β‐Oxidation of fatty acids

Regulatory aspects, genetic defects, structure and mechanisms of acyl-CoA dehydrogenases and oxidases The b-oxidation of fatty acids is a central metabolic process providing electrons to the respiratory chain and thus energy for a multitude of needs in aerobic organisms. It is a complex process occurring inside mitochondria, involves more than a dozen enzymes and must be carefully regulated, in particular in its relationship to the other sources of energy such as carbohydrate and amino acid catabolism. The consequences of dysfunctions in b-oxidation can be many-fold and severe with regard to human health, and thus an understanding of the basic mechanisms is of great relevance. The scope of the present series of minireviews is to highlight aspects of b-oxidation from different, complementary points of view. Thus, in the first review, Bartlett and Eaton address the interplay and regulation of the various enzymes involved in the b-oxidation cycle itself, and of those involved in the transport and transformation of fatty acids and conjugates. They also deal with the effects of malfunction of these enzymes, e.g. as a consequence of genetic defects. The second review is by Gregersen, Bross and Andresen and addresses a topic that has increased in importance in the recent past: the consequences on human health of genetic defects affecting b-oxidation. Since the discovery of the first defects in the 1970s, this field has gained steadily in relevance. One reason is undoubtedly the central role of b-oxidation in Ôenergy metabolismÕ. The second is associated with the finding that one specific mutation affecting medium-chain acyl-CoA dehydrogenase is among the most common genetic defects in humans of Caucasian descent, its frequency being higher than that of phenylketonuria. This has spurred great advances in the methodologies for the detection of specific metabolites in clinical chemistry, in genetic analysis and by this in the identification of specific defects. The review also draws attention to the importance of the interplay of medical studies with basic biochemical investigations that aim to elucidate the molecular basis of genetic defects. The third (Kim and Miura) and fourth contributions (Ghisla and Thorpe) deal with the family of enzymes involved in b-oxidation that has received most attention recently: the enzymes involved in the first step of the cycle, the a,b-dehydrogenation of fatty acid acyl-CoA conjugates. These enzymes constitute a family of flavoproteins whose chemistries regarding the catalytic event are similar. However , they differ significantly in their specificity, tissue distribution …