164 Introduction to Human Nutrition
hydrolyzed to pyridoxal, which can cross cell mem-
branes, by extracellular alkaline phosphatase, then
trapped intracellularly by phosphorylation. Tissue
concentrations of pyridoxal phosphate are controlled
by the balance between phosphorylation and
dephosphorylation.
Some 80% of the body’s total vitamin B 6 is pyri-
doxal phosphate in muscle, mostly associated with
glycogen phosphorylase. This does not function as a
reserve of the vitamin and is not released from muscle
in times of defi ciency; it is released into the circula-
tion (as pyridoxal) in starvation, when glycogen
reserves are exhausted and there is less requirement
for phosphorylase activity. Under these conditions it
is available for redistribution to other tissues, and
especially the liver and kidneys, to meet the increased
need for transamination of amino acids to provide
substrates for gluconeogenesis.
Metabolic functions of vitamin B 6
Pyridoxal phosphate is a coenzyme in three main
areas of metabolism:
● in a wide variety of reactions of amino acids, espe-
cially transamination, in which it functions as the
intermediate carrier of the amino group, and decar-
boxylation to form amines
● as the cofactor of glycogen phosphorylase in muscle
and liver, where it is the phosphate group that is
catalytically important
● in the regulation of the action of steroid hormones.
Pyridoxal phosphate acts to remove the hormone–
receptor complex from DNA binding, and so ter-
minate the action of the hormones. In vitamin B 6
defi ciency there is increased sensitivity and respon-
siveness of target tissues to low concentrations of
steroid hormones, including estrogens, androgens,
cortisol, and vitamin D.
Vitamin B 6 defi ciency
Defi ciency of vitamin B 6 severe enough to lead to
clinical signs is extremely rare, and unequivocal defi -
ciency has only been reported in one outbreak, during
the 1950s, when babies were fed on a milk preparation
that had been severely overheated during manufac-
ture. Many of the affected infants suffered convul-
sions, which ceased rapidly following the administra-
tion of vitamin B 6.
The cause of the convulsions was severe impair-
ment of the activity of the pyridoxal phosphate-
dependent enzyme glutamate decarboxylase, which
catalyzes the synthesis of the inhibitory neurotrans-
mitter γ-aminobutyric acid (GABA), together with
accumulation of hydroxykynurenine as a result of
impaired activity of kynureninase, which is also pyri-
doxal phosphate dependent.
Moderate vitamin B 6 defi ciency results in a number
of abnormalities of amino acid metabolism, espe-
cially of tryptophan and methionine. In experimental
animals, a moderate degree of defi ciency leads to
increased sensitivity of target tissues to steroid
hormone action. This may be important in the devel-
opment of hormone-dependent cancer of the breast,
uterus, and prostate, and may therefore affect the
prognosis. Vitamin B 6 supplementation may be a
useful adjunct to other therapy in these common
cancers; certainly, there is evidence that poor vitamin
B 6 nutritional status is associated with a poor prog-
nosis in women with breast cancer.Vitamin B 6 requirements
Most studies of vitamin B 6 requirements have fol-
lowed the development of abnormalities of trypto-
phan and methionine metabolism during depletion
and normalization during repletion with graded
intakes of the vitamin. Although the tryptophan load
test is unreliable as an index of vitamin B 6 nutritional
status in fi eld studies, under the controlled conditions
of depletion/repletion studies it gives a useful indica-
tion of the state of vitamin B 6 nutrition.
Since the major role of vitamin B 6 is in amino acid
metabolism it is likely that protein intake will affect
vitamin B 6 requirements. Adults maintained on
vitamin B 6 -defi cient diets develop abnormalities of
tryptophan and methionine metabolism more quickly,
and their blood vitamin B 6 falls more rapidly, when
their protein intake is relatively high (80–160 g/day in
various studies) than on low protein intakes (30–50 g/
day). Similarly, during repletion of defi cient subjects,
tryptophan and methionine metabolism and blood
vitamin B 6 are normalized more rapidly at low than
at high levels of protein intake.
From such studies the average requirement for
vitamin B 6 is estimated to be 13 μg/g dietary protein,
and reference intakes are based on 15–16 μg/g dietary
protein.