Tryptophan metabolism in vitamin B₆-deficient mice

Abstract

-_ _ -_~--_ _~_ _ _ _ _~~ Vitamin B, deficiency was induced in mice by maintenance for 4 weeks on a vitamin B,-free diet. Tryptophan metabolism was assessed by determining the urinary excretion of tryptophan metabolites, the metabolism of It4Cjtryptophan in vivo and the formation of tryptophan and niacin metabolites by isolated hepatocytes. The vitamin B,-deficient animals excreted more xanthurenic acid and 3-hydroxykynurenine, and less of the niacin metabolites N'-methyl nicotinamide and methyl-2-pyridone-4-carboxamide, than did control animals maintained on the same diet supplemented with 5 mg vitamin B,/kg. After intraperitoneal injection of ['4C]tryptophan, vitamin B,-deficient mice showed lower liberation of I4CO, from Imethylene-'4Cjtryptophan and IU-L4C)tryptophan than did controls, indicating impairment of kynureninase (EC 3 . 7 . 1 .3) activity. There was no difference between the two groups of animals in the metabolism of (ring-2-I4C]tryptophan. Hepatocytes isolated from the vitamin B,-deficient animals formed more 3-hydroxykynurenine and xanthurenic acid than did cells from control animals, but also formed more NADP and free niacin.

Tryptophan-Kynurenine Metabolism and Insulin Resistance in Hepatitis C Patients

“…Formation of XA from 3-HK depends on the vitamin B6 since its active metabolite, pyridoxal 5′-phosphate (P5P), is a cofactor of kynureninase, the enzyme, catalyzing 3-HK metabolism to NAD+ (Figure 1). P5P deficiency shifts 3-HK metabolism from formation of NAD+ to production of XA [30]. It is noteworthy that HCV infection is associated with significantly lowered P5P [31].…”

Neopterin, a Marker of Interferon-Gamma-Inducible Inflammation, Correlates with Pyridoxal-5′-Phosphate, Waist Circumference, HDL-Cholesterol, Insulin Resistance and Mortality Risk in Adult Boston Community Dwellers of Puerto Rican Origin

“…Kynurenine is further metabolized into its derivatives. Since PLP is a cofactor of the key enzymes of post-kynurenine metabolism, PLP deficiency results in increased formation of xanthurenic acid (XA) at the expense of other kynurenine derivatives 27, 28 (Fig. 3).…”

Diabetes and Tryptophan Metabolism

“…Pyridoxal-5-phosphate defi ciency causes downregulation of kynureninase and leads to a shift in tryptophan metabolism from the formation of NAD to excessive production of xanthurenic acid (Bender et al 1990 ). Decreased formation of NAD leads to the inhibition of synthesis and secretion of insulin as well as the death of pancreatic β cells (Okamoto 2003 ).…”