Discovery of pyridoxal reductase activity as part of human vitamin B6 metabolism

Ramos, Rúben J.; Albersen, Monique; Vringer, Esmee; Bosma, Marjolein; Zwakenberg, Susan; Zwartkruis, Fried; Jans, Judith; Verhoeven‐Duif, Nanda M.

doi:10.1016/j.bbagen.2019.03.019

Cited by 26 publications

(18 citation statements)

References 23 publications

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“…Indeed, a recent study discovered a pyridoxal reductase as part of the human B6 metabolism. This enzyme is responsible for the reduction of PL to PN, and can explain the small amount of PN in our experiment [46] (Fig. 1).…”

Section: Discussionmentioning

confidence: 62%

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Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine

et al. 2021

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Background and aims: Vitamin B6 is involved in a large spectrum of physiological processes and comprises of the vitamers pyridoxamine (PM), pyridoxal (PL), pyridoxine (PN), and their phosphorylated derivatives including the biological active pyridoxal 5 0 -phosphate (PLP). While PN toxicity is known to complicate several treatments, PM has shown promise in relation to the treatment of metabolic and agerelated diseases by blocking oxidative degradation and scavenging toxic dicarbonyl compounds and reactive oxygen species. We aimed to assess the metabolization of oral PM supplements in a single and three daily dose. Materials and methods: We optimized and validated a method for the quantification of the B6 vitamers in plasma and urine using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five healthy volunteers were recruited to study PM metabolization after a single oral dose of 200 mg PM or a three daily dose of 67 mg PM. A third protocol was implemented as control for dietary intake. Venous blood samples, 24 h urine and fasted second void urine samples were collected. Results: After a single oral dose of 200 mg PM, plasma PM increased in the first 3 h to a maximum of 2324 ± 266 nmol/L. While plasma PM levels returned to baseline after~10 h of PM intake, PLP increased to a maximum of 2787 ± 329 nmol/L and reached a plateau. We found a small increase of PN to a maximum of 13.5 ± 2.1 nmol/L; it was nearly undetectable after~12 h. With a three daily dose of 67 mg PM we observed an increase and decline of plasma PM, PL, and PN concentrations after each PM intake. PLP showed a similar increase as in the single dose protocol and accumulated over time. Conclusion:In this study we showed high plasma levels of PM after oral PM supplementation. We found steadily increasing levels of the biologically active PLP, with minimal formation of PN. The B6 vitamer PM is an interesting supplement as an inhibitor of harmful processes in metabolic diseases and for the treatment of vitamin B6 deficiency. Clinical trial registry: The study was approved by the Medical Ethics Committee of Maastricht University (NL) and was registered at ClinicalTrials.gov as NCT02954588.

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Section: Discussionmentioning

confidence: 62%

“…Pyridox (am)ine phosphate oxidase (PNPO) converts PMP and PNP to PLP. Recently, it has been shown that PL can also be converted to PN in humans by a pyridoxal reductase [46] (dotted grey arrow).…”

Section: Discussionmentioning

confidence: 99%

Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine

et al. 2021

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“…In addition, they have a salvage pathway, which generates PLP from any of the other five B 6 vitamers [ 73 ]. Humans lack a de novo biosynthesis pathway, but they have the required salvage pathway enzymes [ 74 , 75 ]. The vitamin is therefore essential for the human diet, and any of the six B 6 vitamers can be used as a PLP resource.…”

Section: Vitamin-based Antioxidantsmentioning

confidence: 99%

Antioxidants in Potatoes: A Functional View on One of the Major Food Crops Worldwide

2021

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With a growing world population, accelerating climate changes, and limited arable land, it is critical to focus on plant-based resources for sustainable food production. In addition, plants are a cornucopia for secondary metabolites, of which many have robust antioxidative capacities and are beneficial for human health. Potato is one of the major food crops worldwide, and is recognized by the United Nations as an excellent food source for an increasing world population. Potato tubers are rich in a plethora of antioxidants with an array of health-promoting effects. This review article provides a detailed overview about the biosynthesis, chemical and health-promoting properties of the most abundant antioxidants in potato tubers, including several vitamins, carotenoids and phenylpropanoids. The dietary contribution of diverse commercial and primitive cultivars are detailed and document that potato contributes much more than just complex carbohydrates to the diet. Finally, the review provides insights into the current and future potential of potato-based systems as tools and resources for healthy and sustainable food production.

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“…Pyridoxal 5'-phosphate (PLP) is an essential co-factor involved in vital metabolic pathways, including neurotransmitter production and amino acid biosynthesis (1,2). Like all other mammals, humans cannot synthesize PLP de novo and therefore require the dietary uptake of the inactive B 6 vitamers pyridoxine (PN), pyridoxal (PL), and pyridoxamine (PM) which are subsequently converted into catalytically active PLP (3). Bioregulation of PLP involves three enzymes namely, pyridoxal kinase (PDXK), pyridoxamine 5'-phosphate oxidase (PNPO) and pyridoxal phosphatase (PDXP).…”

Section: Introductionmentioning

confidence: 99%

“…PDXK catalyzes the ATP-dependent phosphorylation of the B 6 vitamers PN, PL and PM to their phosphorylated counterparts PNP (pyridoxine 5'phosphate), PLP and PMP (pyridoxamine 5'-phosphate) (4). PNPO catalyzes the conversion from PNP and PMP into PLP, which is the metabolically active form of vitamin B6 (3,5).…”

Section: Introductionmentioning

confidence: 99%

Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism

Keller

Mendoza-Ferreira

Maroofian

et al. 2020

Neuromuscular Disorders

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Discovery of pyridoxal reductase activity as part of human vitamin B6 metabolism

Cited by 26 publications

References 23 publications

Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine

Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine

Antioxidants in Potatoes: A Functional View on One of the Major Food Crops Worldwide

Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism

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