Isoprenoid biosynthesis in multiple sclerosis, II. A possible role of NADPH

Genetic predisposition in MS, influence of fat consumption on the disease, and excretion of lipid metabolites in urine led us to investigate isoprenoid metabolism in this disease. Ubiquinone concentration and biosynthesis was normal in lymphocytes. Cytochrome oxidase, which contains an isoprenoid side chain, was normal in activity. Cholesterol biosynthesis from acetate was found to be elevated in MS, and so was triglyceride biosynthesis. Increased biosynthesis may offer a very simple explanation to all the metabolites excreted (3-methylglutaconic acid, 2-hydroxy-2-methyl-3-butenoic acid and adipic acid). Increased biosynthesis may be caused by an elevated NADPH/NADP ratio, since such an elevation may also account for many other biochemical anomalies in MS. Elevated NADPH/NADP ratio may be of direct importance in the pathogenesis.