Mitochondrial biosynthesis of cholesterol in Leydig cells from rat testis.
The subcellular location of some enzymes responsible for cholesterol biosynthesis was studied in metrizamide-purified rat Leydig cells. The highest activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA reductase), a key regulatory enzyme in the cholesterol pathway, was associated with highly enriched mitochondrial fractions with recovery of 62% of the total activity and was located on the inner membrane. A significant part of the activity (35%) was also present in the cytoplasm. The activity of this enzyme in the other subcellular fractions was negligible. The HMG-CoA synthase activity was also found almost entirely in the mitochondria (90%). Otherwise no detectable activity of HMG-CoA lyase was present in the subcellular fractions studied. Furthermore, cholesterol may be synthesized from acetyl-CoA inside the mitochondrion, since a significant incorporation (90%) of [14C]acetyl-CoA into digitonin-precipitable sterols was observed in this organelle and only 10% in the cytoplasmic fraction. The evidence strongly suggests that much of the cholesterol biosynthesis that takes place in Leydig cells is carried out within the mitochondria.
D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002451:Cell Compartmentation; D002784:Cholesterol / Q000096:biosynthesis*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D051381:Rats
D000085:Acetates; D000105:Acetyl Coenzyme A; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases