Minerals and Trace Elements 213of copper pipes, and municipal water supplies can
contain appreciably higher concentrations. The taste
threshold of copper ranges from 1 to 5 mg Cu/l, pro-
ducing a slight blue–green color at concentrations
5 mg/l copper. Acute copper toxicity symptoms,
mainly nausea and gastrointestinal irritation, can
occur at concentrations of >4 mg/l copper.
Absorption, transport, and
tissue distribution
About 50–75% of dietary copper is absorbed, mostly
via the intestinal mucosa, from a typical diet. The
amount of dietary copper appears to be the primary
factor infl uencing absorption, with decreases in the
percentage absorption as the amount of copper
ingested increases. High intakes of several nutrients
can also infl uence copper bioavailability. These
include antagonistic effects of zinc, iron, molybde-
num, ascorbic acid, sucrose, and fructose, although
evidence for some of these is mainly from animal
studies. Drugs and medication, such as penicillamine
and thiomolybdates, restrict copper accumulation
in the body and excessive use of antacids can inhibit
copper absorption. Although high intakes of sulfur
amino acids can limit copper absorption, absorption
of copper is promoted from high-protein diets.
Ionic copper can be released from partially digested
food particles in the stomach, but immediately forms
complexes with amino acids, organic acids, or other
chelators. Soluble complexes of these and other highly
soluble species of the metal, such as the sulfate or
nitrate, are readily absorbed. Regulation of absorp-
tion at low levels of copper intake is probably by a
saturable active transport mechanism, while passive
diffusion plays a role at high levels of copper intake.
Regulation of copper absorption is also effected via
metallothionein, a metal-binding protein found in
the intestine and other tissues. Metallothionein-
bound copper in mucosal cells will be lost when these
cells are removed by intestinal fl ow. The major regula-
tor of copper elimination from the body, however, is
biliary excretion. Most biliary copper is not reab-
sorbed and is eliminated in the feces. The overall
effect of these regulatory mechanisms is a tight
homeostasis of body copper status. Little copper is
lost from the urine, skin, nails, and hair.
After absorption from the intestinal tract, ionic
copper (2) is transported tightly bound to albumin
and transcuprein to the liver via the portal blood-
stream, with some going directly to other tissues,
especially the kidney. Hepatic copper is mostly incor-
porated into ceruloplasmin, which is then released
into the blood and delivered to other tissues. Uptake
of copper by tissues can occur from various sources,
including ceruloplasmin, albumin, transcuprein, and
low molecular weight copper compounds. Chaperone
proteins are then thought to bind the copper and
transfer bound copper across the cell membrane to
the intracellular target proteins, for example cyto-
chrome c oxidase. The ATPase proteins may form part
of the transfer process.
The body of a healthy 70 kg adult contains a little
over 0.1 g of copper, with the highest concentrations
found in the liver, brain, heart, bone, hair, and nails.
Over 25% of body copper resides in the muscle, which
forms a large part of the total body tissue. Much of
the copper in the body is functional. Storage of copper,
however, is very important to the neonate. At birth,
infant liver concentrations are some fi ve to 10 times
the adult concentration and these stores are used
during early life when copper intakes from milk
are low.Metabolic functions and essentiality
Copper is a component of several enzymes, cofactors,
and proteins in the body. These enzymes and proteins
have important functions in processes fundamental
to human health (Table 9.15). These include a require-
ment for copper in the proper functioning of the
immune, nervous and cardiovascular systems, for
bone health, for iron metabolism and formation of
red blood cells, and in the regulation of mitochon-
drial and other gene expression. In particular, copper
functions as an electron transfer intermediate in
redox reactions and as a cofactor in several copper-
containing metalloenzymes. As well as a direct role in
maintaining cuproenzyme activity, changes in copper
status may have indirect effects on other enzyme
systems that do not contain copper.Defi ciency symptoms
Owing to remarkable homeostatic mechanisms, clini-
cal symptoms of copper defi ciency occur in humans
only under exceptional circumstances. Infants are
more susceptible to overt symptoms of copper defi -
ciency than are any other population group. Among
the predisposing factors of copper defi ciency are
prematurity, low birth weight, and malnutrition,