Fatty acid and cholesterol synthesis from specifically labeled leucine by isolated rat hepatocytes.
Hepatocytes isolated from female rats meal-fed a high-glucose diet were incubated in Krebs-Henseleit bicarbonate medium containing 16.5 mM glucose, 3H2O, and 14C-labeled amino acids (-)-Hydroxycitrate depressed the incorporation of 3H2O and [14C] alanine into fatty acids and cholesterol. Incorporation of [U-14C]leucine into lipids was not affected but incorporation of 3H2O into lipids was decreased significantly by (-)-hydroxycitrate. (-)-Hydroxycitrate depressed the incorporation of radioactivity from [2-14C]leucine into fatty acids and cholesterol by 61 and 38%, respectively, and stimulated the incorporation of radioactivity from [4,5-3H]leucine 35 and 28%. As [2-14C]leucine labels the acetyl-CoA pool and [4,5-3H]leucine labels the acetoacetate pool, it was concluded that mitochondrial 3-hydroxy-3-methylglutaryl-CoA is not incorporated intact into cholesterol, and that acetoacetate can be activated effectively in the liver cytosol for support of cholesterol and fatty acid synthesis.
D000090:Acetoacetates; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000409:Alanine / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis*; D002951:Citrates / Q000494:pharmacology; D005227:Fatty Acids / Q000096:biosynthesis*; D005260:Female; D007651:Keto Acids / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D000090:Acetoacetates; D002951:Citrates; D005227:Fatty Acids; D007651:Keto Acids; C016635:acetoacetic acid; D000105:Acetyl Coenzyme A; C007999:hydroxycitric acid; D002784:Cholesterol; D007930:Leucine; D000409:Alanine