Hostname: page-component-7b7567c8c-wxvwp Total loading time: 0 Render date: 2026-11-14T08:16:14.842Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get accessRights & Permissions [Opens in a new window]

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

Information

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Shafran, S.The chronic fatigue syndrome. Am J Med 1991;90: 730–739.CrossRefGoogle ScholarPubMed
Wessely, S.Chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 1991;54: 669–671.CrossRefGoogle ScholarPubMed
Kennard, C.Recent Advances in Clinical Neurology. Edinburgh: Churchill Livingston, 1990. Google Scholar
Goldstein, JL, Brown, MS.Regulation of the mevalonate pathway. Nature 1990;343: 425–430.CrossRefGoogle ScholarPubMed
Haupert, GT.Sodium pump regulation by endogenous inhibition. Top Membr Transport 1989;34: 345–348. Google Scholar
Rao, AV, Ramakrishnan, S.Estimation of HMG CoA reductase activity. Clin Chem 1975;21: 1523–1528.Google Scholar
Wallach, DFH, Kamath, VB.Methods in Enzymology 8. New York: Academic Press, 1966. Google Scholar
Arun, P, Ravi Kumar, A, Leelamma, S, Kurup, PA.Identification and estimation of endogenous digoxin in biological fluids and tissues by TLC and HPLC. India J Biochem Biophys 1998;35: 308–312. Google ScholarPubMed
Palmer, DN, Maureen, AA, Robert, DJ.Separation of some neutral lipids by normal phase high performance liquid chromatography on a cyanopropyl column: ubiquinone, dolichol and cholesterol levels in sheep liver. Anal Biochem 1984;140: 315–319.CrossRefGoogle ScholarPubMed
Price, WJ.Spectrochemical Analysis by Atomic Absorption. New York: John Wiley, 1985. Google Scholar
Bloxam, DL, Warren, WH.Error in the determination of tryptophan by the method of Denkala and Dewey. A revised procedure. Anal Biochem 1974;60: 621–625.CrossRefGoogle Scholar
Wong, PWK, O'Flynn, ME, Inouye. Flourimetric method for tyrosine. Clin Chem 1964;10: 1098–1100. Google Scholar
Curzon, G, Green, AR.Rapid method for the determination of 5-hydroxy tryptamine and 5-hydroxy indoleacetic acid in certain regions of rat brain. Br J Pharmacol 1970;39: 653–655.CrossRefGoogle Scholar
Well-Malherbe, S.Methods of Biochemical Analysis. New York: Inter Science, 1971. Google Scholar
Arun, P, Ravi Kumar, A, Leelamma, S, Kurup, PA.Endogenous alkaloids in the brain of rats loaded with tyrosine/tryptophan and in the serum of patients of neurodegenerative and psychiatric disorders. Ind J Med Res 1998;107: 231–238. Google ScholarPubMed
Manoj, AJ, Kurup, PA.Changes in the glycosaminoglycans and glycoproteins in the rat brain during protein calorie malnutrition. J Clin Biochem Nutr 1998;25: 149–157. Google Scholar
Lowenstein, JM.Methods in Enzymology 25. New York: Academic Press, 1979. Google Scholar
Kakkar, P, Das, B, Viswanathan, PN.A modified spectrophotometric assay of SOD. Indian J Biochem Biophys 1984;21: 130.Google Scholar
Maehly, AC, Chance, B.The assay of catalase and peroxidase. Meth Biochem Anal 1971;2: 357. Google Scholar
Paglia, DE, Valentine, WN.Studies on quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Laboratory Clin Med 1979;70: 158. Google Scholar
Horn, HD, Burns, Fh.Methods of Enzymatic Analysis. New York: Academic Press 1978. Google ScholarPubMed
Will, ED.Lipid peroxide formation in microsomes – general consideration. Biochem J 1969;113: 315.CrossRefGoogle Scholar
