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chapter 38
Vitamin Metabolism
T A B L E 3 8 -2
Metabolic Functions o f Ascorbate
A: As specific electron donor for enzymes and their
metabolic role.
Enzymes
Three collagen hydroxylases
Two enzymes in carnitine
biosynthesis
Dopamine ß-monooxygenase
Metabolic Role
Collagen biosynthesis
Carnitine is essential for
mitochondrial fatty
acid oxidation.
Necessary for the
synthesis of
norepinephrine
and epinephrine
4-hydroxyphenylpyruvate
Participates in tyrosine
dehydrogenase
metabolism
Peptidyl-glycine
Required for amidation
a-monooxygenase
of peptide hormones
B: As potential chemical reductant and/or
antioxidant in nonenzymatic reactions.
Reaction or Function
Consequence
Gastrointestinal iron absorption.
Increase
Oxidative DNA and/or protein damage.
Decrease
Low-density lipoprotein oxidation.
Decrease
Endothelial-dependent vasodilation.
Increase
Lipid peroxidation.
Decrease
Oxidants and nitrosamines in gastric juice.
Decrease
Extracellular oxidants from neutrophils.
Decrease
levels at values found in wild animals suggest that the
RDA is low by as much as an order of magnitude. This
discrepancy may arise from the use of a single criterion for
ascorbate repletion—prevention of scurvy—which may
not accurately reflect all the functions of ascorbate. For
example, it is not known whether enzymes that require
or are activated by ascorbate (see below) are fully active
in persons maintained on the RDA. The biological func-
tions requiring the greatest amount of ascorbate have to
be defined. The RDA for ascorbate intake of 60 mg/d is
currently under revision. Studies have suggested that an
ascorbate intake of
1 0 0 - 2 0 0
mg/d may be needed to pre-
vent adverse health effects due to vitamin C deficiency.
To maintain optimal health, the dietary guidelines encour-
age consumption of five servings of fruits and vegetables
per day.
Claims that consumption of massive doses of ascorbate
(
1 - 2
g/d or even higher quantities) can prevent or cure
common cold, cancer, or other ailments have no basis in
fact. Although ascorbate has low toxic effects, adverse
effects at high dose, such as hyperoxalemia (oxalate is a
catabolite of ascorbate) in patients undergoing dialysis, or
hemolysis in subjects with glucose-
6
-phosphate dehydro-
genase deficiency, have been reported.
Major dietary sources of vitamin C are fresh, frozen, and
canned citrus fruits. Other fruits, leafygreen vegetables,
and tomatoes are important contributors to ascorbate
intake. Human milk contains 30-55 mg/L, depending on
maternal intake of vitamin C. Exposure to copper, iron,
and oxygen can destroy vitamin C by oxidation. The vita-
min is heat-labile, so excessive cooking will degrade it.
D-Ascorbate
(isoascorbate
or
erythroascorbate),
fre-
quently used as a food preservative, has one-twentieth the
biological activity of L-ascorbate.
Absorption of vitamin C from the small intestine is a
carrier-mediated process that requires sodium at the lu-
minal surface. Transport is most rapid in the ileum and
resembles the sodium-dependent transport of sugars and
amino acids, but the carrier is distinct for each class of
compound. Some ascorbate may also enter by simple dif-
fusion. With dietary intake less than 100 mg/d, efficiency
of absorption is 80-90%. With intake equal to the RDA,
plasma ascorbate is 0.7-1.2 mg/dL, and the ascorbate pool
size is 1500 mg. Scurvy becomes evident when the pool is
less than 300 mg, at which point plasma ascorbate is 0.13-
0.24 mg/dL. Highest tissue concentrations of ascorbate are
in the adrenal gland (cortex > medulla).
Most signs of scurvy can be related to inadequate or ab-
normal collagen synthesis. Ascorbate enhances prolyl and
lysyl hydroxylase activities (Chapter 25). Collagen formed
in scorbutic patents is low in hydroxyproline and poorly
cross-linked, resulting in skin lesions, bone fractures, and
rupture of capillaries and other blood vessels. The abso-
lute amount of collagen made in scorbutic animals may
also decrease independently of the hydroxylation defect.
The anemia of scurvy may result from a defect in iron
absorption or folate metabolism.
Ascorbate
increases
the
activity
of
hydroxylases
needed for the conversion of p-hydroxyphenylpyruvate to
homogentisate (Chapter 17), synthesis of norepinephrine
from dopamine (Chapter 32), and two reactions in
carnitine synthesis (Chapter 18). It is not known whether
decreased activity of these enzymes contributes to the
clinical characteristics of scurvy. Although ascorbic acid
is needed for maximal activity of these enzymes
in vivo
and
in vitro
, most show some activity when other reducing
agents are used.
38.3 Vitamin-Responsive Inherited
Metabolic Disorders
The vitamin requirements indicated by the RDA
1
rep-
resent the amounts needed for normal health by most
individuals
in the population.
Following absorption,
'(See Table 38-1.)
