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

FEBS Letters

Infante, Juan P¹  Huszagh, Virginia A¹ 

[1] Institute for Theoretical Biochemistry and Molecular Biology, P.O. Box 4512, Ithaca, NY 14852, USA

关键词: Acyl-CoA dehydrogenase;    Acylcarnitine;    Cardiomyopathy;    Adenine nucleotide translocator;    Neuronal ceroid lipofuscinosis (Batten disease);    Retinopathy;   

DOI  :  10.1016/S0014-5793(00)01083-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A critical analysis of the literature of mitochondrial disorders reveals that genetic diseases of oxidative phosphorylation are often associated with impaired β-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 β-oxidation, producing secondary carnitine deficiency while increasing reactive oxygen species and depleting α-tocopherol (α-TOC). These events result in impairment of the recently elucidated mitochondrial pathway for synthesis of 22:6n-3-containing phospholipids, since carnitine and α-TOC are involved in their biosynthesis. Therapeutic supplementation with 22:6n-3 and α-TOC is suggested.

【 授权许可】

Unknown