Vitamin B6 in the form of PLP and, to a lesser degree, pyridoxamine phosphate play an essential role in the interaction of amino acid, carbohydrate and fatty acid metabolism in the energy-producing TCA cycle. Over 60 enzymes are already known to depend on vitamin B6 coenzymes. Pyridoxal phosphate functions in practically all reactions involved in amino acid metabolism, including transamination, decarboxylation, deamination, and desulfhydration, as well as the cleavage or synthesis of amino acids.
Vitamin B6 participates in functions that include (Bräunlich, 1974; Marks, 1975; Driskell, 1984):
- Deaminases–for serine, theonine and cystathionine.
- Desulfydrases and transulfurases–interconversion.
- Synthesis of niacin from tryptophan–hydroxykynurenine is not converted to hydroxyanthranilic acid, but rather to xanthurenic acid due to lack of the B6-dependent enzyme, kynureninase.
- Formation of alpha-aminolevulinic acid from succinyl CoA and glycine, the first step in porphyrin synthesis.
- Conversion of linoleic to arachidonic acid in the metabolism of essential fatty acids (this function is controversial).
- Glycogen phosphorylase catalyzes glycogen breakdown to glucose-1-phosphate. Pyridoxal phosphate does not appear to be a coenzyme for the enzyme but rather to affect the enzyme conformation.
- Synthesis of epinephrine and norepinephrine from either phenylalanine or tyrosin–both norepinephrine and epinephrine are involved in carbohydrate metabolism as well as in other body reactions.
- Racemases–PLP-dependent racemases enable certain microorganisms to utilize D-amino acids. Racemases have not yet been detected in mammalian tissues.
- Transmethylation involving methionine.
- Incorporation of iron in hemoglobin synthesis.
- Formation of antibodies–B6 deficiency results in inhibition of the synthesis of globulins that carry antibodies.
Neurological disorders, including states of agitation and convulsions, result from reduction of B6 enzymes in the brain, including glutamate decarboxylase and gamma-aminobutyric acid transaminase. Maternal restriction of B6 in rats adversely affected synaptogenesis, neurogenesis and neuron longevity, and differentiation of the progeny (Groziak and Kirksey, 1997; 1990). Recent work in animal models suggests that vitamin B6 deficiency during gestation and lactation alters the function of N-methyl-D-aspartate receptors, a subtype of receptors of the glutamatergic neurotransmitter system thought to play an important role in learning and memory (Guilarte, 1993).
Animal and human studies suggest that a vitamin B6 deficiency affects both humoral and cell-mediated immune responses. In humans, vitamin B6 depletion significantly decreased percentage and total number of lymphocytes, mitogenic responses of peripheral blood lymphocytes to T- and B-cell mitogens and interleukin 2 production (Meydani et al., 1991). Additional human studies indicate that vitamin B6 status may influence tumor growth and disease processes. Deficiency of the vitamin has been associated with immunological changes observed in the elderly, persons infected with human immunodeficiency virus (HIV) and those with uremia or rheumatoid arthritis (Rall and Meydani, 1993).
