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

Abstract

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

Childhood onset mitochondrial myopathy and lactic acidosis caused by a stop mutation in the mitochondrial cytochrome c oxidase III gene

“…Defects of oxidative phosphorylation downstream of complexes I and II inhibit β oxidation owing to decreased electron transfer from acyl-CoA dehydrogenases to ubiquinone and the intermediates of acyl-CoA β oxidation are released from mitochondria as carnitine esters. 21 Consistent with this, an abnormal lipid accumulation is repeatedly seen in patients with coenzyme Q 10 deficiency. 22 Functional studies on cybrids carrying other COIII mutations located >36 aa downstream from the mutation described here, which is the frameshift mutation leading to a stop at aa position 111 and the 15 bp deletion (missing aa 94-98), confirmed a pathogenic role for both of these mutations with reduction, but not absence, of steady state levels of COX subunits I and II.…”

Influence of vitamin B6 supplementation on polyunsaturated fatty acids concentration in serum and liver of rats fed a diet restricted in protein

“…Fatty acids, n-3, present in fish oil caused decrease of plasma triacylglycerol, however, long-chain monounsaturated fatty acids have only minor effects on this parameter of lipids metabolism [23]. Also genetic disorders of oxidative phosphorylation causing an increased NADH/ NAD(+) ratio are associated with impaired DHA synthesis and secondary carnitine deficiency [24]. The interaction between pyridoxine and fatty acid metabolism may also be mediated by carnitine biosynthesis.…”

Molecular mediators of hepatic steatosis and liver injury

“…As the number of double bonds in PUFAs increase, their rate of peroxidation increases exponentially (81). Mitochondria have a substantial concentration of phospholipids containing docosahexaenoic, which may be essential for functional assembly of the MRC (82). Peroxidation of these mitochondrial membrane components could lead to further diminution of MRC activity and increased cellular oxidative stress.…”