FNS> Vol.5 No.14, August 2014

Dodecylamine Derivative of Hydroxocobalamin Acts as a Potent Inhibitor of Cobalamin-Dependent Methionine Synthase in Mammalian Cultured COS-7 Cells

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We evaluated whether the dodecylamine derivative of hydroxocobalamin acts as a potent inhibitor of cobalamin-dependent enzymes in an African green monkey kidney cell, COS-7. When the dodecylamine derivative (1.0 μmol/L) did not show any cytotoxicity in the cultured cells, the derivative could not affect methylmalonyl-CoA mutase (holo-enzyme) activity, but significantly inhibit methionine synthase (holo-enzyme) activity in the cell homogenates of COS-7 grown in 1.0 μmol/L hydroxocobalamin-supplemented medium. An immunoblot analysis indicated that the dodecylamine derivative could not decrease the protein level of methionine synthase, but significantly inhibit the enzyme activity.

Cite this paper

Bito, T. , Yasui, M. , Iwaki, T. , Yabuta, Y. , Ichiyanagi, T. , Yamaji, R. , Nakano, Y. , Inui, H. and Watanabe, F. (2014) Dodecylamine Derivative of Hydroxocobalamin Acts as a Potent Inhibitor of Cobalamin-Dependent Methionine Synthase in Mammalian Cultured COS-7 Cells. Food and Nutrition Sciences, 5, 1318-1325. doi: 10.4236/fns.2014.514143.


[1] Alpers, D.H. and Russell-Jones, G.I. (1999) Intrinsic Factor, Haptocorrin, and Their Receptors. In: Banerjee, R., Ed., Chemistry and Biochemistry of Vitamin B12, John Wiley & Sons, New York, 411-439.
[2] Rothenberg, S.P., Quadros, E.V. and Regec, A. (1999) Transcobalamin II. In: Banerjee, R., Ed., Chemistry and Biochemistry of Vitamin B12, John Wiley & Sons, New York, 441-473.
[3] Barnerjee, R. (2001) Radical Peregrinations Catalyzed by Coenzyme B12-Dependent Enzymes. Biochemistry, 40, 6191-6198. http://dx.doi.org/10.1021/bi0104423
[4] Toohey, J.I. (2006) Vitamin B12 and Methionine Synthesis: A Critical Review. Is Nature’s Most Beautiful Cofactor Misunderstood? BioFactors, 26, 45-57.
[5] Institute of Medicine (1998) Vitamin B12. In: Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, Institute of Medicine, National Academy Press, Washington DC, 306-356.
[6] O’Leary, F. and Samman, S. (2010) Vitamin B12 in Health and Disease. Nutrients, 2, 299-316.
[7] Toyoshima, S., Watanabe, F., Saido, H., Pezacka, E., Jacobsen, D.W., Miyatake, K. and Nakano, Y. (1996) Accumulation of Methylmalonic Acid Caused by Vitamin B12-Deficiency Disrupts Normal Cellular Metabolism in Rat Liver. British Journal of Nutrition, 75, 929-938.
[8] Matthews, J.H. (1997) Cyanocobalamin [c-Lactam] Inhibits Vitamin B12 and Causes Cytotoxicity in HL60 Cells: Methionine Protects Cells Completely. Blood, 89, 4600-4607.
[9] Stabler, S.P., Brass, E.P., Marcell, P.D. and Allen, R.H. (1991) Inhibition of Cobalamin-Dependent Enzymes by Cobalamin Analogues in Rats. Journal of Clinical Investigation, 87, 1422-1430.
[10] McEwan, J.F., Veitch, H.S. and Russell-Jones, G.J. (1999) Synthesis and Biological Activity of Ribose-5’-Carbamate Derivatives of Vitamin B12. Bioconjugate Chemistry, 10, 1131-1136.
[11] Saido, H., Watanabe, F., Tamura, Y., Nanai, Y. and Nakano, Y. (1993) Effects of Vitamin B12 Analogues with Alternation in the Side Chains of the Corrin Ring on Urinary Methylmalonate Excreation in Vitamin B12-Deficient Rats. Bioscience, Biotechnology, and Biochemistry, 57, 607-610.
[12] Miyamoto, E., Tanioka, Y., Nishizawa-Yokoi, A., Yabuta, Y., Ohnishi, K., Nisono, H., Shigeoka, S., Nakano, Y. and Watanabe, F. (2010) Characterization of Methylmalonyl-CoA Mutase Involved in the Propionate Photoassimilation of Euglena gracilis Z. Archives of Microbiology, 192, 437-446.
[13] Tanioka, Y., Yabuta, Y., Yamaji, R., Shigeoka, S., Nakano, Y., Watanabe, F. and Inui, H. (2009) Occurrence of Pseudovitamin B12 and Its Possible Function as the Cofactor of Cobalamin-Dependent Methionine Synthase in a Cyanobacterium Synechocysitis sp. PCC6803. Journal of Nutritional Science and Vitaminology, 55, 518-521.
[14] Chen, Z., Chakraborty, S. and Banerjee, B. (1995) Demonstration That Mammalian Methionine Synthases Are Predominantly Cobalamin-Loaded. Journal of Biological Chemistry, 270, 19246-19249.
[15] Waly, W., Olteanu, H., Banerjee, R., Choi, S.W., Mason, J.B., Parker, B.S., Sukumar, S., Shim, S., Sharma, A., Benzecry, J.M., Power-Charnitsky, V.A. and Deth, R.C. (2004) Activation of Methionine Synthase by Insulin-Like Growth Factor-1 and Dopamine: A Target for Neurodevelopmental Toxins and Thimerosal. Molecular Psychiatry, 9, 358-370.

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