Introduction to Human Nutrition

214 Introduction to Human Nutrition

especially when combined with feeding practices such
as cow’s milk or total parenteral nutrition. The most
frequent symptoms of copper defi ciency are anemia,
neutropenia, and bone fractures, while less frequent
symptoms are hypopigmentation, impaired growth,
increased incidence of infections, and abnormalities
of glucose and cholesterol metabolism and of electro-
cardiograms. Various attempts have been made to
relate these symptoms to alterations in copper metal-
loenzymes (see Table 9.15) and noncopper enzymes
that may be copper responsive, and to identify the role
of copper as an antioxidant, in carbohydrate metabo-
lism, immune function, bone health, and cardiovas-
cular mechanisms. Notwithstanding the rarity of

frank copper defi ciency in human populations, some

have speculated that suboptimal copper intakes over

long periods may be involved in the precipitation of

chronic diseases, such as cardiovascular disease and

osteoporosis. The pathological signifi cance of subtle

changes, in the longer term, in those systems that

respond to copper defi ciency have yet to be defi ned

for humans.

Toxicity

Acute copper toxicity in humans is rare and usually

occurs from contamination of drinking water,

beverages, and foodstuffs from copper pipes or con-

tainers, or from accidental or deliberate ingestion of

Table 9.15 Human enzymes and proteins that contain copper

Enzyme or protein Function

Cytochrome c oxidase Mitochondrial enzyme involved in the electron transport chain; reduces oxygen to water and allows
formation of ATP; activity is highest in the heart and also high in the brain, liver, and kidney
Ceruloplasmin (ferroxidase I) Glycoprotein with six or seven copper atoms; four copper atoms involved in oxidation/reduction
reactions; role of other copper atoms not fully known; scavenges free radicals; quencher of
superoxide radicals generated in the circulation; oxidizes some aromatic amines and phenols;
catalyzes oxidation of ferrous iron to ferric iron; assists with iron transport from storage to sites of
hemoglobin synthesis; about 60% of plasma copper bound to ceruloplasmin; primarily extracellular;
activity will be low during severe copper restriction
Ferroxidase II Catalyzes oxidation of iron; no other functions known; in human plasma is only about 5% of ferroxidase
activity
Hephaestin Membrane-bound ceruloplasmin homologue; probably a multicopper oxidase required for iron export
from the intestine
Monoamine oxidase Inactivates catecholamines; reacts with serotonin, norepinephrine (noradrenaline), tyramine, and
dopamine; activity inhibited by some antidepressant medications
Diamine oxidase Inactivates histamine and polyamines; highest activity in small intestine; also high activity in kidney and
placenta
Lysyl oxidase Acts on lysine and hydroxylysine found in immature collagen and elastin; important for integrity of
skeletal and vascular tissue; use of estrogen increases activity
Dopamine β-hydroxylase Catalyzes conversion of dopamine to norepinephrine (noradrenaline), a neurotransmitter; contains two
to eight copper atoms; important in brain and adrenal glands
Copper, zinc superoxide dismutase Contains two copper atoms; primarily in cytosol, protects against oxidative damage by converting
superoxide ion to hydrogen peroxide; erythrocyte concentrations are somewhat responsive to changes
in copper intake
Extracellular superoxide dismutase Protects against oxidative damage by scavenging superoxide ion radicals and converting them to
hydrogen peroxide; small amounts in plasma; larger amounts in lungs, thyroid, and uterus
Tyrosinase Involved in melanin synthesis; defi ciency of this enzyme in skin leads to albinism; catalyzes conversion
of tyrosine to dopamine and oxidation of dopamine to dopaquinone; present in eye and skin and
forms color in hair, skin, and eyes
Metallothionein Cysteine-rich protein that binds zinc, cadmium, and copper; important for sequestering metal ions and
preventing toxicity
Albumin Binds and transports copper in plasma and interstitial fl uids; about 10–15% of copper in plasma is
bound to albumin
Transcuprein Binds copper in human plasma; may transport copper
Blood clotting factors V and VIII Role in clotting and thrombogenesis; part of structure homologous with ceruloplasmin