UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

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

Bender, DA; Magboul, BI; Wynick, D; (1982) Probable mechanisms of regulation of the utilization of dietary tryptophan, nicotinamide and nicotinic acid as precursors of nicotinamide nucleotides in the rat. British Journal of Nutrition , 48 (1) 119 - 27. 10.1079/BJN19820094. Green open access

[img]
Preview
PDF
download.pdf
Available under License : See the attached licence file.

Download (1MB)

Abstract

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: Article
Title: Probable mechanisms of regulation of the utilization of dietary tryptophan, nicotinamide and nicotinic acid as precursors of nicotinamide nucleotides in the rat
Open access status: An open access version is available from UCL Discovery
DOI: 10.1079/BJN19820094
Publisher version: http://dx.doi.org/10.1079/BJN19820094
Language: English
Additional information: © 1982 Cambridge University Press
Keywords: Animals, Diet, Liver, metabolism, Male, NAD, biosynthesis, Niacin, Niacinamide, Nicotinamidase, Nicotinic Acids, Pentosyltransferases, Quinolinic Acids, Rats, Inbred Strains, Tryptophan
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/137526
Downloads since deposit
204Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item