Increased Conversion of Tryptophan to Nicotinamide in Rats by Dietary Valproate

Organ Correlation with Tryptophan Metabolism Obtained by Analyses of TDO-KO and QPRT-KO Mice

“…We have previously reported that the conversion percentage of niacin from Trp is around 2% in molar ratio, the rate-limiting enzyme is quinolinic acid phosphoribosyltransferase (QPRT), and this pathway mainly exists in the liver, while nonhepatic tissues are not associated with this conversion pathway. 1–20 However, our recent findings 21,22 have revealed that the latter is incorrect.…”

“…Next, we examined the enzyme that controls the formation of niacin from Trp in the liver. 2–5,10–12,15,16,18,19,23 The relationship between tryptophan 2,3-dioxygenase (TDO) and urine Nam and its catabolites was not significant. The relationship between 3-hydroxyanthranilic acid 3,4-dioxygenase (3-HADO) and urine total amount of Nam and its catabolites was significant ( P = 0.040).…”

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“… 155 Shibata et al 155 demonstrated an increase in nicotinamide formation due to increased tryptophan breakdown induced by valproate, in rats. 155 Valproate has a further action in displacing tryptophan from plasma albumin; 156 this increases central kynurenic acid and tryptophan levels. 156 Valproate also increases liver NAD concentration.…”

“… 156 Valproate also increases liver NAD concentration. 155 Other short-chain fatty acids, 3-hydroxybutyrate, acetoacetate, and dietary fats, similar to valproate also increase central tryptophan levels 157 – displacing it from plasma albumin 147 and increasing tryptophan breakdown, to form more nicotinamide.…”

The Effects of Glycine, L-Threonine, and L-Cystine Supplementation to a 9% Casein Diet on the Conversions of L-Tryptophan to Nicotinamide and to Serotonin in Rats

“…Male rats of the Wistar strain (7 wk old) were obtained from CLEA Japan, Inc. (Tokyo, Japan) and immediately placed in individual CT-10 metabolic cages (CLEA Japan). The rats were initially fed ad libitum for 7 d with a 20% casein diet (22) to accustom them to these conditions. They were then divided into five groups and ad libitum fed a low-protein (9% casein) diet ([1] control), or one of the low protein diets supplemented with following amino acids: [2] Gly, l-Thr, and l-cystine, [3] l-Thr and l-cystine, [4] Gly and l-cystine, and [5] Gly and l-Thr.…”