Secondary carnitine deficiency and impaired docosahexaenoic (22 : 6n-3) acid synthesis: a common denominator in the pathophysiology of diseases of oxidative phosphorylation and beta-oxidation

A critical analysis of the literature of mitochondrial disorders reveals th at genetic diseases of oxidative phosphorylation are often associated with impaired beta-oxidation, and vice versa, and preferentially affect brain, r etina, heart and skeletal muscle, tissues which depend on docosahexaenoic ( 22:6n-3)containing phospholipids for functionality. Evidence suggests that an increased NADH/NAD(+) ratio generated by reduced flux through the respir atory chain inhibits beta-oxidation, producing secondary carnitine deficien cy while increasing reactive oxygen species and depleting alpha-tocopherol (alpha-TOC). These events result in impairment of the recently elucidated m itochondrial pathway for synthesis of 22:6n-3-containing phospholipids, sin ce carnitine and alpha-TOC are involved in their biosynthesis. Therapeutic supplementation with 22:6n-3 and alpha-TOC is suggested. (C) 2000 Federatio n of European Biochemical Societies.