ROSENTHAL, J., A. ANGEL, AND J. FARKAS. Metabolic fate of leucine: a sign $ kant sterol precursor in adipose tissue and muscle. Am. J. Physiol. 226 (2): 411-418. 1974.-The quantitative significance of muscle and adipose tissue as extrahepatic sites of leucine metabolism was studied. The rate of leucine conversion to either CO* or total lipid expressed per gram wet weight of tissue was adipose tissue> muscle> liver. Insulin increased the rate of leucine conversion to total lipids and sterols in adipose tissue but not in muscle or liver. The incorporation of leucine to protein was greatest in liver, followed by adipose tissue, then muscle. In terms of total organ activity, leucine utilization(ie, conversion to CO2+ total lipid+ protein) in adipose tissue and muscle combined was 7 times greater than that of liver. Leucine conversion to nonsaponifi-able lipids in adipose tissue and muscle combined exceeded that occurring in liver. The incorporation of leucine carbons into fatty acid and nonsaponifiable lipids in adipose tissue was linear over physiological concentrations of substrate (0. ll. O mM). Both leucine and glucose served equally well in the synthesis of nonsaponifiable lipids in adipose tissue. Thus, adipose tissue and muscle are major extrahepatic sites of leucine metabolism, and leucine is a significant precursor for sterol biosynthesis in adipose tissue. adipose tissue metabolism; liver; leucine metabolism; cholesterol synthesis

THERE IS considerable evidence suggesting that the metabolic degradation of leucine occurs primarily at peripheral sites (16, 20, 23, 30). Indeed, transamination of leucine and other branched-chain amino acids is mainly a function of the extrahepatic tissues (20). Leucine is metabolized through several intermediary steps to P-hydroxy-P-methylglutaryl-CoA (HMG-CoA), a direct precursor of cholesterol (24). Since HMG-CoA can be further converted to acetoacetate and acetyl-CoA, it is clear that leucine can serve as a potential precursor of several major classes of lipids including cholesterol (24). Recently, Miettinen and Penttila (27) have demonstrated that in the human leucine may be an important precursor of serum cholesterol and that muscle may be the major extrahepatic source of cholesterol newly synthesized from leucine (26). Numerous investigations have shown that adipose tissue and isolated fat cells from rats and mice can convert L-leucine into protein, fatty acid, and carbon dioxide (7, 14, 18, 23, 33). This report examines the quantitative significance of leucine incorporation into protein, carbon dioxide, fatty acid, and sterols in rat adipose tissue and cells by comparing it with that of muscle and liver. The results