Isoprenoid pathway-related membrane dysfunction in neuropsychiatric disorders.
The membrane composition and the isoprenoid pathway metabolites important in maintaining cell membrane integrity was studied in neurological and psychiatric disorders. The results indicate alteration in cholesterol:phospholipid ratio of the RBC membrane which is increased in glioma, schizophrenia, and bipolar mood disorder (MDP); decreased in multiple sclerosis and Parkinson's disease; and not significantly altered in epilepsy. The concentration of total glycosaminoglycans (GAG), hexose, and fucose decreased in the RBC membrane and increased in the serum. The RBC membrane Na+-K+ ATPase activity was reduced and serum HMG CoA reductase activity was increased. There were increased serum levels of digoxin, cholesterol, and dolichol and decreased levels of ubiquinone. The serum magnesium and tyrosine levels were reduced and tryptophan increased. The results indicate a defect in membrane formation and a decreased membrane Na+-K+ ATPase activity in all the disorders studied.  The results are discussed, and a hypothesis regarding the relationship between these disorders and defective membrane architecture and membrane Na+-K+ ATPase inhibition is presented.
Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India.
Ravi Kumar
RK
Kurup
Parameswara Achutha
PA
Kurup
D000328:Adult; D002784:Cholesterol / Q000097:blood; D004077:Digoxin / Q000097:blood; D004286:Dolichols / Q000097:blood; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D001523:Mental Disorders / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D009422:Nervous System Diseases / Q000097:blood / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010743:Phospholipids / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood; D013729:Terpenes / Q000097:blood*; D014364:Tryptophan / Q000097:blood; D014443:Tyrosine / Q000097:blood; D014451:Ubiquinone / Q000097:blood
D004286:Dolichols; D008565:Membrane Proteins; D010743:Phospholipids; D013729:Terpenes; D014451:Ubiquinone; D014443:Tyrosine; D004077:Digoxin; D014364:Tryptophan; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase