The Vitamins 153Thiaminases that catalyze base exchange or
hydrolysis of thiamin are found in microorganisms
(including some that colonize the gut), a variety of
plants, and raw fi sh. The presence of thiaminase in
fermented fi sh is believed to be a signifi cant factor in
the etiology of thiamin defi ciency in parts of south-
east Asia.
Absorption and metabolism of thiamin
Thiamin is absorbed in the duodenum and proximal
jejunum, and then transferred to the portal circula-
tion by an active transport process that is inhibited by
alcohol. This may explain why alcoholics are espe-
cially susceptible to thiamin defi ciency.
Tissues take up both free thiamin and thiamin
monophosphate, then phosphorylate them further to
yield thiamin diphosphate (the active coenzyme) and,
in the nervous system, thiamin triphosphate.
Some free thiamin is excreted in the urine, increas-
ing with diuresis, and a signifi cant amount may also
be lost in sweat. Most urinary excretion is as thio-
chrome, the result of non-enzymic cyclization, as well
as a variety of products of side-chain oxidation and
ring cleavage.
There is little storage of thiamin in the body, and
biochemical signs of defi ciency can be observed
within a few days of initiating a thiamin-free diet.
Metabolic functions of thiamin
Thiamin has a central role in energy-yielding metabo-
lism, and especially the metabolism of carbohydrates.
Thiamin diphosphate (also known as thiamin pyro-
phosphate, see Figure 8.8) is the coenzyme for three
oxidative decarboxylation reactions: pyruvate dehy-
drogenase in carbohydrate metabolism, α-keto-
glutarate dehydrogenase in the citric acid cycle, and
the branched-chain keto-acid dehydrogenase involved
in the metabolism of leucine, isoleucine, and valine.
These three enzymes are multienzyme complexes that
catalyze oxidative decarboxylation of the substrate
linked to reduction of enzyme-bound lipoamide, and
eventually reduction of NAD+ to NADH.
Thiamin diphosphate is also the coenzyme for
transketolase, in the pentose phosphate pathway of
carbohydrate metabolism. This is the major pathway
of carbohydrate metabolism in some tissues, and an
important alternative to glycolysis in all tissues, being
the source of half of the NADPH required for fatty
acid synthesis.
Thiamin triphosphate has a role in nerve conduc-
tion, as the phosphate donor for phosphorylation of
a nerve membrane sodium transport protein.Thiamin defi ciency
Thiamin defi ciency can result in three distinct
syndromes:
● a chronic peripheral neuritis, beriberi, which may
or may not be associated with heart failure and
edema
● acute pernicious (fulminating) beriberi (shoshin
beriberi), in which heart failure and metabolic
abnormalities predominate, with little evidence of
peripheral neuritis
● Wernicke’s encephalopathy with Korsakoff ’s psy-
chosis, a thiamin-responsive condition associated
especially with alcohol and narcotic abuse.
In general, a relatively acute defi ciency is involved
in the central nervous system lesions of the Wernicke–
Korsakoff syndrome, and a high energy intake, as in
alcoholics, is also a predisposing factor. Dry beriberi
is associated with a more prolonged, and presumably
less severe, defi ciency, and a generally low food intake,
whereas higher carbohydrate intake and physical
activity predispose to wet beriberi.
The role of thiamin diphosphate in pyruvate dehy-
drogenase means that in defi ciency there is impaired
conversion of pyruvate to acetyl-CoA, and hence
impaired entry of pyruvate into the citric acid cycle.
Especially in subjects on a relatively high carbohy-
drate diet, this results in increased plasma concentra-
tions of lactate and pyruvate, which may lead to
life-threatening lactic acidosis. The increase in plasma
lactate and pyruvate after a test dose of glucose has
been used as a means of assessing thiamin nutritional
status.Dry beriberi
Chronic defi ciency of thiamin, especially associated
with a high carbohydrate diet, results in beriberi,
which is a symmetrical ascending peripheral neuritis.
Initially, the patient complains of weakness, stiffness
and cramps in the legs, and is unable to walk more
than a short distance. There may be numbness of the
dorsum of the feet and ankles, and vibration sense
may be diminished. As the disease progresses, the
ankle jerk refl ex is lost, and the muscular weakness
spreads upwards, involving fi rst the extensor muscles