The Isoprenoid Pathway and the Pathogenesis of Reye's Syndrome

Abstract

u The isoprenoid pathway produces three key metabolites: endogenous digoxin (regulator of neurotransmitter uptake), dolichol, and ubiquinone (free radical scavenger). Since a mitochondrial dysfunction has been described in Reye' s syndrome, it was considered pertinent to assess the pathway in this disease. Since endogenous digoxin can regulate neurotransmitter transport, the pathway was also assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to ¢nd out the role of hemispheric dominance in its pathogenesis. The plasma=serum activity of hydroxy methyl glutaryl (HMG) coenzyme A (CoA) reductase, magnesium, digoxin, dolichol, ubiquinone, tryptophan=tyrosine catabolic patterns, and free radical and lipid levels, as well as RBC Na þ , K þ -ATPase activity, were measured in the groups mentioned. Results: In the patient group as well as in individuals with right hemispheric dominance similar patterns were obtained. There was elevated digoxin and dolichol levels with low levels of ubiquinone in patients with Reye' s syndrome as well as in those with right hemispheric dominance.The serum magnesium and RBC Na þ , K þ -ATPase activity were reduced. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites as well as increased free radical levels. Reye' s syndrome is associated with an upregulated isoprenoid pathway, elevated hypothalamic digoxin secretion, and right hemispheric chemical dominance.