chapter 38
Vitamin Metabolism
TA B LE 38-1 (
c o n tin u e d )
Therapeutic Vitamin
Daily Dose
Biochemical/Biological Defect
2 0
Megaloblastic anemia
(vitamin B f;
5-20 mg
Branched chain a-ketoacid
adult RDA -
/ 2 0 0 0
5-20 mg
1 0
ketoaciduria (maple syrup
urine disease)
Pyruvic acidemia
Lactic and pyruvic
acidemia; Leigh’s
encephalomy elopathy
Pyruvate decarboxylase
Pyruvate decarboxylase (low Km
*These disorders can be thought of as relative vitamin deficiency states. Not all patients will respond to vitamins owing to the existence of pheno-
copies. Data from L. E. Rosenberg: Vitamin-responsive inherited metabolic disorders. In
A d v a n c e s in H u m a n G e n e tic s ,
, H. Harris and
K. Hirschhom, Eds. (Plenum Press, 1976); and S. H. Mudd: Vitamin-responsive genetic abnormalities, In
A d v a n c e s in N u tr itio n a l R e se a rc h ,
Vol. 4
(Plenum Press, 1982).
+A11 disorders have an autosomal recessive pattern of inheritance except as follows:
*X-linked dominant inheritance;
§ Pattern of inheritance unknown;
^Autosomal, probably recessive, inheritance;
‘HX-linked recessive inheritance.
4. The biochemical function of the vitamin should be
related directly to the observed deficiency symptoms,
although this is not always possible to demonstrate.
The classic example is
(scorbutus), which used
to be common among sailors who ate no fresh fruit or
vegetables during long sea voyages. Scurvy could be
prevented by consumption of fresh citrus fruits, now
known to be high in vitamin C (ascorbic acid). The
deficiency arose because vitamin C was destroyed by
the methods used to preserve food while at sea. Other
examples of a single vitamin deficiency in human
populations are rare, however, except where the
dietary supply is adequate but utilization of the
vitamin is impaired. Frequently, if one vitamin is
lacking, others are as well, and the intake of protein,
trace elements, and other nutrients is probably
insufficient. This is particularly true of B vitamins.
In addition to nutritional inadequacy, vitamin deficiency
may result from malabsorption, effects of pharmacolo-
gical agents, and abnormalities of vitamin metabolism or
utilization. Thus, in biliary obstruction or pancreatic dis-
ease, the fat-soluble vitamins are poorly absorbed despite
adequate dietary intake because of steatorrhea. Absorp-
tion, transport, activation, and utilization of vitamins re-
quire the participation of enzymes or other proteins whose
synthesis is under genetic control. Dysfunction or absence
of one of these proteins can produce a disease that is
clinically indistinguishable from one caused by dietary
deficiency. In vitamin-dependent or vitamin-responsive
disorders, use of pharmacological doses of the vitamin can
sufficiently overcome the blockage for normal function to
occur (Table 38-1; discussed at the end of the chapter).
Vitamin deficiency can result from treatment with cer-
tain drugs. Thus, destruction of intestinal microorgan-
isms by antibiotic therapy can produce symptoms of
vitamin K deficiency. Isoniazid, used to treat tuberculo-
sis, is a competitive inhibitor of pyridoxal kinase, which
is needed to produce pyridoxal phosphate. Isoniazid can
produce symptoms of pyridoxine deficiency. To prevent
this, pyridoxine is often incorporated into isoniazid tablets.
Methotrexate and related folate antagonists act by compet-
itively inhibiting dihydrofolate reductase (Chapter 27).
Two standards have been established to plan diets that
contain adequate supplies of the vitamins and to aid in
diagnosing vitamin deficiency diseases.
1. The
minimum daily requirement
(MDR) is the
smallest amount of a substance needed by a person to
prevent a deficiency syndrome. It is considered to
represent the body’s basic physiological requirement
of the material. MDR values, which are established
by the U.S. Food and Drug Administration (FDA), are
not available for all vitamins.
2. The
recommended daily allowance
(RDA) is the
amount of a compound needed daily to maintain good
nutrition in most healthy people. RDA values are
intended to serve as nutritional goals, not as dietary
requirements. They are defined by the Food and
Nutrition Board of the National Academy of Sciences
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