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Nutritional Aspects of Tryptophan Metabolism

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Book cover Targeting the Broadly Pathogenic Kynurenine Pathway

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Abstract

Niacin is biosynthesized from l-tryptophan (Trp). There is a substantial amount of Trp in the body which can be efficiently converted to niacin especially during critical situations. Therefore, it is very important to know the factors affecting the conversion ratio of Trp to niacin. In animal experiments, the conversion ratios decreased with increasing dietary protein levels. Feeding of diets containing unsaturated fatty acids increased the conversion ratio, while feeding of diets with saturated fatty acids did not. In the effects of carbohydrate, the conversion ratio was higher in diets containing starch than in diets containing sucrose. Vitamin B1, vitamin B2, or vitamin B6 deficiency affects the metabolism of Trp to niacin. Mineral deficiency also affects the metabolism of Trp to niacin. With regard to hormones, thyroxin increased the Trp to niacin conversion ratio, while estrone, progesterone, and adrenaline decreased. Certain chemicals can also impact niacin synthesis; alloxane and streptozotocin decreased the conversion ratio, while pyrazinamide, phthalates, valproic acid, and clofibrate increased the ratio. Moderate food restriction greatly decreased the conversion. In human experiments, the urinary excretion ratio of anthranilic acid formation from Trp was calculated to be approximately 0.06 % against Trp intake, kynurenic acid 0.13 %, xanthurenic acid 0.11 %, 3-hydroxyanthranilic acid 0.13 %, and quinolinic acid 0.34 % in basal metabolic level. Supplementing healthy women with up to 5.0 g/day of Trp had no adverse effects. Urinary excretion of 3-hydroxykynurenine is a good surrogate biomarker for excess Trp ingestion.

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Abbreviations

ACMS:

2-Amino-3-carboxymuconate-6-semialdehyde

ACMSD:

2-Amino-3-carboxymuconate-6-semialdehyde decarboxylase

AnA:

Anthranilic acid

3-HA:

3-Hydroxyanthranilic acid

3-HK:

3-Hydroxykynurenine

IDO:

Indoleamine 2,3-dioxygenase

KA:

Kynurenic acid

KYN:

Kynurenine

MNA:

N 1-methylnicotinamide

Nam:

Nicotinamide

NiA:

Nicotinic acid

2-Py:

N 1-methyl-2-pyridone-5-carboxamide

4-Py:

N 1-methyl-4-pyridone-3-carboxamide

PiA:

Picolinic acid

QA:

Quinolinic acid

TDO:

Tryptophan 2,3-dioxygenase

Trp:

l-Tryptophan

XA:

Xanthurenic acid

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Acknowledgements

This investigation was part of the project “Studies on the nutritional evaluation of amino acids and B-group vitamins” (principal investigator, Katsumi Shibata), which was supported by a Research Grant for Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science. This study was also part of the project entitled “Development of an index of metabolic upper intake level instead of tolerable upper intake level of tryptophan for humans” (principal investigator, Katsumi Shibata), which was supported by The International Council on Amino Acid Science (ICAAS) Research Funding.

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  1. Department of Nutrition, School of Human Cultures, The University of Shiga Prefecture, 2500 Hassakacho, Hikone, Shiga, 522-8533, Japan

    Katsumi Shibata Ph.D.

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  1. Katsumi Shibata Ph.D.
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Correspondence to Katsumi Shibata Ph.D. .

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  1. Chairman, Department of Neurosurgery, Wayne State University, Detroit, Michigan, USA

    Sandeep Mittal

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Shibata, K. (2015). Nutritional Aspects of Tryptophan Metabolism. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_3

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