210 Introduction to Human Nutrition
generally assumed that the body has no specifi c zinc
reserve and is dependent on a regular supply of the
element.
With essential roles in many fundamental cellular
processes (see below), it is not surprising that whole-
body zinc content is tightly controlled. Zinc in foods
is absorbed via a carrier-mediated transport process,
which under normal physiological conditions appears
not to be saturated. Zinc is absorbed throughout the
small intestine. Proximal intestinal absorption is effi -
cient, but it has a large enteropancreatic circulation;
the net intestinal absorption of zinc is achieved by the
distal small intestine. Zinc is transported in the plasma
by albumin and α 2 -macroglobulin, but only 0.1% of
body zinc is found in plasma. Body zinc content is
regulated by homeostatic mechanisms over a wide
range of intakes by changes in fractional absorp-
tion (normally 20–40%) and urinary (0.5 mg/day)
and intestinal (1–3 mg/day) excretion. For example,
during periods of low zinc intake, absorption is
enhanced and secretion of endogenous zinc into the
gastrointestinal lumen is suppressed. In contrast, high
zinc intake is associated with decreased absorption
and enhanced secretion of endogenous zinc. Within
cells, fl uctuations in zinc content are modulated
by changes in the amount of the metal associated
with the storage protein metallothionein but there
is a large number and variety of zinc homeostatic
proteins found throughout cells. Although zinc
transporters are very important for generating and
maintaining zinc gradients across membranes and
within cellular compartments, little is known about
many aspects of their functions and regulatory modes
of action.
The bioavailability of dietary zinc depends on
dietary enhancers and inhibitors and host-related
factors (Table 9.12). Diets can be roughly classifi ed as
having a low, medium, or high bioavailability, accord-
ing to the content of zinc, phytate, and animal protein.
From a mixed animal and plant product diet, 20–30%
zinc absorption can be expected. The lowest absorp-
tion, 10–15%, is seen from diets prevalent in develop-
ing countries that are based on cereals and legumes
with a high phytate content and with negligible
amounts of animal protein.
Metabolic function and essentiality
Zinc has three major groups of functions in the
human body: catalytic, structural, and regulatory.
Most biochemical roles of zinc refl ect its involvement
in the folding and activity of a large number (up to
10%) of proteins and over 100 different zinc metal-
loenzymes have been identifi ed, including RNA
nucleotide polymerase I and II, alkaline phosphatase
and carbonic anhydrases. Important structural roles
for zinc are in the zinc fi nger motif in proteins, but
also in metalloenzymes [e.g., copper/zinc superoxide
dismutase (Cu/Zn-SOD)]. Zinc is also required by
protein kinases that participate in signal transduction
processes and as a stimulator of transacting factors
responsible for regulating gene expression. Zinc plays
an important role in the immune system and, though
not a redox-active transition metal, is an antioxidant
in vivo.
Defi ciency symptoms
The clinical manifestations of severe zinc defi ciency
in humans are growth retardation, sexual and skeletal
immaturity, neuropsychiatric disturbances, derma-
titis, alopecia, diarrhea, increased susceptibility to
infections, and loss of appetite. Many of these fea-
tures, by and large, represent the dependence on zinc
of tissues with a high rate of turnover. However, severe
zinc defi ciency in humans is rare, and more interest
has been focused on marginal zinc defi ciency. This is
more diffi cult to diagnose and often occurs with other
micronutrient defi ciencies including iron. The current
understanding of zinc defi ciency is largely based on
responses to zinc supplementation. Zinc supplemen-
tation has been reported to stimulate growth and
development in infants and young children, and
reduce morbidity (diarrhea and respiratory infec-
tions) in children, particularly in developing coun-
tries and can increase both innate and adaptive
immunity. In women, low serum zinc concentration
during pregnancy was found to be a signifi cant
Table 9.12 Factors affecting zinc absorption
Increased absorption Decreased absorption
Physiological factors
Depleted zinc status Replete zinc status
Disease state (acrodermatitis enteropathica)
Dietary factors
Low zinc intake High zinc intake
Certain organic acids Phytate
Certain amino acids Certain metals
Human milk