Impact of the intramitochondrial enzyme organization on fatty acid oxidation

Abstract

T h e enzymes of mitochondrial /3-oxidation are thought to be organized in at least two functional complexes, a membrane-bound, long-chainspecific P-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 P-oxidation even though 3-ketoacylCoA thiolase, which acts on 3-ketopalmitoyl-CoA, remains partly active. T h e 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-chainspecific /3-oxidation system. Altogether, a view is emerging of the organization of p-oxidation enzymes in mitochondria that supports the idea of intermediate channelling and explains the apparent absence of true intermediates of /3-oxidation from mitochondria.

Conjugated linoleic acid isomers in mitochondria

“…This contrasts with the sequestration of CoA as cis-13 docosenoyl-CoA (erucoyl-CoA) reported in heart mitochondria during rapeseed oil feeding (42). Further, octanoyl-CoA entering the strict ␤-oxidative cycle was dehydrogenated through the activity of a medium-chain acyl-CoA dehydrogenase (MCAD) (42,43), which allowed it to bypass the step devoted to long-chain acyl-CoA dehydrogenation (possibly unsuitable for CLA-CoA). As the oxidation of octanoate, after prior respiration on either CLA, was inhibited under carnitine-dependent conditions, the inhibition must have occurred after the entry of acyl moieties into mitochondria and before the ␤-oxidative reactions, i.e., at the CAT II-catalysed step.…”

Mitochondrial β‐oxidation in Aspergillus nidulans

“…While disruption of echA caused a serious restriction of growth on long-chain fatty acids, the capacity of this pathway to actually degrade substrates as long as oleic acid, C 18 , or erucic acid, C 22 , remains to be determined. The equivalent enoyl-CoA hydratases from mammals have activity with chain lengths from C 4 to C 16 , but the pathway as a whole has very little activity with C 16 (Fong and Schulz, 1977;Liang et al, 2001). The substrate specificities of the acyl-CoA dehydrogenases (first step) are much more specialized (Ikeda et al, 1985), making identification and characterization of these enzymes important for defining the specificity of the pathway.…”

Skeletal Muscle Lipid Metabolism in Exercise and Insulin Resistance

“…Therefore, when acetyl CoA is accumulating the thiolase is inhibited and accordingly so is ␤-oxidation. In fact, inactivation of the thiolase causes the complete inhibition of palmitate ␤-oxidation (177). Thus high concentrations of acetyl CoA, as observed during intense exercise in muscle (49,62,203) or when muscle glycogen levels are high (221,234), may tend to slow ␤-oxidation by inhibition of ␤-keto acyl CoA thiolase.…”