ADP-ribose Polymer Metabolism: Implications for Human Nutrition
Research which has led to our current understanding of the relationship between niacin and human health can be segregated into three distinct periods (Figure 1). The first period was concerned with the study of the killer disease, pellagra, and culminated with the discovery by Elvehjem and coworkers of nicotinate and nicotinamide as anti-pellagra factors (1). The second period led to the understanding that nicotinate and nicotinamide were converted within cells to NAD and NADP and that these pyridine nucleotides play a fundamental role in the hydride transfer reactions central to cellular energy metabolism. The third period involves the study of the involvement of NAD as the donor in ADP-ribose transfer reactions. While multiple classes of ADP-ribose transfer reactions occur in cells (2-4), the ADP-ribose metabolism of primary focus in the context described here is the utilization of NAD for the synthesis of polymers of ADP-ribose. As will be described below, the function of ADP-ribose polymer metabolism as a protective response of cells to carcinogen-induced DNA damage leads us to postulate that optimal niacin nutriture may be a preventive factor in carcinogenesis.
KeywordsNicotinate Fractionation Oncol Tryptophan Niacin
Unable to display preview. Download preview PDF.
- 2.Jacobson, M. K. and Jacobson, E. L., Eds. ADP-Ribose Transfer Reactions: Mechanisms and Biological Significance. (1989) Springer-Verlag Publishers, Berlin, Heidelberg, New York.Google Scholar
- 3.Althaus, F.R. and Richter, C., Eds. ADP-Ribosylation of Proteins: Enzymology and Biological Significance. (1987) Springer-Verlag Publishers, Berlin, Heidelberg, New York.Google Scholar
- 4.Jacobson, M.K., Aboul-Ela, N., Cervantes-Laurean, D., Loflin, P.T. and Jacobson, E.L. ADP-Ribose Levels in Animal Cells. (1990) In ADPribosylating Toxins and G-Proteins: Insights into Signal Transduction, J. Moss and M. Vaughan, Eds., American Society for Microbiology, Washington, D.C., pp. 479–492.Google Scholar
- 5.Doll, R., and Peto, R. The Causes of Cancer,: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today. (1981) J. Natl. Cancer Institute 66, 1191–1308.Google Scholar
- 14.Jacobson, E.L., Smith, J.Y., Nunbhakdi, V. and Smith, D.G. ADP-Ribosylation Reactions in Biological Responses to DNA Damage. (1985) In ADPRibosylation of Proteins, F.R. Althaus, H. Hilz and S. Shall, Eds., Springer-Verlag, Berlin, Heidelberg, pp. 277–283.Google Scholar
- 21.Horwitt, M. K., Harvey, C C., Rothwell, W. S., Cutler, J. L., and Haffron, D. (1956) J. Nutr. 60 (Suppl. 1) 43.Google Scholar