BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 8. VITAMINS

8.3. Water-soluble vitamins

8.3.6. Vitamin B₆ — Pyridoxine

Structure and physicochemical properties. Vitamin B₆ is a collective term for three 3-hydroxypyridine derivatives: pyridoxal, pyridoxine, and pyridoxamine, which differ in the Chemical Nature of the substituent group at the fourth position of the pyridine ring (Fig. 8.18, A). All forms of the vitamin are readily soluble in Water and stable against acids, alkalis, and heat. The coenzyme Functions are performed by phosphorylated derivatives of pyridoxal and pyridoxamine, which are interconvertible. Phosphorylation is mediated by a specific pyridoxase (pyridoxal kinase), which exhibits its highest activity in the Brain (Fig. 8.18, B).

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Fig. 8.18. Forms of vitamin B₆ (A) and The formation of Pyridoxal phosphate (B)

Biochemical functions. Pyridoxal phosphate and pyridoxamine phosphate are essential Coenzymes in Amino acid METABOLISM. They mediate AMINO ACID Transamination and decarboxylation reactions. Pyridoxal phosphate forms complexes with enzyme Proteins, ensuring reaction Specificity. In this process, the carbonyl group of the coenzyme binds to the ε-amino group of a Lysine residue in the apoenzyme. The incoming amino acid attaches via its amino group to the aldehyde group of pyridoxal phosphate to form a Schiff base, displacing the lysine amino group (Fig. 8.19). This is accompanied by the labilization of one of the three bonds adjacent to the α-carbon atom of The amino acid molecule.

Fig. 8.19. Attachment of an amino acid to the aldehyde group of pyridoxal phosphate

Consequently, Amino Acids can participate in Three types of reactions: transamination, decarboxylation, and aldol Cleavage.

Transamination reactions involve α-ketoglutaric acid, which interacts with Almost all amino acids. The most thoroughly studied Enzymes in this group are aspartate aminotransferase and Alanine aminotransferase.

Unlike transamination, decarboxylation reactions are irreversible. They are generally utilized for the synthesis of various compounds. Aromatic amino acid decarboxylase, found in high concentrations in the Adrenal Glands and the Central Nervous system, takes part in the synthesis of biologically active amines, such as dopamine.

Decarboxylation coupled with Condensation reactions is involved in the Synthesis of the amino alcohol sphingosine and δ-aminolevulinic acid, which is the initiating precursor in heme synthesis. The decarboxylation of a Cysteine derivative yields taurine, which is required for the synthesis of conjugated Bile acids.

Pyridoxal phosphate is also a structural component of Glycogen phosphorylase, an enzyme involved in glycogen breakdown.

Occurrence in nature. Vitamin B₆ deficiency is rare; it has been most extensively studied in rats, in which it manifests as a specific dermatitis known as acrodynia. This condition affects the paws, tail, Nose, and ears, causing Skin peeling, Hair loss, limb ulcerations, and toe gangrene. Convulsions have also been reported in infants when vitamin levels drop to 50% of the normal value. The daily requirement is 2–3 mg, with Liver, fish, meat, buckwheat, potatoes, peas, and beans serving as the primary dietary sources.

In medical practice, isoniazid is used as an antituberculosis drug. Isoniazid acts as a pyridoxal antagonist and primarily inhibits pyridoxase activity. Since the kinase content in mycobacteria is very low, blocking this enzyme leads to the suppression of bacterial growth.