Tryptophan-Niacin Relationships in Man Studies with Diets Deficient in Riboflavin and Niacin, Together with Observations on the Excretion of Nitrogen and Niacin Metabolites

Horwitt, M. K.; Harvey, C. C.; Rothwell, Walter S.; Cutler, Jeffrey L.; Haffron, D.

doi:10.1093/jn/60.suppl_1.1

Cited by 107 publications

(29 citation statements)

References 26 publications

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“…In man the ability to utilize tryptophan as a source of nicotinamide nucleotides varies considerably from one individual to another. The widely-quoted equivalence of 60 mg tryptophan : 1 mg nicotinamide was suggested by Horwitt et al (1956) to ensure an adequate excess to cover the wide range observed in their study. Changes in hormonal status that affect tryptophan metabolism, such as pregancy, also affect the apparent equivalence of tryptophan and niacin (Wertz ei al.…”

Section: Discussionmentioning

confidence: 99%

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

1982

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I . 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 W-methyl nicotinamide 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-containing diet.4. The values of the Michaelis constant K , of nicotinamide deamidase (nicotinamide ainidohydrolase, EC 3 . 5 . I .19) and nicotinamide phosphoribosyltransferase (nicotinamide nucleotide: pyrophosphate phosphoribosyltransferase, EC2.4.2.12) 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 K , 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 K, of quinolinate phosphoribosyltransferase (nicotinate nucleotide : pyrophosphate phosphoribosyltransferase (carboxylating) EC 2 . 4 . 2 . 1 9 ) 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 V,,, 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 conce...

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Section: Discussionmentioning

confidence: 99%

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

1982

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“…The patient who lost weight had frequent intercurrent illnesses and progression of his malignant disease. The vitamin and mineral supplements provided quantities equal to or in excess of recommended values and exceeded the amounts used by Hills and co-workers (5) and Horwitt and associates (6). Two (V.T., C.R.)…”

Section: Discussionmentioning

confidence: 83%

“…All counts were corrected for background radioactivity and physical decay. The counts per minute per milliliter of plasma 6 Performed by Dr. John L. Fahey. 7Determined by Dr. John Sieri.…”

mentioning

confidence: 99%

The Rapid Induction of Human Riboflavin Deficiency with Galactoflavin *

Lane¹,

Alfrey²,

Mengel³

et al. 1964

J. Clin. Invest.

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Signs of riboflavin deficiency require many months to develop in patients placed on riboflavinrestricted diets (1-6). The demonstrations that riboflavin deficiency induced by dietary restriction or riboflavin antagonists resulted in regression of rodent tumors (7-13) prompted several efforts in this laboratory to produce riboflavin deficiency in patients with neoplastic disease (14, 15). Riboflavin antagonists were used in these studies with the objective of producing the deficiency state rapidly, since a regimen requiring many months of dietary restriction would not lend itself to therapeutic evaluation in patients with metastatic cancer. These earlier investigations did not result in the production of clinical evidences of riboflavin deficiency or in objective demonstrations of tumor regression. The administered riboflavin antagonists, selected on the basis of their effectiveness in rats, were shown to be metabolized differently in man. The most active of these agents against rat tumors, 6,7-dimethyl-9-(2'-acetoxyethyl) -isoalloxazine, was rapidly and almost completely hydrolyzed in man, although a significant amount of the absorbed drug was excreted unchanged by rats. With the objective of producing human riboflavin deficiency, an analog was sought that would be an effective riboflavin antagonist in rodents and would be metabolized similarly in rodents and in man.The present paper describes studies with 1O-Ddulcityl -7,8-dimethyl-isoalloxazine, galactoflavin,

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“…Aside from the differ ences in tryptophan requirement between growing and mature indi viduals, the problem of protein balance is introduced. In humans sub jected to low-niacin diets, urinary nitrogen excretion did not reach a steady state for three months after the introduction of a pellagragenic diet, which was, of necessity, low in protein (67). Direct determination of tryptophan-niacin equivalence ratios in mature subjects is probably best performed by measuring urinary A^-methylnicotinamide excretion at near deficiency levels of niacin and niacin-equivalent supplementation.…”

Section: Niacinmentioning

confidence: 99%