Effects of isoleucine deprivation on synthesis of sterols and fatty acids in LM-cells.
Effects of isoleucine deprivation on synthesis of sterols and fatty acids in LM-cells.
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DOI：
10.1016/s0021-9258(19)69758-9
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发表时间：
1981-03
期刊：
影响因子：
--
通讯作者：
W. Maltese;B. Reitz;J. Volpe
中科院分区：
文献类型：
--
作者：
W. Maltese;B. Reitz;J. Volpe
The effects of isoleucine deprivation on de nouo syn-thesis of sterols and fatty acids have been studied in mouse LM-cells cultured in a chemically defined, lipidfree medium. Removal of isoleucine from the medium resulted in cessation of cell growth (measured by C3H] thymidine incorporation and cell number) within 24 h. Incorporation of [3H] leucine into protein was only slightly affected during this period. The cessation of cell division was accompanied by coordinate decreases in incorporation of radioactivity from [14C] acetate or 3H20 into 3-8-hydroxysterols and fatty acids. The decline in incorporation of 3 H~ 0 into sterols (to 15% of control) was greater than the decline in incorporation of 3H20 into fatty acids (to 50% of control). No change in incorporation of radioactivity from [3H] mevalonolactone into sterols was observed. The decline in sterol synthesis in isoleucine-starved cells was accompanied by suppression of the activities of acetoacetyl-CoA thiolase, 3-hydroxy-3-methylglutaryl-CoA (HMG-GOA) synthase, and HMG-CoA reductase; however, the decline in the activity of the reductase (to 10% of control) paralleled the decrease in sterol synthesis more closely than did the declines in the activities of the thiolase (to 50% of control) and the synthase (to 50% of control). The magnitude of the decrease in the activity of HMG-CoA reductase was not affected by the presence of 50 lll~ NaF in the homogenization and assay solutions. Substantial changes in the activities of acetyl-coA carboxylase or fatty acid synthetase were not observed in conjunction with iso-leucine deprivation, despite the reduction in fatty acid synthesis from 3H20.The cellular concentrations of sterol and fatty acid and the molar ratio of these lipid classes did not undergo substantial alteration after 48 h of isoleucine deprivation. The fact that addition of low density lipoprotein-cholesterol, bovine serum albumin-palmitate, or mevalonate to isoleucine-starved cultures did not prevent arrest of growth, suggests that the declines in sterol synthesis and fatty acid synthesis are consequences of, rather than causes of, the cessation of cell division.
