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 beta-oxidation system and a matrix system consisting of soluble enzymes with preferences for medium-chain and short-chain substrates. This hypothesis is supported by the observation that the inactivation of long-chain 3-ketoacyl-CoA thiolase by 4-bromotiglic acid (4-bromo-2-methylbut-2-enoic acid) causes the complete inhibition of palmitate beta-oxidation even though 3-ketoacyl-CoA thiolase, which acts on 3-ketopalmitoyl-CoA, remains partly active. The observed substrate specificities of long-chain acyl-CoA dehydrogenase (LCAD) and very-long-chain acyl-CoA dehydrogenase prompt the suggestion that LCAD is a functional component of the long-chain-specific beta-oxidation system. Altogether, a view is emerging of the organization of beta-oxidation enzymes in mitochondria that supports the idea of intermediate channelling and explains the apparent absence of true intermediates of beta-oxidation from mitochondria.
Liang
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Department of Chemistry, City College and Graduate School of the City University of New York, Convent Avenue at 138th Street, New York, NY 10031, U.S.A.
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Zhang
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Schulz
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D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005232:Fatty Acids, Volatile / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity
D005227:Fatty Acids; D005232:Fatty Acids, Volatile; D008565:Membrane Proteins; C116917:acylcarnitine; D010088:Oxidoreductases; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002331:Carnitine