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 that genetic diseases of oxidative phosphorylation are often associated with impaired beta-oxidation, and vice versa, and preferentially affect brain, retina, 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 respiratory chain inhibits beta-oxidation, producing secondary carnitine deficiency while increasing reactive oxygen species and depleting alpha-tocopherol (alpha-TOC). These events result in impairment of the recently elucidated mitochondrial pathway for synthesis of 22:6n-3-containing phospholipids, since carnitine and alpha-TOC are involved in their biosynthesis. Therapeutic supplementation with 22:6n-3 and alpha-TOC is suggested.
Infante
J P
JP
Institute for Theoretical Biochemistry, Ithaca, NY, USA. instittheorbiochem@netscape.net
Huszagh
V A
VA
D000818:Animals; D002331:Carnitine / Q000172:deficiency*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000178:diet therapy / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D017237:Mitochondrial Encephalomyopathies / Q000178:diet therapy / Q000503:physiopathology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000178:diet therapy / Q000503:physiopathology; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010743:Phospholipids / Q000096:biosynthesis; D014810:Vitamin E / Q000378:metabolism / Q000627:therapeutic use
D010743:Phospholipids; D014810:Vitamin E; D004281:Docosahexaenoic Acids; D002331:Carnitine