Organ Co-Relationship in Tryptophan Metabolism and Factors That Govern the Biosynthesis of Nicotinamide from Tryptophan

Abstract

The pathway of tryptophan (Trp)-nicotinamide is very important nutritionally because a vitamin nicotinamide is biosynthesized from an amino acid Trp. Until we started studying the factors that affect the Trp-nicotinamide conversion rate, little data existed. Data obtained from TDO (Trp 2,3-dioxygenase)-KO (knock-out) mice have revealed that mice can biosynthesize a necessary amount of nicotinamide from Trp by indoleamine 2,3-dioxygenase (IDO) even when TDO is lacking. It has also been shown that 3-hydroxyanthranilic acid is a key intermediate. Urine upper metabolites such as kynurenic acid and xanthurenic acid originate from non-hepatic tissues but not from the liver. Data obtained from quinolinic acid phosphoribosyltransferase (QPRT)-KO mice indicated that the Trp→quinolinic acid conversion ratio was 6%. Urine quinolinic acid levels and the conversion ratio of Trp to nicotinamide were the same between hetero and wild mice. These findings indicate that QPRT is not the rate-limiting enzyme in the conversion. Thus, the limiting factors in the conversion of Trp to nicotinamide are the amounts of 3-hydroxyanthranilic acid and quinolinic acid in the liver and the activity of liver 3-hydroxyanthranilic acid 3,4-dioxygenase. Studies on factors have shown that conversion of Trp to nicotinamide is increased by adequate intake of good quality protein, and adequate intake of unsaturated fatty acids and starch. However, conversion was decreased by deficient niacin, vitamin B, or vitamin B, excessive intake of protein, saturated fatty acids, or glucose and fructose, or intake of protein with low Trp content, and insufficient mineral intake.

Synthetic analogues of 2-oxo acids discriminate metabolic contribution of the 2-oxoglutarate and 2-oxoadipate dehydrogenases in mammalian cells and tissues

“…7A). It is also known that NAD biosynthesis de novo occurs through the tryptophan transformation into quinolinic acid 78 (QA, Fig. 6), which is alternative to the tryptophan catabolism generating 2-oxoadipate ( Fig.…”

“…6), which is alternative to the tryptophan catabolism generating 2-oxoadipate ( Fig. 6) [78][79][80][81] . It may thus be suggested that the low abundance of OADH is involved in the regulation of the tryptophan fluxes through these alternative catabolic pathways.…”

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications

“…Deficiencies of vitamin B 6 , riboflavin, iron and heme (all essential cofactors for specific enzymes), as well as of vitamin B 1 and Trp itself, slow the reaction rate [18,20]. Overall: (i) a protein-enriched diet (particularly, consumption of foods with high concentrations of leucine, such as maize or sorghum) decreases niacin biosynthesis; (ii) unsaturated fatty acid-enriched diet increases it, while saturated fatty acids do not exert any effect; (iii) the transformation ratio is higher in diets containing starch with respect to sucrose-rich diets; (iv) caloric restriction drastically suppresses biosynthesis [18,21,22,23,24,25,26].…”

Nicotinamide inhibits melanoma in vitro and in vivo

“…It is a precursor of nicotinamide-adenine dinucleotide NAD + [ 1 ] and is known to play an essential role in energy metabolism and to act in several tissues including skin [ 2 ], nervous system [ 3 , 4 ], and muscles [ 5 ]. Its metabolic pathway is related to tryptophan metabolism [ 6 ]. NAM is a key player in the nervous system as well as in skin physiology and immune response control [ 7 , 8 ].…”