Lipid metabolism in human platelets

Abstract

Extracts from human platelets contain the enzymes of de novo fatty acid biosynthesis. The pattern of incorporation of acetate-1-¹⁴C into fatty acids by intact platelets indicates that these enzymes function in platelets. The level of acetyl-coenzyme A (CoA) carboxylase activity in extracts of platelets from normal subjects is 0.036 ±0.01 mμmole of malonyl-CoA formed per min per mg of protein and that of fatty acid synthetase is 0.075 ±0.016 mμmole of malonyl-CoA utilized per min per mg of protein. Thus, platelets are the only formed elements of the blood capable of de novo fatty acid synthesis. The capacity of platelets to synthesize fatty acids is similar to human liver based on enzyme activity per milligram of soluble protein. Acetyl-CoA carboxylase was purified 16-fold from platelet extracts, and this partially purified enzyme was compared to enzyme from rat liver. The two enzymes were similar with respect to requirements, substrate affinities, pH profile of activity, inhibition by malonyl-CoA, and aggregation in the presence of citrate. Thus, while fatty acid synthesis may serve a different function in platelets than in liver, the properties of acetyl-CoA carboxylase from these tissues are alike. The levels of the enzymes of fatty acid synthesis were significantly higher in platelets from splenectomized subjects than in controls. Acetyl-CoA carboxylase levels were 0.086 ±0.027 mμmole of malonyl-CoA formed per min per mg of protein, and fatty acid synthetase levels were 0.151 ±0.039 mμmole of malonyl-CoA utilized per min per mg of protein. These changes in the enzymes of fatty acid synthesis occurred promptly after splenectomy with peak values being reached within 7-10 days.