Introduction to Human Nutrition

The Vitamins 181

they are cut, as a result of the release of ascorbate
oxidase from the plant tissue. Signifi cant losses of the
vitamin also occur in cooking, both through leaching
into the cooking water and also atmospheric oxida-
tion, which continues when foods are left to stand
before serving.

Absorption and metabolism of vitamin C

There is active transport of the vitamin at the intesti-
nal mucosal brush border membrane. Both ascorbate
and dehydroascorbate are absorbed across the buccal
mucosa by carrier-mediated passive processes.
Intestinal absorption of dehydroascorbate is carrier
mediated, followed by reduction to ascorbate before
transport across the basolateral membrane.
Some 80–95% of dietary ascorbate is absorbed at
usual intakes (up to about 100 mg/day). The frac-
tional absorption of larger amounts of the vitamin is
lower, and unabsorbed ascorbate from very high
doses is a substrate for intestinal bacterial meta-
bolism, causing gastrointestinal discomfort and
diarrhea.
About 70% of blood ascorbate is in plasma and
erythrocytes, which do not concentrate the vitamin
from plasma. The remainder is in white cells, which
have a marked ability to concentrate it.
Both ascorbate and dehydroascorbate circulate in
free solution, and also bound to albumin. About 5%
of plasma vitamin C is normally dehydroascorbate.
Both vitamers are transported into cells by glucose
transporters, and concentrations of glucose of the
order of those seen in diabetic hyperglycemia inhibit
tissue uptake of ascorbate.
There is no specifi c storage organ for ascorbate;
apart from leukocytes (which account for only 10%
of total blood ascorbate), the only tissues showing a
signifi cant concentration of the vitamin are the
adrenal and pituitary glands. Although the concentra-
tion of ascorbate in muscle is relatively low, skeletal
muscle contains much of the body’s pool of 900–
1500 mg (5–8.5 mmol).
Diketogulonate arising from dehydroascorbate can
undergo metabolism to xylose, thus providing a route
for entry into central carbohydrate metabolic path-
ways via the pentose phosphate pathway. However,
oxidation to carbon dioxide is only a minor fate of
ascorbate in humans. At usual intakes of the vitamin,
less than 1% of the radioactivity from [^14 C]-ascorbate
is recovered as carbon dioxide. Although more^14 CO 2

is recovered from subjects receiving high intakes of

the vitamin, this is the result of bacterial metabolism

of unabsorbed vitamin in the intestinal lumen.

The fate of the greater part of ascorbic acid is excre-

tion in the urine, either unchanged or as dehydro-

ascorbate and diketogulonate. Both ascorbate and

dehydroascorbate are fi ltered at the glomerulus then

reabsorbed. When glomerular fi ltration of ascorbate

and dehydroascorbate exceeds the capacity of the

transport systems, at a plasma concentration of

ascorbate between 70 and 85 μmol/l, the vitamin is

excreted in the urine in amounts proportional to

intake.

Metabolic functions of vitamin C

Ascorbic acid has specifi c roles in two groups of

enzymes: the copper-containing hydroxylases and the

2-oxoglutarate-linked iron-containing hydroxylases.

It also increases the activity of a number of other

enzymes in vitro, although this is a non-specifi c

reducing action rather than refl ecting any metabolic

function of the vitamin. In addition, it has a number

of non-enzymic effects due to its action as a reducing

agent and oxygen radical quencher.

Copper-containing hydroxylases

Dopamine β-hydroxylase is a copper-containing

enzyme involved in the synthesis of the catechol-

amines norepinephrine (noradrenaline) and epi-

nephrine (adrenaline) from tyrosine in the adrenal

medulla and central nervous system. The enzyme

contains Cu+, which is oxidized to Cu^2 + during the

hydroxylation of the substrate; reduction back to Cu+

specifi cally requires ascorbate, which is oxidized to

monodehydroascorbate.

Some peptide hormones have a carboxy-terminal

amide that is hydroxylated on the α-carbon by a

copper-containing enzyme, peptidylglycine hydroxy-

lase. The α-hydroxyglycine residue then decomposes

non-enzymically to yield the amidated peptide and

glyoxylate. The copper prosthetic group is oxidized in

the reaction, and, as in dopamine β-hydroxylase,

ascorbate is specifi cally required for reduction back

to Cu+.

Oxoglutarate-linked iron-containing

hydroxylases

Several iron-containing hydroxylases share a common

reaction mechanism, in which hydroxylation of the