No abstract

The recent literature on the putative involvement of a single cycle of peroxisomal L L-oxidation of 24:5n-6 and 24:6n-3 polyunsaturated fatty acids in the biosynthesis of the respective docosapentaenoic (22:5n-6) and docosahexaenoic (22:6n-3) fatty acids is critically reviewed. Present evidence suggests that in vitro data in support of the above proposition is an artifact of a low 2,4-dienoyl-CoA reductase activity due to depletion of NADPH resulting from incubation conditions. Kinetic studies with radiolabeled precursors in cell cultures have shown lower initial rates of labeling of 24:6n-3 than that of 22:6n-3, indicating that 24:6n-3 is an elongation product of 22:6n-3 rather than its precursor. Analysis of other literature data supports the proposal that 22:5n-6 and 22:6n-3 are synthesized in mitochondria via channeled carnitine-dependent pathways involving separate n-6-and n-3-specific desaturases. It is proposed that impaired peroxisomal function in some peroxisomal disorders is a secondary consequence of defective mitochondrial synthesis of 22:6n-3; moreover, some disorders of peroxisomal L L-oxidation show normal or increased 22:5n-6 concentrations, indicating that 22 :5n-6 is synthesized by independent desaturases without peroxisomal involvement.z 1998 Federation of European Biochemical Societies.

A critical analysis of the changes in fatty acid patterns and their metabolism elicited by vitamin E deficiency leads to the proposal that a major role of dietary RRR-K Ktocopherol (K K-TOC) is as an enzymatic precursor of K Ktocopherolquinone (K K-TQ) whose semiquinone radical functions as an essential enzyme cofactor for the fatty acid desaturases of the recently elucidated carnitine-dependent, channeled, mitochondrial desaturation-elongation pathway; a detailed mechanism for its function is proposed. Pathophysiological states produced by vitamin E deficiency and K K-TOC transfer protein defects, such as ataxia, myopathy, retinopathy, and sterility are proposed to develop from the effects of impaired K K-TQdependent desaturases and the resulting deficiency of their polyenoic fatty acid products.z 1999 Federation of European Biochemical Societies.

A critical analysis of the literature of mitochondrial disorders reveals that genetic diseases of oxidative phosphorylation are often associated with impaired L

An analysis of the available data on the cytidine pathway for the synthesis of phosphatidylcholine and phosphatidylethanolamine, by the logic derived from the theoretical principles of metabolic regulation, shows that the first two reactions catalysed by choline (ethanolamine) kinase and phosphocholine (phosphoethanolamine) cytidylyltransferase are rate-limiting, whereas the phosphocholine (phosphoethanolamine) transferase step is near equilibrium in rat liver.