conspectus of researchon copper metabolism and requirements

COPPER METABOLISM AND REQUIREMENTS OF MAN 2003
occur in mother and infant. Maternal levels
of serum copper decrease to non-pregnant
levels during the first 2 weeks postpartum
(100, 206, 293, 294, 561). This is ascribed
to the abrupt cessation of estrogenic
stimuli for ceruloplasmin synthesis. At the
same time, infant levels of serum copper,
which are lower at birth than at any pe
riod of life, promptly increase until adult
levels are attained between the 2nd and
3rd months of life (91, 293, 325, 690).
This is due almost entirely to increased
synthesis of ceruloplasmin by the infant's
liver. In other studies, estimates of the age
at which adult values are reached vary
from about 3 to 6 months (338, 494, 638),
to 9 to 12 months (411, 606). Several in
vestigators report that after adult serum
copper levels are attained during the first
2 or 3 months of life, these levels rise sig
nificantly above normal after the 4th
month (758 ) or during the 2nd year of life
(131, 362, 656), and then gradually de
cline to adult levels at puberty. Sass-
Kortsak (666) gives mean values of 140,
129 and 117 /¿g/100ml for 2-, 6- and 10year
old children. Hrgovic and Hrgovic
(362) record mean values of 179, 151, 133
and 111 Mg/100 ml for age groups 0 to 5,
5 to 10, 10 to 15 and 15 to 18 years. No
sex differences are apparent until puberty,
after which the effect of female estrogens
on increased serum copper levels becomes
manifest. Similar observations have been
reported by other investigators (573, 776).
Neither the reason for, nor the significance
of these fluctuations in early life has been
elucidated.
Immunological methods have identified
an apoceruloplasmin in newborn infant
plasma in concentrations similar to that
of ceruloplasmin in the adult, thus indi
cating that only the inability to charge the
apoprotein with its normal complement of
copper is underdeveloped at birth (714).
Similar observations have been made in
studies with piglets (108, 109, 523).
On the other hand, remarkable changes
occur in the liver of the newborn, which
contains about one-half the copper in the
body and a concentration, in terms of cop
per per unit weight, 5 to 10 times that of
the adult liver (843, 846). A large com
ponent of this copper is bound to hepatic
initochondrocuprein, first isolated and de
scribed by Porter et al. (615). This cop
per-storage protein, found only in the fetus
and newborn, is thought to represent a
copper-rich polymerized form of metallothionein
which sequesters copper prior to
birth (611, 614). Liver copper rapidly
disappears during the first few months of
life (69, 627, 846), releasing copper for
ceruloplasmin synthesis and the general
needs of tissues of the rapidly growing in
fant. The ceruloplasmin synthesized by the
neonate is identical to that of the adult
(870). Thus there is a logical explanation
for the early reports of Kleinman and
Klinke (414) and Morrison and Nash
(538) that the concentration of copper in
the liver of newborn and young infants is
6- to 18-fold that of adults.
Although copper and ceruloplasmin
blood levels are lower in the newborn than
at any other period of life, the copper con
centration in fetal and neonatal organs and
tissues is much higher than in the adult
(207, 248, 414, 565, 781). The studies of
Fazekas (207), based upon analysis of 29
different organs and tissues of 109 fetuses
and full-term infants of varied gestational
age, indicate that in addition to liver, the
concentration of copper in muscle, skin,
adrenal glands and thyroid is particularly
high compared to that of adults. The cop
per content of the placenta is also rather
high (525, 605). The high concentrations
of copper in organs and tissues of the
newborn decrease gradually to normal
levels during the first year of postnatal life
(69, 248, 565).
The unusually high concentrations of
copper in liver and other tissues of the
neonate appear to represent a reserve to
assure an adequacy of copper for syn
thesis of ceruloplasmin and other coppercontaining
proteins to meet metabolic
needs for hematopoietic, maturational and
other functions in the rapidly growing in
fant and adolescent prior to puberty. These
changes naturally create difficulties in
reaching definitive conclusions concerning
the dietary requirements during these early
years of human development. For other
details concerning the role of copper in
pregnancy, and in prenatal and postnatal
development, the reader is referred to a
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