Vitamin B₆ and Its Role in Cell Metabolism and Physiology

Abstract

Vitamin B₆ is one of the most central molecules in cells of living organisms. It is a critical co-factor for a diverse range of biochemical reactions that regulate basic cellular metabolism, which impact overall physiology. In the last several years, major progress has been accomplished on various aspects of vitamin B₆ biology. Consequently, this review goes beyond the classical role of vitamin B₆ as a cofactor to highlight new structural and regulatory information that further defines how the vitamin is synthesized and controlled in the cell. We also discuss broader applications of the vitamin related to human health, pathogen resistance, and abiotic stress tolerance. Overall, the information assembled shall provide helpful insight on top of what is currently known about the vitamin, along with addressing currently open questions in the field to highlight possible approaches vitamin B₆ research may take in the future.

Keywords: PLP; cell; health; metabolism; pathogen; physiology; pyridoxine; stress; vitamin B6.

Figure 1

Chemical structures of the six common B₆ vitamers. (a,b): Pyridoxal (a) and its phosphorylated form pyridoxal 5′-phosphate (b), (c,d): pyridoxamine (c) and pyridoxamine 5′-phosphate (d), (e,f): pyridoxine (e) and pyridoxine 5′-phosphate (f).

Figure 2

The two known de novo pathways leading to the biosynthesis of PLP. The two de novo pathways, DXP-dependent and -independent, use pyridoxine 5′-phosphate synthase (PDXJ) and 4-hydroxythreonine-4-phosphate dehydrogenase (A) and PDX1 and 2 enzyme, respectively, to synthesize PLP. DXP, Deoxyxylose 5′-phosphate; DAP, Dihydroxyacetone phosphate; DXP, 1-Deoxyxylulose-5-phosphate; GAP, Glyceraldehyde-3-phosphate; GLN, L-Glutamine; GLU, L-Glutamate; PHT, 4-Phosphohydroxy-L-threonine; PLP, Pyridoxal-5-phosphate; PNP, Pyridoxine-5-phosphate; RIP, Ribose-5-phosphate; RUP, Ribulose-5-phosphate.

Figure 3

The VitB₆ salvage pathway. The salvage pathway is used to derivatize and phosphorylate B₆ vitamers, leading to PLP synthesis via oxidase (PDXH), kinase (K), and pyridoxal reductase (PRL) enzymes.

Figure 4

Schematic of known and potential vitB₆ transporters. In the yeasts S. cerevisiae and S. pombe, import of vitB₆ across the plasma membrane is facilitated by Tpn1p and Bsu1, respectively. In plants, members of the amino acid permease family (here PUP1) perform this function. In humans, there is no confirmed transporter for vitB₆, but this may be accomplished by BsuI orthologs. In the bacterial phylum firmicutes, a modular transporter called PdxT transports B₆ vitamers into the cell. Mtm1p is a carrier from S. cerevisiae that imports PLP into the mitochondria. De novo and salvage pathways are labeled according to their presumed subcellular localization and presence in the respective organism.

Figure 5

Schematic drawing of neurotransmitter biosynthesis that involve PLP-dependent enzymes. B6, vitB₆; L-DOPA, L-3′-4′-dihydroxyphenylalanine; 5′-HTP, 5′-hydroxytryptophan; 5′-HT, 5′-hydroxytryptamine.

Figure 6

Schematic drawing of the 1-carbon methylation cycle. The methionine and the folate cycle, as well as the transulfuration pathway, are three interrelated routes involved in one-carbon metabolism, which is required for the synthesis of amino acids, neurotransmitters, and methylation of DNA and proteins. B6, vitB₆; B12, vitB₁₂; BH4, tetrahydrobiopterin; CBS, cystathionine-β-synthase; MAT, methionine adenosyltransferase; MS, methionine synthase; MT, methyltransferase; MTHFR, methylenetetrahydrofolate reductase; SAH, S-adenosylhomocysteine; SAHH, S-adenosylhomocysteine hydrolase; SAM, S-adenosylmethionine; SHMT, serine hydroxymethyltransferase; THF, tetrahydrofolate.