The regulation of fatty acid chain elongation in rat liver microsomes: role of fasting and CoASH.

The elongation system for palmitic acid in rat liver microsomes was decreased to 1/3 by fasting, while the elongation of eicosapentaenoic acid was not sensitive to fasting. The rate of eicosapentaenoic acid elongation in the fed state was 50% higher than using palmitic acid as a substrate. The saturated and polyunsaturated fatty acyl-CoA substrates exhibited positive cooperativity on the rate-limiting condensing step in the elongation system, with a Hill constant of approx. 2. An inhibition by CoASH on the total elongation reaction as well as on the condensation step was demonstrated using acyl-CoA substrates, and followed a hyperbolic pattern. The concentrations giving a 50% inhibition (30-70 microM) were in the range found in rat hepatocyte cytosol, indicating that free CoASH has the potential to act as a physiological regulator.