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.
References
Haupert GT: Sodium pump regulation by endogenous inhibition. Topics in Membrane Transport 34: 345–348, 1989
Cowen PJ, Wood AJ: Biological markers of depression. Psychol Med 21:831–836, 1991
Kramer HJ, Meyer Lehnert H et al: Endogenous natriuretics and ouabain like factors and their roles. Am J Hypertens 1:81–89, 1991
Tamura H, Shimoyama S, Sunaga Y: Digoxin like immunoreactive substance in urine of patients with mucocutaneous lymphnode syndrome. Angiology 10: 856–865, 1992
Rhee HM: Parallelism between transport inhibition and L1210 cell growth by ouabain. Adv Exp Med Biol 22: 727–734, 1988
Buchwald H: Cholesterol inhibition, cancer and chemotherapy. Lancet 339: 1154–1156, 1992
Barinaga M. From Bench Top to Bedside. Science 278: 1036–1038, 1997
Jacob RA. Nutrition, health and antioxidants. INFORM 5:1271–1275, 1994
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
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
Hisaka A, Kasamatu, Takenaga N: Absorption of a novel prodrug DOPA. Drug Metab Disp 18: 621–625, 1990
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
Felton D, Cohen N, Ader R: Psychoneuroimmunology. Academic Press, New York 1991
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
Rao AV, Ramakrishnan S: Estimation of HMG CoA reductase activity. Clin Chem 21:1523–1528, 1975
Wallach DFH, Kamath VB. Methods Enzymol 8. Academic Press, New York, 1966.
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
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
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
Wong PWK, O’Flynn ME, Inouye R. Flourimetric method for Tyrosine. Clin Chem 10: 1098–1100, 1964
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
Well-Malherbe R. Methods of Biochemical Analysis. Inter Science, New York, 1971
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
Lowenstein JM. Methods in Enzymology. Academic Press, New York, 1969
Kakkar P, Das B, Viswanathan PN: A modified spectrophotometric assay of SOD. Ind J Biochem Biophys 21: 130, 1984
Maehly AC, Chance B: The assay of catalase and peroxidase. Methods Biochemical Analysis 2: 357, 1954
Paglia DE, Valentine WN. Studies on quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Lab Clin Med 70: 158, 1967
Horn HD, Burns FH: Methods of Enzymatic Analysis. Academic Press, New York 1978
Brien PJO. Estimation of conjugated dienes and hydroperoxide. Can J Biochem 47: 485, 1969
Beutler E, Duran O, Kelley BM Modified procedure for the estimation of reduced glutathione. J Lab Clin Med 61: 882, 1963
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
Gabor G, Allon N: Spectrofluorometric method for NO determination. Anal Biochem 220: 16, 1994
Wootton IDP: Estimation of iron binding capacity. Microanal Med Biochem 4: 124, 1964
Henry RJ, Chiamori N, Jacobs SL, Segalov M. Estimation of ceruloplasmin. Proc Soc Exp Biol Med 104: 620, 1960
Falholt K, Lund B, Fatholt W Estimation of free fatty acids. Clin Chem Acta 46: 105, 1973
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
Feinman RM, Sawyer J, Hardin J, Tricot G: Cytogenetics and molecular genetics in multiple myeloma. Hemat Oncol Clin N Am 11: 1–21, 1997
Ravikumar A., Deepadevi KV, Arun P et al: Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders. Neurol Ind 48: 231–238, 2001
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
Lauder JM. Neurotransmitters as growth regulatory signals: role of receptors and second messengers. Trends Neurosci 16: 233–238, 1993
Greenamyre JT, Poter RHP. Anatomy and Physiology of glutamate in CNS. Neurol 44, S8: S7-S13, 1994
Monia BP, Ecker J, Crooks ST. Ubiquitination Enzymes. Biotechnol 8:209–215, 1990
Ploegh HL. Viral strategies for immune evasion. Science 280:248–253, 1998
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
Green DR, Reed JC: Mitochondria and apoptosis. Science 281:1309–1316, 1998
Mukhopadhyay CK, Attieh ZK, Fox PL: Role of ceruloplasmin in cellular iron uptake. Science 279: 714–717, 1998
Finkel TH: Tcell development and transmembrane signalling. Changing biological responses through a unchanging receptor. Immunol Today 12: 79–86, 1991
Barut BA, Zon LI, Cochran MK. Role of interleukin - 6 in the growth of myeloma derived cell lines. Leukaem Res 16: 951, 1992
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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
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DOI: https://doi.org/10.1007/BF03033754