conspectus of researchon copper metabolism and requirements

1996 KARL E. MASON
enterohepatic circulation of copper, con
sidered unlikely on the basis of the macromolecular
complexes of copper predomi
nating in the gall bladder bile (266), now
justifies more critical study.
More recently evidence has been found
that the mechanism of copper excretion
may involve its complexing with taurochenodeoxycholate
in the liver, thereby
preventing its reabsorption from the upper
intestine, with subsequent splitting of the
complex in the lower intestine where reabsorption
of the bile acid but not of cop
per may take place (454). Other evidence,
also based upon bile from T-tubes, sug
gests that orally administered 04Cu be
comes combined with conjugated bilirubins
(503 ). It is obvious that there is still much
more to be learned about the binding of
copper in bile and its possible reabsorbability.
Salivary excretion
Little or no attention had been given to
the presence of copper in saliva until 1952
when Dreizen et al. ( 170) reported finding
in the whole saliva of 14 normal humans
(48 samples) a mean copper concentration
of 25.6 /Ag/100 ml. In general agreement
with these findings are those of De Jorge
et al. (157) based on 40 normal, fasting
subjects, giving a mean value of 31.7 /¿g/
100 ml, and of Gollan et al. (264) based on
18 normal subjects and providing a mean
value of 29 /¿g/100ml. The ' copper of
saliva is in the labile form, since reactions
for ceruloplasmin are negative (157). If
one considers the daily output of saliva to
be 1.5 liters (range 1-2 liters), the total
daily excretion of copper would amount to
from 0.38 to 0.47 mg, on the basis of the
data recorded above. There is also evi
dence that the copper-binding substances
in saliva retain their activity after transit
through the stomach to the site of absorp
tion in the small intestine. De Jorge et al.
(157) also report mean copper values of
submaxillary, parotid and pancreas re
moved from 10 postmortem cases as 1.43,
0.55 and 0.85 mg/100 g dry weight of tis
sue, respectively.
Gastrointestinal excretion
In his pioneer studies on the metabolism
of copper in man, Van Ravensteyn (805)
found an average copper concentration of
0.023 mg/100 ml (range 0.01-0.04 mg/100
ml) in gastric juice of eight normal sub
jects. Some 27 years later, other data were
provided by Gollan et al. (265) who, in
four normal subjects, found a mean con
centration of 0.034 mg/100 ml (range 0.02-
0.96 mg/100 ml). In the latter studies
gastric juice free of swallowed saliva and
nasopharyngeal secretions was aspirated
from fasting subjects, and particulate mat
ter was removed by centrifugation at 2,000
X g for 20 minutes. Accepting the values
reported by Gollan et al. (265), employing
exacting collecting and analytical pro
cedures, and considering current estimates
that the daily volume of gastric secretions
approximates 3 liters (range 2-4 liters), it
can be calculated that the gastric mucosa
secretes approximately 1.0 mg/day.
The only recorded study of duodenal
secretion of copper is that of Gollan (263 ).
Normal and secretin-stimulated aspirates
of the duodenum, obtained from fasting
normal subjects through a tube positioned
such as to exclude gastric contents (and
presumably to also exclude bile and pan
creatic secretions) indicates the presence
of copper-binding substances of low molec
ular weight such as also found in saliva
and gastric juice. Gollan presents evidence
that the latter binding substances retain
their activity after transit through the
stomach to the site of absorption in the
small intestine. He also postulates that
these secretions, through their capacity to
solubilize the metal at an alkaline pH, may
enhance the availability of copper for ab
sorption.
Relatively little attention has been given
to, or estimates made of, the amount of
copper released into the feces via the ex
tensive dehiscence of epithelial cells of the
intestinal mucosa. In these cells there is a
considerable amount of copper bound to
metallothionein or metallothionein-like pro
teins, functioning in copper storage and in
protection against excess copper intake.
Considering that the absorptive cells lining
intestinal villi are replaced every 5 to 6
days in man (475), this contribution of
copper to the intestinal contents and to
the fecal output may be quite significant,
since it is thought to be nonabsorbable
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