Hypothalamic digoxin, hemispheric chemical dominance and syndrome X with multiple lacunar state. A hypothesis.
This study assessed the changes in digoxin and some other metabolites of the isoprenoid pathway in metabolic syndrome X presenting with multiple lacunar state. The isoprenoid pathway and digoxin status was also studied for comparison in individuals of differing hemispheric dominance to find out the role of cerebral dominance in the genesis of syndrome X. There was an increase in plasma HMG CoA reductase activity with a consequent increase in serum digoxin, which caused a reduction in RBC membrane Na(+)-K+ ATPase activity. There was an increase in serum tryptophan and its metabolites and a decrease in tyrosine and its metabolites. Serum magnesium was decreased with consequent alteration in the metabolism of glycosaminoglycans and glycolipids. Increase in dolichol, another product of the isoprenoid pathway, resulted in alteration in glycoprotein metabolism. Changes in the composition of membrane glycosaminoglycans, glycoproteins and cholesterol: phospholipid ratio were also observed in this disorder leading to decreased lysosomal stability. Decrease in ubiquinone, another isoprenoid metabolite, resulted in alteration in the free radical generation. Membrane Na(+)-K+ ATPase inhibition due to digoxin, altered membrane structure, increased tryptophan catabolites and decreased tyrosine catabolites can lead to increased intracellular calcium and reduced intracellular magnesium which can account for the symptoms of syndrome X. The biochemical patterns including hyperdigoxinemia observed in syndrome X correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance is a predisposing factor for syndrome X with multiple lacunar state.
Department of Neurology, Medical College, Trivandrum, Kerala, India.
Ravi Kumar
RK
Kurup
Parameswara Achutha
PA
Kurup
D000704:Analysis of Variance; D015161:Dementia, Multi-Infarct / Q000378:metabolism*; D004077:Digoxin / Q000378:metabolism*; D004292:Dominance, Cerebral / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D017566:Microvascular Angina / Q000378:metabolism*; D008875:Middle Aged; D013729:Terpenes / Q000378:metabolism
D013729:Terpenes; D004077:Digoxin