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Inhibition of enoyl-CoA hydratase by long-chainl-3-hydroxyacyl-CoA and its possible effect on fatty acid oxidation

Authors
Journal
Archives of Biochemistry and Biophysics
0003-9861
Publisher
Elsevier
Publication Date
Volume
298
Issue
2
Identifiers
DOI: 10.1016/0003-9861(92)90445-3
Keywords
  • Lipids
  • Lipid Mediators
  • And Glycolipids
Disciplines
  • Biology

Abstract

Abstract The kinetics of bovine liver enoyl-CoA hydratase (EC 4.2.1.17) or crotonase with 2- trans-hexadecenoyl-CoA as a substrate were studied because different rates were obtained with two assay methods based on measurements of substrate utilization and product formation, respectively. l-3-Hydroxyhexadecanoyl-CoA, the product of the crotonase-catalyzed hydration of 2- trans-hexade-cenoyl-CoA, was found to be a strong competitive inhibitor of the enzyme with a K i of 0.35 μ m. In contrast the short-chain product, l-3-hydroxybutyryl-CoA, is a weak competitive inhibitor with a K i of 37 μ m. l-3-Hydroxy-hexadecanoyl-CoA is a much stronger inhibitor of crotonase than are other short-chain and long-chain intermediates of β-oxidation and crotonase is more severely inhibited by this compound than are all β-oxidation enzymes tested so far. Determination of true kinetic parameters for the crotonase-catalyzed hydration of long-chain substrates requires the removal of product in a coupled assay. When this was done, the K m for 2- trans-hexadecenoyl-CoA with bovine liver crotonase was found to be only 9 μ m. It is suggested that under conditions of restricted β-oxidation, when 3-hydroxyacyl-CoAs accumulate in mitochondria, the inhibition of crotonase by long-chain 3-hydroxyacyl-CoAs may limit the further degradation of medium-chain and short-chain intermediates of β-oxidation.

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