Acetoacetyl-CoA ligase activity in the isolated rat hepatocyte: effects of 25-hydroxycholesterol and high density lipoprotein.
The activity of acetoacetyl-CoA (AcAc-CoA) ligase (E.C.6.2.1.16) in hepatocytes from rats was shown to be the same as the activity in homogenates of their livers. In hepatocytes treated with 25-hydroxycholesterol, AcAc-CoA ligase, 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and rates of sterol synthesis were substantially decreased. Hepatocytes treated with high density lipoprotein (HDL) exhibited a 2 to 4 fold induction of HMG-CoA reductase activity; however an accompanying increase in AcAc-CoA ligase activity and the rate of cholesterol synthesis was not observed. We conclude (a) that increases in the activity of HMG-CoA reductase when mediated by HDL in hepatocytes do not result in a corresponding change in the capacity for sterol synthesis and (b) that changes in the activity state of HMG-CoA reductase can be dissociated from that of AcAc-CoA ligase.
Wong
G A
GA
Department of Biological Chemistry, UCLA School of Medicine 90024.
Bergstrom
J D
JD
Edmond
J
J
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D003066:Coenzyme A Ligases / Q000032:analysis*; D003864:Depression, Chemical; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006888:Hydroxycholesterols / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006888:Hydroxycholesterols; D008075:Lipoproteins, HDL; C007997:25-hydroxycholesterol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D003066:Coenzyme A Ligases; C023747:acetoacetyl-CoA synthetase