Skip to main content
Log in

Isoprenoid pathway related cascade in multiple myeloma

Pathology Oncology Research

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Haupert GT: Sodium pump regulation by endogenous inhibition. Topics in Membrane Transport 34: 345–348, 1989

    Google Scholar 

  2. Cowen PJ, Wood AJ: Biological markers of depression. Psychol Med 21:831–836, 1991

    PubMed  CAS  Google Scholar 

  3. Kramer HJ, Meyer Lehnert H et al: Endogenous natriuretics and ouabain like factors and their roles. Am J Hypertens 1:81–89, 1991

    Google Scholar 

  4. Tamura H, Shimoyama S, Sunaga Y: Digoxin like immunoreactive substance in urine of patients with mucocutaneous lymphnode syndrome. Angiology 10: 856–865, 1992

    Article  Google Scholar 

  5. Rhee HM: Parallelism between transport inhibition and L1210 cell growth by ouabain. Adv Exp Med Biol 22: 727–734, 1988

    Google Scholar 

  6. Buchwald H: Cholesterol inhibition, cancer and chemotherapy. Lancet 339: 1154–1156, 1992

    Article  PubMed  CAS  Google Scholar 

  7. Barinaga M. From Bench Top to Bedside. Science 278: 1036–1038, 1997

    Article  PubMed  CAS  Google Scholar 

  8. Jacob RA. Nutrition, health and antioxidants. INFORM 5:1271–1275, 1994

    Google Scholar 

  9. Linstinsky JL, Siegal GP, Listinsky CM. Alpha-L-Fucose a potentially critical molecule in pathologic process including neoplasia. Am J Clin Pathol 110: 425–440, 1998

    Google Scholar 

  10. Teoh G, Anderson KC. Interaction of tumor and host cells with adhesion and extracellular matrix molecules in the development of multiple myeloma. Hematol Oncol Clin N Amer 11: 27–39, 1997

    Article  CAS  Google Scholar 

  11. Hisaka A, Kasamatu, Takenaga N: Absorption of a novel prodrug DOPA. Drug Metab Disp 18: 621–625, 1990

    CAS  Google Scholar 

  12. Saito K, Crowley JS, Markey S, Heyes MP: A mechanism for increased quinolinic acid formation following acute systemic immune stimulation. J Biol Chem 268: 15496–503, 1993

    PubMed  CAS  Google Scholar 

  13. Felton D, Cohen N, Ader R: Psychoneuroimmunology. Academic Press, New York 1991

    Google Scholar 

  14. Arun P, Ravikumar 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 107: 231–238, 1998b

    CAS  Google Scholar 

  15. Rao AV, Ramakrishnan S: Estimation of HMG CoA reductase activity. Clin Chem 21:1523–1528, 1975

    PubMed  CAS  Google Scholar 

  16. Wallach DFH, Kamath VB. Methods Enzymol 8. Academic Press, New York, 1966.

    Google Scholar 

  17. Arun P, Ravikumar A, Leelamma S, Kurup PA: Identification and estimation of endogenous EDLF in biological fluids and tissues by TLC and HPLC. Ind J Biochem Biophys 35: 308–312, 1998a

    CAS  Google Scholar 

  18. 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 140:315–319, 1984

    Article  PubMed  CAS  Google Scholar 

  19. Bloxam DL, Warren WH. Error in the determination of tryptophan by the method of Denkala and Dewey. A revised procedure. Anal Biochem 60: 621–625, 1974

    Article  PubMed  CAS  Google Scholar 

  20. Wong PWK, O’Flynn ME, Inouye R. Flourimetric method for Tyrosine. Clin Chem 10: 1098–1100, 1964

    PubMed  CAS  Google Scholar 

  21. Curzon G, Green AR. Rapid method for the determination of 5-hydroxy tryptophan and 5-hydroxy indoleacetic acid in certain regions of rat brain. Br J Pharmacol 39: 653–655, 1979

    Google Scholar 

  22. Well-Malherbe R. Methods of Biochemical Analysis. Inter Science, New York, 1971

    Google Scholar 

  23. Manoj AJ, Kurup PA. Changes in the glycosaminoglycans and glycoproteins in the rat brain during protein calorie malnutrition. Clin Biochem Nutr 25: 149–157, 1998

