conspectus of researchon copper metabolism and requirements

1982 KARL E. MASON
year Daniels and Wright (142) reported
the first balance study on young children
(4-6 years old) indicating an average in
take of 1.48 mg/day and a requirement
not less than 0.10 mg/kg/day. These esti
mates are in remarkably good agreement
with those recorded in the later literature
(see p. 2032). Thus, the stage was set
for an extensive exploration of the metab
olism, deficiencies, excesses and require
ments of copper in man witnessed during
the past half century.
An overview of what has transpired dur
ing this period should include: 1) a vast
number of studies on copper depletion
and effects of copper supplementation in
laboratory animals; 2) recognition of natu
rally occurring deficiency of copper in farm
animals, especially cattle and sheep, in geo
graphic areas where there exists a defi
ciency of copper in the soil and vegeta
tion; 3) exhaustive analyses of the copper
content of plant and animal tissues, in
cluding those of man; 4) recognition of
states of copper deficiency in the human
infant reared on diets similar to those em
ployed in inducing copper deficiency states
in experimental animals, combined with
states of protein calorie malnutrition, in
fection and other metabolic disorders;
5) the effects of parenteral alimentation,
especially in infants suffering from devel
opmental anomalies of the alimentary tract
and post-surgical stresses; 6) recognition
of two genetically determined abnormali
ties of copper metabolism in man ( Menkes'
kinky-hair, or steely-hair, syndrome affect
ing primarily young infants and Wilson's
disease, affecting the adolescent and adult,
together with therapeutic measures for the
same; and 7) exhaustive studies of the
many copper-containing proteins distrib
uted throughout the blood and other tissues,
and their role in metabolic processes of
man and lower animals.
In the present review it is not possible
to consider the first three categories of re
search mentioned above, other than to
make reference to certain observations
which have particular relevance to the un
derstanding of copper metabolism and re
quirements of man. For additional infor
mation on the first areas of research men
tioned the reader is referred to a rather
extensive series of reviews (6, 7, 32, 71,
99, 139, 140, 185, 211, 257, 319, 461, 493,
779, 798).
COPPER IN THE HUMAN BODY
Many opinions have been expressed con
cerning the total copper content of the
human body. More than 40 years ago Chou
and Adolph (115), in studies based upon
analyses of nine organs from two adults at
autopsy, in which they found an average of
about 116 mg, estimated that the human
body contained between 100 and 150 mg
of copper. Since then estimates have been
reduced. Cartwright and Wintrobe (105)
considered 80 mg of copper to be a more
reasonable estimate for a 70-kg man. Sass-
Kortsak (666), on the basis of data of
Tipton and Cook (781), calculated a mean
of 75 mg, with a range of 50 to 120 mg.
A slightly lower estimate of 70 mg has been
given recently by Sumino et al. (762),
based upon analyses of 18 different organs
and tissues of 30 Japanese subjects, victims
of accidental deaths, 28 of whom ranged
in age from 20 to more than 60 years.
These investigators also estimated that
about one-third of body copper was in the
liver and brain combined, one-third in the
musculature, and the remaining third dis
persed in other tissues. The mean content
of copper in human liver is about \5% of
total body copper (668).
It has long been recognized that the
liver and brain contain a much higher con
centration of copper than other organs and
tissues, amounting to about 8 mg in each
of these organs ( 105). The liver content
is, in large part, related to its function as
a storage organ for copper and also as the
only site of synthesis and release of ceruloplasmin.
Copper is unevenly distributed
in the brain. While some investigators re
port very little difference in the copper
content of grey and white matter of the
cerebral cortex (102, 138, 613), others have
found a considerably higher content in the
grey than in the white matter ( 134, 138,
178, 780, 828). The substantia nigra and
locus ceruleus, both components of the
grey matter, are exceptionally rich in cop
per ( 134, 178). Possible relationships of
the pigmented nerve cells of the locus
ceruleus to their content of melanin and
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