section 38.2
Water-Soluble Vitamins
Absorption, Transport, and Metabolism
Thiamine is absorbed by a pathway that is saturable
at concentrations of 0.5-1.0 /xmoI/L. Oral doses in ex-
cess of
1 0
mg do not significantly increase blood or urine
concentrations of vitamin Bj. In the human, absorption
occurs predominantly in the jejunum and ileum. Some
ferns, shellfish, fish, and species of bacteria contain thiami-
nase, which cleaves the pyrimidine ring from the thiazole
ring. This enzyme causes thiamine deficiency in cattle. In
plasma, thiamine is transported bound to albumin and, to
a small extent, other proteins. TPP is synthesized in the
liver by thiamine pyrophosphokinase.
In humans, TPP is a coenzyme for transketolation,
an important reaction in the pentose-phosphate pathway,
and for the oxidative decarboxylations catalyzed by pyru-
vate dehydrogenase, branched-chain a-ketoacid decar-
boxylase, and o'-kctoglutaratc dehydrogenase complexes.
In lower organisms, TPP is also a cofactor for nonoxida-
tive decarboxylations such as the conversion of pyruvate
to acetaldehyde that occurs in yeast.
TPP and TTP occur in the central nervous system
and play an important part in brain metabolism. En-
try of thiamine into cerebrospinal fluid may occur via
a saturable transport mechanism, perhaps located in the
choroid plexus.
Hypo- and Hypervitaminosis
Major diseases caused by thiamine deficiency are the
Wernicke-Korsakoff syndrome,
with chronic alcoholism, and
the classic thiamine
deficiency syndrome. Both are related to diets high in car-
bohydrate and low in vitamins. The Wernicke-Korsakoff
Wernicke’s encephalopathy
Korsakoff’s psychosis.
The encephalopathy presents with
ataxia, confusion, and paralysis of the ocular mus-
cles, which are relieved by administration of thiamine.
Korsakoff’s psychosis is characterized by amnesia and
is only slightly responsive to thiamine. These disorders
reflect different stages of the same pathological process.
Some areas within the brain appear to be more suscepti-
ble than others to the effects of thiamine depletion. The
nature of the biochemical lesion is unknown. Thiamine
deficiency in chronic alcoholics probably has multiple
causes, including poor diet, an inhibitory effect of alco-
hol and of any accompanying folate deficiency on in-
testinal transport of thiamine, and reduced metabolism
and storage of thiamine by the liver due to alcoholic
Beriberi occurs whenever thiamine intake is less than
0.4 mg/d for an extended period of time. It occurs where
polished rice is a dietary staple, and, in Western society, in
poor and elderly populations and alcoholics. Beriberi has
wet, dry, and cardiac types, and an individual may have
more than one type. “Wet” refers to pleural and peritoneal
effusions and edema; “dry” refers to polyneuropathy with-
out effusions. Cardiomyopathy is the principal feature of
the cardiac type. An infantile form occurs in breast-fed
infants, usually 2-5 months of age, nursing from thiamine-
deficient mothers. The symptoms of beriberi remit com-
pletely upon thiamine supplementation. A subclinical de-
ficiency of thiamine occurs in hospital patients and the
elderly. Deficiency of thiamine and other vitamins may
contribute to a generally reduced state of health in these
Thiamine deficiency can be assessed by measuring
blood levels. Increased blood levels of pyruvate and lactate
suggest thiamine deficiency. Measurement of erythrocyte
transketolase activity, which requires TPP as a coenzyme,
confirms the deficiency.
Four inherited disorders responsive to treatment with
pharmacological doses of thiamine are summarized in
Table 38-1. However, at least for megaloblastic anemia
and maple syrup urine disease, more nonresponsive than
responsive cases are known. Since thiamine is promptly
excreted in the urine, excessive intake is not associated
with toxicity.
Riboflavin (Vitamin B
This vitamin is the precursor of flavin mononucleotide
(FMN) and flavin adenine dinucleotide (FAD), cofactors
for several oxidoreductases that occur in all plants, ani-
mals, and bacteria (Figure 38-13).
The FAD-requiring enzymes in mammalian systems
include the D- and L-amino acid oxidases, mono- and
diamine oxidases, glucose oxidase, succinate dehydroge-
nase, a-glycerophosphate dehydrogenase, and glutathione
reductase. FMN is a cofactor for renal L-amino acid
oxidase, NADH reductase, and a-hydroxy acid oxidase.
In succinate dehydrogenase, FAD is linked to a histidyl
residue; in liver mitochondrial monoamine oxidase, to a
cysteinyl residue. In other cases, the attachment is nonco-
valent but the dissociation constant is very low.
Use of oral contraceptives may increase the dietary re-
quirement for riboflavin. Riboflavin status can be evalu-
ated from the activity of erythrocyte glutathione reduc-
tase, an FAD-requiring enzyme, before and after addition
of exogenous FAD. A low initial activity or a marked
stimulation by FAD (or both) is indicative of ariboflavi-
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