American Academy of Pediatrics Committee on Nutrition Vitamin B6 Requirements in Man

VITAMIN B6 REQUIREMENTS IN MAN I rc 1934 Gyorgy1 reported experimental studies on the relation of a dietary factor to rat dermatitis and established this nutrient as a new member of the B-Cornplex, calling it vitamin B6. The vitamin subsequently isolated26 and synthesized was found to be 2 methyl-3 hydroxy-4, 5 hydroxy methyl pyridine and called pyridoxine.7 By means of an elegant series of experiments, Snell discovered that vitamin B6 exists in three interchangeable forms, pyridoxine, pyridoxal, pyridoxamine, all of which are phosphorylated in vivo, as shown in Figure 1.8,9 The vitamin is eventually metabolized to pyridoxic acid and excreted in the urine.10 Pyridoxal phosphate, biochemically the major active form of this group, functions as a coenzyme in virtually all of the reactions involving amino acids, such as transamination, deamination, decarboxylation, racemization, amine ixodation, as well as elimination and additive reactions.11’12 Pyridoxal phosphate is also a significant component of muscle phosphorylase a and b, the enzyme that initiates the first step in glycogenolysis, leading to formation of glucose 1 phosphate.l3 Furthermore, pyridoxal phosphate has been implicated in fat metabolism through its relation to phospholipids and cholesterol esters, fatty acid transport, and control of adipose tissue composition.14 Since vitamin B6 is involved in such a large number of crucial biochemical reactions, a variety of metabolic disorders may result from a deficiency of this vitamin.15 The integrity of each biochemical reaction seems to depend on the individual rank order of affinity of the apoenzyme for pyridoxal phosphate and the avidity of binding with pyridoxal phosphate.16 In the disease states referred to as “vitamm B6 dependency,” it has been proposed that an inborn or acquired structural abnormality has changed the binding capacity of the specific B-dependent apoenzymes to the cofactor and that only larger amounts of pyridoxal phosphate can overcome adverse binding kinetics’7’18 Bonner19 has demonstrated specific mutations affecting the B6 binding site of an apoenzyme. Frimpter2#{176} recently presented evidence which strongly supports the concept of an altered binding site as the mechanism of B6 dependency. It has also been confirmed that both metabolism and availability of the vitamin are normal in at least one form of B6 dependency.21 In an mdividual with B6 dependency, in contrast to the excessive needs by the abnormal enzymes for pyridoxine, the other enzymatic reactions requiring B6 proceed normally in the presence of the usual concentrations of the vitamin.