Brien, PJ O.Estimation of conjugated dienes and hydroperoxide. Can J Biochem 1969;47: 485.Google Scholar
Beutler, E, Duran, O, Kelley, BM.Modified procedure for the estimation of reduced glutathione. J Laboratory Clin Med 1963;61: 882. Google Scholar
Rammel, CG, Cunlifee, B, Keiboom, AJ.Determination of alpha tocopherol in biological specimens by high performance liquid chromatography. J Liquid Chromatogr 1983;6: 1123. CrossRefGoogle Scholar
Gabor, G, Allon, N.Spectrofluorometric method for NO determination. Anal Biochem 1994;220: 16.CrossRefGoogle ScholarPubMed
Wootton, IDP.Estimation of iron binding capacity. Micro-Anal Med Biochem 1964;4: 124. Google Scholar
Henry, RJ, Chiamori, N, Jacobs, SL, Segalov, M.Estimation of ceruloplasmin. Proc Soc Exp Biol Medical 1960;104: 620. CrossRefGoogle Scholar
Spencer, K, Price, CP.The determination of serum albumin using bromocresol green. Am Clin Biochem 1977;14: 105. CrossRefGoogle Scholar
Falholt, K, Lund, B, Fatholt, W.Estimation of free fatty acids. Clin Chem Acta 1973;46: 105. CrossRefGoogle Scholar
Ravi Kumar, A, Jyothi, A, Kurup, PA.14C-acetate incorporation into digoxin in rat rain and effect of digoxin administration. Ind J Exp Biol 2001;3: 420–426. Google Scholar
Haga, H.Effects of dietary magnesium supplementation on diurnal variation of BP and plasma sodium-potassium ATPase activity in essential hypertension. Jpn Heart J 1992;33: 785.CrossRefGoogle Scholar
Finkel, TH.T-cell development and transmembrane signaling. Changing biological responses through a unchanging receptor. Immunol Today 1991;12: 79.CrossRefGoogle ScholarPubMed
Ashkenazi, A, Dixit, VM.Death receptors signaling and modulation. Science 1998;281: 1305.CrossRefGoogle ScholarPubMed
Hisaka, A, Kasamatu, S, Takenaga, N.Absorption of a novel prodrug of DOPA. Drug-Metabolism Disposal 1990;18: 261. Google ScholarPubMed
Wyllie, E.Basic neurophysiology of epilepsy. In: Treatment of Epilepsy: Principles and Practice. Baltimore: William and Wilkins, 1996. Google Scholar
Carpenter, WT Jr,Buchanan, RW.Medical progress in schizophrenia. New Engl J Med 1994;30: 681–690. CrossRefGoogle Scholar
Greenamyre, JT, Poter, RHP.Anatomy and phsysiology of glutamate in CNS. Neurolory 1994;44: 7. Google Scholar
Felton, DF, Cohen, N, Ader, R. Psychoneuroimmunology. New York: Academic Press, 1991. Google Scholar
Jaya, P, Kurup, PA.Effect of magnesium deficiency on the metabolism of glycosaminoglycans in rats. J Biosci 1986;10: 487. CrossRefGoogle Scholar
Monia, BP, Ecker, J, Crooke, ST.Ubiquitination. Enzymes Biotechnol 1990;8: 209. Google Scholar
Ploegh, HL.Viral strategies for immune evasion. Science 1998;280: 248.CrossRefGoogle ScholarPubMed
Linstinsky, JL, Siegal, GP, Listinsky, MC.Alpha-L-fucose, a potentially critical molecule in pathologic processes including neoplasia. Am J Clin Pathol 1998;110: 425.CrossRefGoogle Scholar
Wiedemann, C, Cockcroft, S.Vesicular transport. Nature 1998;394: 426.CrossRefGoogle ScholarPubMed
Green, DR, Reed, JC.Mitochondria and apoptosis. Science 1998;281: 1309.CrossRefGoogle ScholarPubMed
Olanow, WC, Arendash, GW.Metals and free radicals in neurodegenerative disorder. Curr Opin Neurol 1994;7: 548.CrossRefGoogle Scholar
Stoye, J.Endogenous proviruses as ‘mementos’. Nature 1997;388: 840.CrossRefGoogle Scholar
Li, E, Beard, C, Jaenisch, R.Role of DNA methylation in genomic imprinting. Nature 1993;366: 362.CrossRefGoogle ScholarPubMed