Hypothalamic digoxin and isoprenoid pathway dysfunction relation to alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration--relation to hemispheric chemical dominance.
The isoprenoid pathway produces three key metabolites--endogenous digoxin (modulate tryptophan/tyrosine transport), dolichol (important in N-glycosylation of proteins), and ubiquinone (free radical scavenger). It was considered pertinent to assess the pathway in alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration. Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. In the patient group there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites, as well as reduced endogenous morphine synthesis from tyrosine. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Alcoholic cirrhosis, alcoholic addiction, and acquired hepatocerebral degeneration are associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to NMDA excitotoxicity and altered connective tissue/lipid metabolism important in its pathogenesis. Endogenous morphine deficiency plays a role in alcoholic addiction. The same biochemical patterns were obtained in those with right hemispheric chemical dominance. Alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration occur in right hemispheric, chemically dominant individuals.
Kurup
Ravi Kumar
RK
Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India. kvgnair@satyam.net.in
Kurup
Parameswara Achutha
PA
D000328:Adult; D000437:Alcoholism / Q000378:metabolism*; D000704:Analysis of Variance; D002784:Cholesterol / Q000097:blood; D004077:Digoxin / Q000097:blood*; D004198:Disease Susceptibility; D004286:Dolichols / Q000097:blood; D004292:Dominance, Cerebral / Q000502:physiology; D004791:Enzyme Inhibitors / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006001:Glycoconjugates / Q000097:blood; D006025:Glycosaminoglycans / Q000097:blood; D006527:Hepatolenticular Degeneration / Q000378:metabolism*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014364:Tryptophan / Q000097:blood; D014443:Tyrosine / Q000097:blood / Q000378:metabolism; D014451:Ubiquinone / Q000097:blood
D004286:Dolichols; D004791:Enzyme Inhibitors; D006001:Glycoconjugates; D006025:Glycosaminoglycans; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D011106:Polyisoprenyl Phosphates; D014451:Ubiquinone; D014443:Tyrosine; D004077:Digoxin; D014364:Tryptophan; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase