The isoprenoid pathway and the pathogenesis of Reye's syndrome.
The isoprenoid pathway produces three key metabolites: endogenous digoxin (regulator of neurotransmitter uptake), dolichol, and ubiquinone (free radical scavenger). Because a mitochondrial dysfunction has been described in Reye's syndrome, we thought it pertinent to assess the pathway in this disease. Since endogenous digoxin can regulate neurotransmitter transport, the pathway also was assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. The plasma/serum activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone, tryptophan/tyrosine catabolic patterns, free radical, and lipid levels as well as (red blood cell) RBC Na(+)-K(+) ATPase activity were measured in the above mentioned groups.


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(+)-K(+) ATPase activity were reduced. There also was 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.
Kurup
Ravi Kumar
RK
Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India.
Kurup
Parameswara Achutha
PA
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D004077:Digoxin / Q000378:metabolism; D005260:Female; D005609:Free Radicals; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D008297:Male; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D012202:Reye Syndrome / Q000097:blood / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism; D015854:Up-Regulation
D005609:Free Radicals; D011106:Polyisoprenyl Phosphates; D014451:Ubiquinone; D014443:Tyrosine; D004077:Digoxin; D014364:Tryptophan; D006903:Hydroxymethylglutaryl CoA Reductases