Metabolite Profile Analysis Reveals Functional Effects of 28-Day Vitamin B-6 Restriction on One-Carbon Metabolism and Tryptophan Catabolic Pathways in Healthy Men and Women

Abstract

Suboptimal vitamin B-6 status, as reflected by low plasma pyridoxal 5'-phosphate (PLP) concentration, is associated with increased risk of vascular disease. PLP plays many roles, including in one-carbon metabolism for the acquisition and transfer of carbon units and in the transsulfuration pathway. PLP also serves as a coenzyme in the catabolism of tryptophan. We hypothesize that the pattern of these metabolites can provide information reflecting the functional impact of marginal vitamin B-6 deficiency. We report here the concentration of major constituents of one-carbon metabolic processes and the tryptophan catabolic pathway in plasma from 23 healthy men and women before and after a 28-d controlled dietary vitamin B-6 restriction (<0.35 mg/d). liquid chromatography-tandem mass spectrometry analysis of the compounds relevant to one-carbon metabolism showed that vitamin B-6 restriction yielded increased cystathionine (53% pre- and 76% postprandial; P < 0.0001) and serine (12% preprandial; P < 0.05), and lower creatine (40% pre- and postprandial; P < 0.0001), creatinine (9% postprandial; P < 0.05), and dimethylglycine (16% postprandial; P < 0.05) relative to the vitamin B-6-adequate state. In the tryptophan pathway, vitamin B-6 restriction yielded lower kynurenic acid (22% pre- and 20% postprandial; P < 0.01) and higher 3-hydroxykynurenine (39% pre- and 34% postprandial; P < 0.01). Multivariate ANOVA analysis showed a significant global effect of vitamin B-6 restriction and multilevel partial least squares-discriminant analysis supported this conclusion. Thus, plasma concentrations of creatine, cystathionine, kynurenic acid, and 3-hydroxykynurenine jointly reveal effects of vitamin B-6 restriction on the profiles of one-carbon and tryptophan metabolites and serve as biomarkers of functional effects of marginal vitamin B-6 deficiency.

Oral exposure to the anti-pyridoxine compound 1-amino d-proline further perturbs homocysteine metabolism through the transsulfuration pathway in moderately vitamin B6 deficient rats

“…These anti-pyridoxines, particularly hydrazines or its derivatives, can condense with the carbonyl group of PLP or PL to form corresponding hydrazones [18], resulting in distinctly reduced total endogenous B 6 vitamer pools. Subnormal plasma PLP concentrations have been shown to impair one carbon and methionine metabolism leading to the disturbance in nucleic acid synthesis because of the absence of methylene groups for 5,10-methylene-THF production [40]. As mentioned earlier, vitamin B 6 also plays a crucial role in Hcy metabolism, with deficiency leading to hyperhomocysteinemia, particularly in the fed state [27] and hypercystathioninemia [28].…”

Application of Metabolomics to Assess Effects of Controlled Dietary Interventions

“…Other investigations focusing on individual compounds or mixtures of compounds include studies such as vitamin B 6 restriction [38], calcium and vitamin D supplementation [21], vitamin E supplementation in relation to non-alcoholic steatohepatitis [27], effect of quercetin-containing supplements [37], supplementation with β-carotene in a cancer prevention study [43], Chia seed supplementation [30], and inclusion of fortified wheat flour (containing folic acid, vitamin B 1 , vitamin B 2 , ferric sodium edetate, and zinc oxide) in reducing the risk of neural tube defects [22]. All these studies report varying metabolic changes focusing mainly on their respective metabolic areas of interest, varying largely depending on the analytical approach and sample type used.…”

Vitamin B6 is essential for serine de novo biosynthesis

“…Most of the PLP-dependent reactions, such as transamination, decarboxylation, deamination, racemization and desulfhydration, are involved in amino acid metabolism (Ebadi 1981;Ueland et al 2015). PLP deficiency, either due to genetic or dietary causes, disrupts the metabolism of neurotransmitters (γ-aminobutyric acid (GABA), dopamine and serotonin), haeme, histamine, amino acids, carbohydrates and nucleotides (da Silva et al 2013;Ueland et al 2015).…”