Fatty acid and cholesterol synthesis from specifically labeled leucine by isolated rat hepatocytes |
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Authors: | Melvin M Mathias Ann C Sullivan James G Hamilton |
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Affiliation: | (1) Roche Research Center, Hoffmann-La Roche Inc., 07110 Nutley, NJ;(2) Present address: Department of Food Science and Nutrition, Colorado State University, 80523 Fort Collins, CO |
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Abstract: | Hepatocytes isolated from female rats meal-fed a high-glucose diet were incubated in Krebs-Henseleit bicarbonate medium containing
16.5 mM glucose,3H2O, and14C-labeled amino acids (−)-Hydroxycitrate depressed the incorporation of3H2O and 14C] alanine into fatty acids and cholesterol. Incorporation of U-14C] leucine into lipids was not affected but incorporation of3H2O 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. |
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Keywords: | |
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