Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-06T02:06:57.410Z Has data issue: false hasContentIssue false
  • English
  • Français

Probable mechanisms of regulation of the utilization of dietary tryptophan, nicotinamide and nicotinic acid as precursors of nicotinamide nucleotides in the rat

Published online by Cambridge University Press:  09 March 2007

David A. Bender ,
Bahieldin I. Magboul  and
David Wynick
David A. Bender
Affiliation:
Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, London WIP 7PN
Bahieldin I. Magboul
Affiliation:
Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, London WIP 7PN
David Wynick
Affiliation:
Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, London WIP 7PN
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

1. The regulation of the utilization of dietary tryptophan, nicotinamide and nicotinic acid as precursors of the nicotinamide nucleotides has been studied in groups of rats fed on diets providing only one of these precursors at a time, in amounts adequate to meet their requirements for nucleotide synthesis.

2. The concentration of nicotinamide nucleotides in the liver of rats receiving a high-tryptophan diet was 56% higher than in animals fed on a diet providing a minimum amount of tryptophan, together with nicotinic acid or nicotinamide. The excretion of N1-methyl nicotinamidc was three times higher in the tryptophan-fed animals than in the other two groups.

3. The concentration of quinolinic acid in the liver was significantly higher in animals receiving the high-tryptophan diet than in the other two groups; that of nicotinic acid was highest in those animals receiving the nicotinic-acid-containing diet. The concentration of nicotinamide was highest in the livers of those animals receiving the high-tryptophan diet, and lowest in those receiving the nicotinic-acid-contaning diet.

4. The values of the Michaelis constant Km of nicotinamide deamidase (nicotinamide amidohydrolase. EC 3.5,1,19) and nicotinamide phosphoribosylltransferase (nicotinamide nucleotide: pyrophosphate phosphoribosyltransferase, EC 2.4.2.12) were approximately equal, and approximately one-tenth of the concentration of nicotinamide was in the liver. This suggests that both these enzymes normally function at their maximum rate, and a change in the availability of nicotinamide would not affect the rate of its incorporation into nucleotides.

5. The maximum rate of reaction (Vmax) of nicotinamide deamidase was twice that of nicotinamide phosphoribosyltransferase; this suggests that unless compartmental or other factors are involved, the major route of nicotinamide utilization will be by way of deamidation.

6. The Km of nicotinate phosphoribosyltransferase (nicotinate nucleotide: pyrophosphate phosphoribosyltransferase, EC 2.4.2.11) was less than twice the concentration of nicotinic acid in the liver, so that a change in the availability of nicotinic acid might be expected to lead to a small change in the rate of its utilization.

7. The Km of quinolinate phosphoribosyltransferase (nicotinate nucleotide: pyrophosphate phosphoribosyltransferase (carboxylating) EC 2.4.2.19) was approximately 100 times greater than the concentration of quinolinic acid in the liver, so that any change in the availability of quinolinic acid would be expected to lead to a considerable change in the rate of its utilization. The Vmax of quinolinate phosphoribosyltransferase was relatively low, so that under conditions of high tryptophan flux, some accumulation of quinolinic acid might be expected. This was observed in animals receiving the high-tryptophan diet.

8. It is concluded that it is unlikely that the utilization of quinolinic acid, arising from tryptophan. for the synthesis of nicotinamide nucleotides is regulated, but that control over tissue concentrations of nucleotides is achieved by hydrolysis of NAD to nicotinamide. Incorporation of nicotinamide into nucleotides seems to be strictly limited by the activity of the enzymes involved.

Type
Papers on General Nutrition
Information
British Journal of Nutrition , Volume 48 , Issue 1 , July 1982 , pp. 119 - 127
Copyright
Copyright © The Nutrition Society 1982

References

REFERENCES

Bender, D. A. (1980 a). Biochem. Pharmac. 29, 707.CrossRefGoogle Scholar
Bender, D. A. (1980 b). Biochem. Pharmac. 29, 2099.CrossRefGoogle Scholar
Carlson, L. A. (1966). Clinica Chim. Acta 13, 349.CrossRefGoogle Scholar
Carpenter, K. J. & Kodicek, E. (1950). Biochem. J. 46, 421.CrossRefGoogle Scholar
Carter, E. G., Hurrell, R. F. & Carpenter, K. J. (1977). Proc. Nutr. Soc. 36, 107A.Google Scholar
Delabar, U. & Siess, M. (1979). Bas. Res. Cardiol. 74, 571.CrossRefGoogle Scholar
Gadd, R. E. A. & Johnson, W. J. (1974). Int. J. Biochem. 5, 397.CrossRefGoogle Scholar
Green, S. & Dobrzansky, A. (1967). Cancer Res. 27, 261.Google Scholar
Greengard, O. & Feigelson, P. (1961). J. biol. Chem. 236, 158.CrossRefGoogle Scholar
Grunicke, H., Keller, H. J., Liersch, M. & Benaguid, A. (1974). Adv. Enz. Reg. 12, 397.CrossRefGoogle Scholar
Horwitt, M. K., Harvey, C. C., Rothwell, W. S., Cutler, J. L. & Haffron, D. (1956). J. Nutr 26, suppl. 1, 1.CrossRefGoogle Scholar
Kaplan, N. O., Colowick, S. P. & Barnes, C. C. (1951). J. biol. Chem. 191, 461.CrossRefGoogle Scholar
Lardy, H. A. (1971). Am. J. Clin. Nutr. 24, 764.CrossRefGoogle Scholar
Lowry, O. H., Passoneau, J. V. & Rock, H. K. (1961). J. biol. Chem. 236, 2756.CrossRefGoogle Scholar
McDaniel, H. G., Boshell, B. R. & Reddy, W. J. (1973). Diabetes 22, 713.CrossRefGoogle Scholar
National Research Council (1962). Nutrient Requirements of Laboratory Animals. Washington, DC: National Research Council.Google Scholar
Nishizuka, Y. & Hayaishi, O. (1963). J. biol. Chem. 238, 3369.CrossRefGoogle Scholar
Petrack, B., Greengard, P., Craston, A. & Kalinsky, H. J. (1963). Biochem. biophys. Res. Commun. 13, 472.CrossRefGoogle Scholar
Petrack, B., Greengard, P., Craston, A. & Sheppey, F. (1965). J. biol. Chem. 240, 1725.CrossRefGoogle Scholar
Pinder, S., Clark, J. B. & Greenbaum, A. L. (1971). Meth. Enzym. 18B, 20.CrossRefGoogle Scholar
Schimke, R. T., Sweeney, E. W. & Berlin, C. M. (1965 a). J. biol. Chem. 240, 322.CrossRefGoogle Scholar
Schimke, R. T., Sweeney, E. W. & Berlin, C. M. (1965 b). J. biol. Chem. 240, 4609.CrossRefGoogle Scholar
Shaikh, B., Huang, S.-K. S. & Pontzer, N. J. (1980). Chem-Biol. Interactions 30, 253.CrossRefGoogle Scholar
Smith, S. A., Marston, F. A. O., Dickson, A. J. & Pogson, C. I. (1979). Biochem. Pharmac. 28, 1645.CrossRefGoogle Scholar
Wagner, C. (1964). Biochem. Biophys. Res. Commun. 17, 668.CrossRefGoogle Scholar
Wertz, A. W., Lojkin, M. I., Bouchard, B. S. & Derby, M. B. (1958). J. Nutr. 64, 339.CrossRefGoogle Scholar