Vitamin Metabolism
show neurological signs despite normal serum levels of
vitamin E, which may arise from the associated increase
in levels of serum lipids, which contain vitamin E. In
patients with cystic fibrosis, steatorrhea and fat malab-
sorption with subnormal plasma and tissue concentrations
of vitamin E are common, but neuromuscular disorders
such as those in chronic cholestasis do not occur.
Vitamin E deficiency occurs due to genetic defects in the
formation of hepatic a-tocopherol transfer protein. This
transport protein plays a central role in the liver and one of
its functions is to facilitate incorporation of a-tocopherol
into nascent very low density lipoproteins (VLDLs). Since
there are no specific transport proteins for vitamin E in
plasma, the delivery of vitamin E to the tissues is pri-
marily mediated by VLDL-LDL transport mechanisms
(Chapter 20). Thus, deficiency of hepatic a-tocopherol
transport protein causes low plasma levels of vitamin E
with impairment of delivery to the tissues. Patients with the
transport protein deficiency exhibit peripheral neuropathy
and ataxia. Early and vigorous vitamin E supplementation
in patients with neurological symptoms and with low plas-
mal levels of vitamin E has yielded therapeutic benefits.
A pharmacological role for vitamin E may exist in
claudication arising from peripheral vascular disease.
Studies with small numbers of patients having cystic fibro-
sis, glucose-
-phosphate dehydrogenase deficiency, and
sickle cell anemia conditions associated with decreased
erythrocyte half-lives showed that many had chemi-
cal evidence of vitamin E deficiency. Administration of
vitamin E supplements (400-800 IU/d) significantly
increased red cell survival time. Claims that doses of
vitamin E 10-20 times the RDA are beneficial for treat-
ment of skin disorders, fibrocystic breast disease, sexual
dysfunction, cancer, baldness, and other disorders have
not been substantiated.
Self-medication with high doses of vitamin E appears
to be relatively nontoxic. However, in patients receiving
warfarin (Chapter 36), vitamin E in excess of400 IU/d may
further depress coagulability and produce coagulopathy.
38.2 Water-Soluble Vitamins
The B group vitamins and vitamin C serve as coenzymes or
coenzyme precursors. The B complex includes thiamine,
riboflavin, pyridoxine, niacin, pantothenic acid, biotin, fo-
late, and cobalamin. Inositol, choline, and paraaminoben-
zoic acid, usually classified as vitamin-like substances
in humans, are sometimes included with the B-complex
vitamins. They will be discussed briefly at the end of
the chapter. The B vitamins occur in protein-rich foods
and in dark green, leafy vegetables. A deficiency of one
B vitamin is usually accompanied by deficiencies of oth-
ers in the group and of protein. Vitamin C is the anti-
scorbutic factor of citrus fruit and other fresh fruits and
vegetables. Symptoms of deficiency of the water-soluble
vitamins are similar and include disorders of the nervous
system and of rapidly dividing tissues, such as the gastroin-
testinal epithelium, mucous membranes, skin, and cells of
the hematopoietic system.
Thiamine (Vitamin Bj)
Nutrition and Chemistry
This vitamin, also called aneurin, is the antiberiberi fac-
tor. The active coenzyme form is thiamine pyrophosphate
(TPP), or cocarboxylase. Thiamine triphosphate (TTP)
may be an active form in the central nervous system. Of the
thiamine in the body, 10% occurs as TTP, 80% as TPP, and
10% as TMP (thiamine monophosphate) (Figure 38-12).
The principal dietary sources include fish, lean meat
(especially pork), milk, poultry, dried yeast, and whole-
grain cereals. Bread, cereals, and flour-based products are
frequently enriched with this vitamin. Thiamine is present
in the outer layers of rice grains, from which it was first
identified. Deficiency is common in Asian countries where
polished rice is the principal dietary staple. The RDA de-
pends on energy intake.
r *
i f ^
-CH jCHjO -
C om pound
= B
Thiam ine
— H
— p — <
— P — O — P — 0 “
o r
— P — O — P — o —
l _
F IG U R E 3 8 -1 2
Structures of thiamine (vitamin Bi) and its phosphorylated metabolites.
They consist of a six-membered pyrimidine ring and a five-membered
thiazole ring, linked through a methylene group.
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