Membrane Na+ K+ ATPase inhibition related dyslipidemia and insulin resistance in neuropsychiatric disorders.
There are several reports in literature implicating cholesterol metabolism in the pathogenesis of neuronal degenerations, oncogenesis, functional neuropsychiatric disorders and multiple sclerosis. Biosynthesis of cholesterol takes place by the isoprenoid pathway, which also produces digoxin, an inhibitor of membrane Na(+)-K+ ATPase. Inhibition of this enzyme results in intracellular Mg++ deficiency which can influence cholesterol metabolism. Digoxin also influences transport of tryptophan and tyrosine which are precursors of various neurotransmitters. Alterations in digoxin, membrane Na(+)-K+ ATPase and also in neurotransmitters have been reported in the disorders mentioned above. In view of this, serum lipid profile, activity of plasma HMG CoA reductase (the major rate limiting step in the isoprenoid pathway), RBC membrane Na(+)-K+ ATPase activity, serum Mg++ concentration, concentration of digoxin and concentration of serum neurotransmitters were studied in some neuropsychiatric disorders. The serum serotonin level was increased while that of serum dopamine and noradrenaline was reduced. Serum digoxin levels were high and RBC membrane sodium-potasium ATPase activity and serum magnesium were reduced. There was a reduction in HDL cholesterol and increase in plasma triglycerides (pattern similar to insulin resistance and syndrome X) in most of the disorders studied. The HMG CoA reductase activity was high, the serum total cholesterol was increased while RBC membrane cholesterol was reduced in most of the cases. The significance of increased digoxin with consequent inhibition of membrane Na(+)-K+ ATPase in relation to changes in cholesterol metabolism and insulin resistance type of dyslipidemia is discussed in this paper.
Kumar
A R
AR
Department of Neurology, Medical College Hospital, Trivandrum, 695 011.
Kurup
P A
PA
D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004829:Epilepsy, Generalized / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000201:enzymology*; D005910:Glioma / Q000201:enzymology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D006949:Hyperlipidemias / Q000097:blood* / Q000201:enzymology; D007333:Insulin Resistance / Q000502:physiology*; D001523:Mental Disorders / Q000097:blood / Q000503:physiopathology*; D017566:Microvascular Angina / Q000201:enzymology; D009103:Multiple Sclerosis / Q000201:enzymology; D009422:Nervous System Diseases / Q000097:blood / Q000503:physiopathology*; D010300:Parkinson Disease / Q000201:enzymology; D012559:Schizophrenia / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood*
D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase