Endogenous hypodigoxinemia-related immune deficiency syndrome.
The isoprenoid pathway produces three key metabolites--digoxin (membrane Na+-K+ ATPase inhibitor, regulator of neurotransmitter transport,  and an immunomodulatory agent), dolichol (a regulator of N-glycosylation of proteins), and ubiquinone (a free radical scavenger). The pathway was assessed in acute rheumatic fever patients with recurrent streptococcal  infections, and who were also studied for differences in right and left hemispheric dominance. The isoprenoid pathway was downregulated with decreased digoxin synthesis in these patients and in those with left hemispheric chemical dominance. The tryptophan catabolites were decreased and the tyrosine catabolites increased. In these groups of patients  the dolichol and glycoconjugate levels were reduced and lysosomal stability was increased. The ubiquinone levels were elevated and free radical levels decreased in these patients. The membrane cholesterol:phospholipid ratios were decreased and membrane glycoconjugates increased. On the other hand in right hemispheric chemical dominance the reverse patterns and hyperdigoxinemia with an upregulated isoprenoid pathway were noticed. The role of the isoprenoid pathway in the pathogenesis of acute rheumatic fever and recurrent streptococcal infections and its relation to hemispheric chemical dominance is discussed.
Kurup
Ravi Kumar
RK
Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India. kvgnair@satyam.net.in
Kurup
Parameswara Achutha
PA
D000208:Acute Disease; D000293:Adolescent; D000704:Analysis of Variance; D002648:Child; D004077:Digoxin / Q000097:blood*; D004198:Disease Susceptibility; D004286:Dolichols / Q000097:blood; D004292:Dominance, Cerebral / Q000502:physiology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000097:blood; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood; D006025:Glycosaminoglycans / Q000097:blood; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D007153:Immunologic Deficiency Syndromes / Q000503:physiopathology*; D008274:Magnesium / Q000097:blood; D016555:Matched-Pair Analysis; D015213:Neuroimmunomodulation / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D010612:Pharyngitis / Q000503:physiopathology; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D012008:Recurrence; D012213:Rheumatic Fever / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013290:Streptococcal Infections / Q000503:physiopathology*; D014451:Ubiquinone / Q000097:blood
D004286:Dolichols; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D006025:Glycosaminoglycans; D018377:Neurotransmitter Agents; D011106:Polyisoprenyl Phosphates; D014451:Ubiquinone; D004077:Digoxin; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium