A discoordinate increase in the cellular amount of 3-hydroxy-3-methylglutaryl-CoA reductase results in the loss of rate-limiting control over cholesterogenesis in a tumour cell-free system.
Cholesterol biosynthesis was characterized in cell-free post-mitochondrial supernatant systems prepared from both normal rat liver and Morris hepatoma 3924A. The rate of cholesterol synthesis per cell was 9-fold greater in the tumour system than in that from normal liver, and the tumour systems showed the loss of rate-limiting control at the hydroxymethylglutaryl-CoA reductase (HMGR)-catalysed step. The apparent absence of rate-limiting control over cell-free tumour cholesterogenesis was traced primarily to a discoordinate and dramatic increase in the amount of HMGR in the tumour relative to the liver system. Preliminary evidence for an altered control of the post-lanosterol portion of the pathway was also obtained with the tumour system.
Azrolan
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NI
Department of Biology, New York University, New York 10003.
Coleman
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PS
D000085:Acetates; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002474:Cell-Free System; D002784:Cholesterol / Q000096:biosynthesis*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007810:Lanosterol / Q000032:analysis; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D008798:Mevalonic Acid; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013185:Squalene / Q000032:analysis
D000085:Acetates; D000214:Acyl Coenzyme A; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D007810:Lanosterol; D013185:Squalene; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid