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Isoprenoid pathway dysfunction in chronic fatigue syndrome

Published online by Cambridge University Press:  24 June 2014

Ravi Kumar Kurup  and
Parameswara Achutha Kurup
Ravi Kumar Kurup
Affiliation:
Department of Neurology, Medical College Hospital, Trivandrum
Parameswara Achutha Kurup*
Affiliation:
Metabolic Disorders Research Center, Trivandrum, Kerala, India
*
Gouri Sadan, T.C.4/1525, North of Cliff House, Kattu Road, Kowdiar P.O.,Trivandrum, Kerala, India. Tel. 0471–2541607; Fax: 91-0471-2550782; E-mail: kvgnair@satyam.net.in
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Abstract

Background and aims:

The isoprenoid pathway was assessed in 15 patients with chronic fatigue syndrome (CFS). The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance has any correlation with these disease states.

Methods:

The isoprenoid metabolites – digoxin, dolichol and ubiquinone – RBC membrane Na+-K+ ATPase activity, serum magnesium and tyrosine/tryptophan catabolic patterns were assessed. The free radical metabolism, glycoconjugate metabolism and RBC membrane composition were also assessed.

Results:

Membrane Na+-K+ ATPase activity and serum magnesium levels were decreased while HMG-CoA reductase activity and serum digoxin levels were increased in CFS. There were increased levels of tryptophan catabolites – nicotine, strychnine, quinolinic acid and serotonin – and decreased levels of tyrosine catabolites –dopamine, norepinephrine and morphine – in CFS. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual glycosaminoglycans (GAG) fractions and lysosomal enzymes in CFS. Reduced levels of ubiquinone, reduced glutathione and free radical scavenging enzymes as well as increased lipid peroxidation products and nitric oxide were noticed in CFS. The biochemical patterns in CFS correlated with those obtained in right hemispheric dominance.

Conclusions:

The role of hypothalamic digoxin and neurotransmitter-induced immune activation, altered glycoconjugate metabolism and resultant defective viral antigen presentation, NMDA excitotoxicity and cognitive and mitochondrial dysfunction in the pathogenesis of CFS is stressed. CFS occurs in individuals with right hemispheric dominance.

Keywords

isoprenoiddigoxindolicholubiquinonechronic fatigue syndrome
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 15 , Issue 5 , October 2003 , pp. 266 - 273
Copyright
Copyright © 2003 Blackwell Munksgaard

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