Isoprenoid pathway related cascade in multiple myeloma.
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.
Kurup
Ravi kumar
Rk
Department of Neurology, Medical College Hospital, Kerala, India.
Nair
Rekha A
RA
Kurup
Parameswara Achutha
PA
D002118:Calcium / Q000494:pharmacology; D004077:Digoxin / Q000097:blood; D004286:Dolichols / Q000097:blood; D004910:Erythrocyte Membrane / Q000201:enzymology; D005609:Free Radicals / Q000378:metabolism*; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013729:Terpenes / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D014451:Ubiquinone / Q000378:metabolism
D004286:Dolichols; D005609:Free Radicals; D006001:Glycoconjugates; D013729:Terpenes; D014451:Ubiquinone; D014443:Tyrosine; D004077:Digoxin; D014364:Tryptophan; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium