Office: 843-792-0013
Lab: 843-792-1277
Fax: 843-792-4850
Email: krupenkn@musc.edu
BSB-733D

Research Interests

My research area could be broadly defined as Folate and methyl group metabolism.  Methyl transfer reactions are extremely important to cellular biochemistry. Dietary deficiency of labile methyl groups is the only nutrient deficiency known to be carcinogenic in itself. However, only a few types of methyl donors are used in the cell, and S-adenosylmethionine (SAM) is the most common of them. SAM is second only to ATP in the variety of reactions for which it serves a cofactor. The second most commonly used methyl donor is various forms of folates. Methyl groups from the folate pool can be used to re-methylate homocysteine to methionine and, thus, restore the methylating potential of the cell. It is believed that some of the effects of folate deficiency in higher animals results from the disruption of methyl group metabolism.  There are more than 120 different SAM-dependent methyltransferases present in small amounts in the cell, each catalyzing the synthesis of an essential product. Activity of these enzymes is regulated by the SAM/SAH ratio. My research is focused on a unique member of the methyltransferase family - glycine N-methyltransferase (GNMT). This enzyme is an abundant protein in mammalian liver cytosol (1-3% of the soluble protein), it is less sensitive to the backfeed inhibition by the product S-adenosylhomocysteine (SAH) than all other methyltransferases, and it does not yield a biologically active compound necessary for cellular metabolism. Besides, GNMT is a major folate-binding protein in mammalian liver cytosol. This protein is believed to function as a regulatory switch in methionine conservation/transsulfuration pathway to maintain SAM/SAH ratio adequate for the cell. Additional gene-regulatory functions have been suggested for this protein. Along with the unique properties, GNMT has a molecular structure drastically different from the structures of other methyltransferases. Therefore, one of the aims of my research is a structure-functional characterization of GNMT including the study of enzyme oligomerization and elucidation of the structures and mechanisms involved in folate binding and inhibition of the enzyme activity. Another point of interest is the study of nuclear localization and transport of GNMT, its binding targets and determination of the possible biological function of GNMT in the nucleus. Studies of tissue expression of the enzyme and its regulation in different physiological and pathological conditions will help to improve our understanding of the role of GNMT in folate and methyl group metabolism.

Selected Publications

• Krupenko, N.I., Wagner, C. (1997) Transport of rat liver glycine N-methyltransferase into rat liver nuclei. J. Biol. Chem. 272:27140-27146.
• Krupenko, S.A., Krupenko, N.I., Danzo, B.J. (1994) Interaction of sex hormone-binding globulin with plasma membranes from the rat epididymis and other tissues. J. Steroid Biochem. Molec. Biol. 51:115-124.