of cholesterogenesis.The failure of the undifferentiated hepatoma 3924A to synthesize acetoacetate or cholesterol from acetate was consistent with its lack of P-hydroxy-/3-methylglutaryl-CoA synthase.It is generally believed that the initial reactions involved in the biosynthesis of cholesterol and acetoacetic acid from ncetyl coenzyme iz are identical (1, 2).These reactions are outlined schematically in Fig. 1.The first two steps are catalyzed by the enzymes /%ketothiolase (acetyl-CoA:acetyl-CoA C-acctyltransferase, EC 2.3.1.9)and &hydro&-methylglutaryl Co.1 synthase (3-hydroxy3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA acetylating), EC 4.1.3.5),respectively.At this point the two pathways diverge, HMG-Cod' lyase (3hydroxy-3-methylglutaryl-Co.4 acetoacetate-lgase, EC 4.1.3.4) catalyzing the formation of acetoacetic acid (Reaction 3) and HhIG-CoA reductase (mevalonate:NADP oxidoreductase (acplating CoA), EC 1.1.1.34)yielding mevalonic acid (Reaction 4).Acetoacetic acid can then be reduced to P-hydroxybutyric acid while mevalonic acid functions as a cholesterol precursor.
Source: Journal of Biological Chemistry
Authors: J D McGarry, D W Foster
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2117008455