Mammalian fatty acid synthetase: evidence for subunit identity and specific removal of the thioesterase component using elastase digestion

Abstract

Mammalian fatty acid synthetase is a multifunctional enzyme containing 7 enzyme activities and an acyl carrier function on only 2 polypeptide chains [ 11. These 2 polypeptides both have mol. wt 250 000 and cannot be resolved by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate [2-4]. However it has not been clear whether or not the subunits are identical. In this paper we present information on the cleavage of rabbit mammary gland fatty acid synthetase by elastase, which is difficult to reconcile with the view that the subunits are different. If our view is correct, fatty acid synthetase represents a remarkable sample of a multifunctional polypeptide, with 7 activities and a prosthetic group on one polypeptide chain. We also show that the first cleavage by elastase specifically removes the thioesterase component. This causes inactivation of fatty acid synthetase despite the fact that all 7 partial enzyme activities are unimpaired.