Heterocycles in Nature 161Pyridoxine (vitamin B 6 ) and pyridoxal phosphate (PLP)
Vitamin B 6 is transformed into pyridoxal phosphate (PLP), which, as a pyridine, is basic at the ring nitrogen,
and in the active form, is N-protonated. Enzymes containing PLP have various functions, all connected with
-amino acids. Amongst other activities, PLP-containing enzymes can: (i) effect transfer of an amino group from
an-amino acid to an -keto-acid, (ii) bring about decarboxylation of an -amino acid, or (iii) bring about
de-amination of an -amino acid. In each case, the chemistry of the process depends critically on the intrinsic
chemical reactivity of the pyridine. Consider decarboxylation: condensation of the pyridine-4-aldehyde with the
amino group of an -amino acid generates an imine, which is stabilised by hydrogen bonding with the adjacent
phenolic hydroxyl group. The decarboxylation is promoted by the flow of electrons from the breaking C-C bond
through to the positively charged pyridine nitrogen, generating an extensively conjugated enamine–imine sys-
tem, which regains the aromaticity of the pyridine ring by C-protonation. Finally, a standard hydrolysis of the
new imine link produces the amine corresponding to the original -amino acid, together with the regenerated
co-enzyme.
Thiamin (vitamin B 1 ) and thiamine pyrophosphate
Thiamin pyrophosphate acts as a co-enzyme in several biochemical processes and, in each case, its mode of
action depends on the intermediacy of a 2-deprotonated species – an ylide (see pages 113–114 for a discussion).
For example, in the later stages of alcoholic fermentation, which converts glucose into ethanol and carbon diox-
ide, the enzyme pyruvate decarboxylase catalyses the conversion of pyruvate into ethanal (acetaldehyde) and
carbon dioxide, the former then being converted into ethanol by the enzyme alcohol dehydrogenase. Thiamin
pyrophosphate, in the form of its ylide, adds to the ketonic carbonyl group of pyruvate; this is followed by loss
of carbon dioxide then the release of ethanal by expulsion of the original ylide as a leaving group, to continue
the cycle. In the laboratory, thiazolium salts will act as nucleophilic catalysts by utilising this ability to form an
ylide by C-2-deprotonation.