Isoprenoid Pathway Related Cascade in Multiple Myeloma

Ravi Kumar KURUP1, Rekha A NAIR2, Parameswara Achutha KURUP3

1Department of Neurology, Medical College Hospital, Kerala, India
2II. Department of Pathology, Regional Cancer Center, Kerala, India
3Metabolic Disorders Research Center, Kerala, India


This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol and ubiquinone in multiple myeloma. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition and free radical metabolism. There was elevation in plasma HMG CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na+ - K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, nicotine, strychnine and quinolinic acid were elevated while tyrosine, dopamine, noradrenaline and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose and fucose residues of glycoproteins, cholesterol and phospholipids were reduced. The activity of all free radical scavenging enzymes, concentration of glutathione, iron binding capacity and ceruloplasmin decreased significantly while the concentration of lipid peroxidation products and NO increased. Hyperdigoxinemia related altered intracellular Ca++ mediated oncogene activation, dolichol induced altered glycoconjugate metabolism and ubiquinone deficiency related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical findings reported could be the cause or the consequence of multiple myeloma. Pathology & Oncology Research, Vol 9, Nr 2, 107-114, 2003

Key words: digoxin; dolichol; ubiquinone; multiple myeloma

Received: Sep 10, 2002; accepted: Apr 14, 2003
Correspondence: Parameswara Achutha KURUP, Metabolic Disorders Research Center, Gouri Sadan, T.C.4/1525, North of Cliff House, Kattu Road, Kowdiar P.O., Trivandrum Kerala , India; Tel: 91-0471-2541607, Fax: 91-0471-2550782; E-mail:

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