Coenzyme Q10 in phenylketonuria and mevalonic aciduria

Mevalonic aciduria (MVA) and phenylketonuria (PKU) are inborn errors of metabolism caused by deficiencies in the enzymes mevalonate kinase and phenylalanine 4-hydroxylase, respectively. Despite numerous studies the factors responsible for the pathogenicity of these disorders remain to be fully characterised. In common with MVA, a deficit in coenzyme Q₁₀ (CoQ₁₀) concentration has been implicated in the pathophysiology of PKU. In MVA the decrease in CoQ₁₀ concentration may be attributed to a deficiency in mevalonate kinase, an enzyme common to both CoQ₁₀ and cholesterol synthesis. However, although dietary sources of cholesterol cannot be excluded, the low/normal cholesterol levels in MVA patients suggests that some other factor may also be contributing to the decrease in CoQ₁₀.The main factor associated with the low CoQ₁₀ level of PKU patients is purported to be the elevated phenylalanine level. Phenylalanine has been shown to inhibit the activities of both 3-hydroxy-3-methylglutaryl-CoA reductase and mevalonate-5-pyrophosphate decarboxylase, enzymes common to both cholesterol and CoQ₁₀ biosynthesis.Although evidence of a lowered plasma/serum CoQ₁₀ level has been reported in MVA and PKU, few studies have assessed the intracellular CoQ₁₀ concentration of patients. Plasma/serum CoQ₁₀ is influenced by dietary intake as well as its lipoprotein content and therefore may be limited as a means of assessing intracellular CoQ₁₀ concentration. Whether the pathogenesis of MVA and PKU are related to a loss of CoQ₁₀ has yet to be established and further studies are required to assess the intracellular CoQ₁₀ concentration of patients before this relationship can be confirmed or refuted.