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In vitro assay demonstrates non-competitive inhibition of hormone-sensitive lipase by lipid metabolites, indicating a feedback mechanism that prevents toxic intracellular fatty acid accumulation.
Hormone-sensitive lipase (HSL) is inhibited in a non-competitive manner by oleoyl CoA, oleic acid and 2-monopalmitoylglycerol, 50% inhibition being observed at concentrations of approx. 0.1 microM, 0.5 microM and 500 microM, respectively. HSL is a key enzyme in lipid metabolism, mobilising triacylglycerol and cholesterol ester stores in several tissues. Feedback inhibition of HSL by oleoyl CoA and oleic acid may therefore prevent accumulation of free fatty acids and cholesterol in the cell, whereas 2-monoacylglycerol may act as a feedback inhibitor if the capacity of monoacylglycerol lipase is exceeded.
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Jepson et al. (1992) studied this question.
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