Vitamin B6: a molecule for human health?

Abstract

Vitamin B6 is an intriguing molecule that is involved in a wide range of metabolic, physiological and developmental processes. Based on its water solubility and high reactivity when phosphorylated, it is a suitable co-factor for many biochemical processes. Furthermore the vitamin is a potent antioxidant, rivaling carotenoids or tocopherols in its ability to quench reactive oxygen species. It is therefore not surprising that the vitamin is essential and unquestionably important for the cellular metabolism and well-being of all living organisms. The review briefly summarizes the biosynthetic pathways of vitamin B6 in pro- and eukaryotes and its diverse roles in enzymatic reactions. Finally, because in recent years the vitamin has often been considered beneficial for human health, the review will also sum up and critically reflect on current knowledge how human health can profit from vitamin B6.

Scheme 1

The three known pathways for PLP biosynthesis: one salvage pathway, and two de novo pathways, a DXP-dependent one and a DXP-independent one. Chemical structures: (5) PLP; (7) deoxyxylulose 5’-phosphate, (6) 4-(phosphohydroxy)-L-threonine; (11) glyceraldehyde 3’-phosphate; (12) dihydroxyacetone phosphate; (9) ribose 5’-phosphate; (10) ribulose 5’-phosphate, (13) glutamine, (3) PM, (4) PMP, (1) PN, (8) PNP, (2) PL.

Scheme 2

Enzymatic reaction that are targets for pharmaceutical approaches. Shown are only the PLP-dependent enzymes. (A) Synthesis of xanthurenic acid (14) from L-tryptophan (15), via the intermediates L-kynurenine (16) and 3-hydroxykynurenine (17). (B) Synthesis of putrescine (19) from L-ornithine (18), leading subsequently to the synthesis of spermidine (20) and other polyamines. (C) Synthesis of tetrahydrofolate (22) and serine (21) to glycine (23) and 5,10-methylenetetrahydrofolate (24). Note: in this and the next Schemes only the PLP-dependent enzymes are shown.

Scheme 3

Synthesis of L-cysteine (25) from L-homo-cysteine (26) via the intermediate L-cystathionine (27).

Scheme 4

Example for Advanced Glycation Endproduct Reaction of glucose with proteins or PM. On the right half: glucose (28) can react with lysine residues of proteins 29 to form an imine (Schiff base) 30 and an Amadori product 31. This latter can be further oxidized by metals to form the final AGE. pb, peptide bond. On the left half: PM (3) has been proven to be the most potent B₆ vitamer to compete for the formation of AGEs [73]. It is suggested to form first an imine 32 with the glucose, followed by a double cyclization to afford 33 rather than formation of an Amadori product [73].

Scheme 5

Synthesis of neurotransmitters in the brain. (A) Serotonin (34) is synthesized from L-tryptophan (15) via the intermediate 5-hydroxytryptophan (37). (B) Dopamine (35) is formed from L-tyrosine (39) via DOPA (38), and (C) GABA (36) is formed in a decarboxylation reaction from L-glutamate (40).