    Google Scholar 

  24. Lowenstein JM. Methods in Enzymology. Academic Press, New York, 1969

    Google Scholar 

  25. Kakkar P, Das B, Viswanathan PN: A modified spectrophotometric assay of SOD. Ind J Biochem Biophys 21: 130, 1984

    CAS  Google Scholar 

  26. Maehly AC, Chance B: The assay of catalase and peroxidase. Methods Biochemical Analysis 2: 357, 1954

    Article  Google Scholar 

  27. Paglia DE, Valentine WN. Studies on quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Lab Clin Med 70: 158, 1967

    PubMed  CAS  Google Scholar 

  28. Horn HD, Burns FH: Methods of Enzymatic Analysis. Academic Press, New York 1978

    Google Scholar 

  29. Brien PJO. Estimation of conjugated dienes and hydroperoxide. Can J Biochem 47: 485, 1969

    Article  Google Scholar 

  30. Beutler E, Duran O, Kelley BM Modified procedure for the estimation of reduced glutathione. J Lab Clin Med 61: 882, 1963

    PubMed  CAS  Google Scholar 

  31. Colin G, Rammel R, Cunlifee B, Keiboom AJ. Determination of alpha tocopherol in biological specimens by high performance liquid chromatography. J Liq Chromatogr 6: 1123, 1983

    Article  Google Scholar 

  32. Gabor G, Allon N: Spectrofluorometric method for NO determination. Anal Biochem 220: 16, 1994

    Article  PubMed  CAS  Google Scholar 

  33. Wootton IDP: Estimation of iron binding capacity. Microanal Med Biochem 4: 124, 1964

    Google Scholar 

  34. Henry RJ, Chiamori N, Jacobs SL, Segalov M. Estimation of ceruloplasmin. Proc Soc Exp Biol Med 104: 620, 1960

    CAS  Google Scholar 

  35. Falholt K, Lund B, Fatholt W Estimation of free fatty acids. Clin Chem Acta 46: 105, 1973

    Article  CAS  Google Scholar 

  36. Haga H. Effects of dietary magnesium supplementation on diurnal variation of BP and plasma Na + K+ ATPase activity in essential hypertension. Jap Heart J 33: 785–798, 1992

    PubMed  CAS  Google Scholar 

  37. Feinman RM, Sawyer J, Hardin J, Tricot G: Cytogenetics and molecular genetics in multiple myeloma. Hemat Oncol Clin N Am 11: 1–21, 1997

    Article  CAS  Google Scholar 

  38. Ravikumar A., Deepadevi KV, Arun P et al: Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders. Neurol Ind 48: 231–238, 2001

    Google Scholar 

  39. Irwin M, Lacher U, Caldwell C. Depression and decreased natural killer cell cytotoxicity. A longitudinal study of depressed patients and control subjects. Psychol Med 22:1045–1050, 1992

    Article  PubMed  CAS  Google Scholar 

  40. Lauder JM. Neurotransmitters as growth regulatory signals: role of receptors and second messengers. Trends Neurosci 16: 233–238, 1993

    Article  PubMed  CAS  Google Scholar 

  41. Greenamyre JT, Poter RHP. Anatomy and Physiology of glutamate in CNS. Neurol 44, S8: S7-S13, 1994

    Google Scholar 

  42. Monia BP, Ecker J, Crooks ST. Ubiquitination Enzymes. Biotechnol 8:209–215, 1990

    Article  CAS  Google Scholar 

  43. Ploegh HL. Viral strategies for immune evasion. Science 280:248–253, 1998

    Article  PubMed  CAS  Google Scholar 

  44. Rettig MB, Ma HJ, Vesico RA et al.: Kaposi’s sarcoma associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients. Science 276:1851–1857, 1997

    Article  PubMed  CAS  Google Scholar 

  45. Green DR, Reed JC: Mitochondria and apoptosis. Science 281:1309–1316, 1998

    Article  PubMed  CAS  Google Scholar 

  46. Mukhopadhyay CK, Attieh ZK, Fox PL: Role of ceruloplasmin in cellular iron uptake. Science 279: 714–717, 1998

    Article  PubMed  CAS  Google Scholar 

  47. Finkel TH: Tcell development and transmembrane signalling. Changing biological responses through a unchanging receptor. Immunol Today 12: 79–86, 1991

    Article  PubMed  CAS  Google Scholar 

  48. Barut BA, Zon LI, Cochran MK. Role of interleukin - 6 in the growth of myeloma derived cell lines. Leukaem Res 16: 951, 1992

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Parameswara Achutha Kurup.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kurup, R.k., Nair, R.A. & Kurup, P.A. Isoprenoid pathway related cascade in multiple myeloma. Pathol. Oncol. Res. 9, 107–114 (2003). https://doi.org/10.1007/BF03033754

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033754

Keywords

Navigation