conspectus of researchon copper metabolism and requirements

1990 KARL E. MASON
that after oral administration of radio
active copper the isotope appears rapidly
in the blood, reaching maximum levels
within 1 to 3 hours, as further discussed
below. Concepts of the processes of absorp
tion of copper from dietary sources in man
are based in large part upon studies of
experimental animals.
Animal studies indicate that at least two
mechanisms are concerned in copper ab
sorption ( 132, 256 ). One of these, pre
sumably an energy-dependent one, in
volves the absorption of complexes of cop
per and amino acids. There is also evidence
that L-amino acids facilitate the absorption
of copper, and that absorption progres
sively decreases with increasing molecular
size of copper-amino acid complexes (408 ).
The other mechanism is an enzymatic one
involving the binding of copper to, and
successive release from, macromolecular
proteins.
Studies of experimental animals indicate
that mechanisms of copper storage and
transfer involve not only metallothionein as
first identified in the chick intestinal mu
cosa (733), but that there also may exist
a variety of metallothioneins, differing
slightly in amino-acid content and metalbinding
characteristics (518, 562). There
is real need for better determination of the
extent to which findings in experimental
animals have application to the problem of
copper absorption and metabolism in man.
This applies also to the many factors in
animals which are known to interfere with
copper absorption through various mecha
nisms (competition for binding sites by
zinc, perhaps to a much lesser extent by
cadmium; interactions between molyb
denum, sulphates and copper; the effects of
dietary phytates, and the influence of
ascorbic acid intake). In the case of the
latter, dietary deficiency results in in
creased liver and plasma copper (337),
whereas increased oral intake decreases
the absorption and retention of copper in
the chick (333), rabbit (370), pig (254)
and rat (199). Moreover, in the pig, high
intake of ascorbic acid can overcome the
effects of excess copper either by inter
fering with copper absorption or by in
creasing the absorption and utilization of
iron (254). Such evidence raises questions
as to whether due consideration has been
given to the secondary effects that may be
related to the somewhat astronomical hu
man intakes of ascorbic acid currently in
vogue. It is also important to note that the
type, configuration and degree of polymeri
zation of amino acids present in the in
testine can influence the absorption of cop
per (798). Moreover, little is known re
garding the chemical forms of copper in
foods, and the influence of different meth
ods of cooking upon its availability.
The great difficulty in determining that
portion of dietary copper which is ab
sorbed becomes apparent when one con
siders the many variable factors affecting
copper absorption such as: competition for
protein-binding sites in the intestinal lumen
and mucosa; inhibition of binding at these
sites; difficulties in measuring the amount
of copper secreted by the bile, by accessory
glands of the digestive tract and by the in
testinal mucosa; and possible reabsorption
by the intestinal mucosa of some of the
secreted copper. Excellent reviews of this
subject have been presented by Dowdy
(169), Evans (192), Hambidge and Wairavens
(301) and Van Campen (804).
Mechanisms
The general concept of the mechanism
involved in copper absorption is as follows:
from ingested foodstuff copper is released
either as ionic copper or as a copperamino
acid complex. In the intestinal
lumen there exists a high molecular weight
protein which binds copper and preferen
tially releases it to the plasma membranes
on the luminal side of the absorptive cells
of the mucosa. Within the absorptive cells
is metallothionein (or metallothionein-like
proteins) rich in sulfhydryl groups, which
binds copper through formation of mercaptide
bonds. Since this cuproprotein
serves as a storage depot and also releases
copper to the plasma cell membrane on the
serosal side, it is considered to provide one
of the protective and regulatory mecha
nisms in copper homeostasis. However, it
is not quite that simple, since its binding to
copper is constantly in competition with
other trace elements and can also be in
fluenced by other dietary components such
as the sulphate radical, phytates, fiber and
ascorbic acid.
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