Impact of the intramitochondrial enzyme organization on fatty acid oxidation

The enzymes of mitochondrial beta -oxidation are thought to be organized in at least two functional complexes, a membrane-bound, long-chain-specific b eta -oxidation system and a matrix system consisting of soluble enzymes wit h preferences for medium-chain and short-chain substrates. This hypothesis is supported by the observation that the inactivation of long-chain 3-ketoa cql-CoA thiolase by 4-bromotiglic acid (4-bromo-2-methylbut-2-enoic acid) c auses the complete inhibition of palmitate beta -oxidation el-en though 3-k etoacyl-CoA thiolase, which acts on 3-ketopalmitoyl-CoA, remains partly act ive. The observed substrate specificities of long-chain acyl-CoA dehydrogen ase (LCAD) and very-long-chain acyl-CoA dehydrogenase prompt the suggestion that LCAD is a functional component of the long-chain-specific beta -oxida tion system. Altogether, a view is emerging of the organization of beta -ox idation enzymes in mitochondria that supports the idea of intermediate chan nelling and explains the apparent absence of true intermediates of beta -ox idation from mitochondria.