Minerals and Trace Elements 219selenium-defi cient host, but also when isolated and
injected into selenium-replete animals. A coxsackie
virus has been isolated from the blood and tissues of
patients with Keshan’s disease and the infection may
be responsible for the cardiomyopathy of that disease.
It has been speculated that similar events linked with
other RNA viruses may explain the emergence of new
strains of infl uenza virus in China and the postulated
crossing-over of the human immunodefi ciency virus
(HIV) to humans in the selenium-defi cient popula-
tion of Zaire. Many human viral pathogens (e.g., HIV,
coxsackie, hepatitis, and measles viruses) can synthe-
size viral selenoproteins and, thereby, lower the sele-
nium available to the host. In any event, selenium
defi ciency is accompanied by loss of immunocompe-
tence, with the impairment of both cell-mediated
immunity and B-cell function. Covert suboptimal
selenium status may be widespread in human popula-
tions, as selenium supplementation in subjects
considered to be selenium replete had marked immu-
nostimulant effects, including increased proliferation
of activated T-cells. Such immunostimulant effects or
the production of antitumorigenic metabolites may
explain the lowering of cancer incidence, particularly
prostate cancer, after selenium supplementation in
selenium-replete subjects (those who already had
maximized selenoenzyme activity). Other proposed
mechanisms for a cancer chemoprotective effect of
selenium include antioxidant protection and reduc-
tion of infl ammation; inactivation of protein kinase
C; altered carcinogen metabolism; reduction in DNA
damage, stimulation of DNA repair (p53), and altera-
tion in DNA methylation; cell cycle effects; enhanced
apoptosis and inhibition of angiogenesis. Further
evidence for any chemoprotective effect of selenium
against cancer should arise from the Selenium and
Vitamin E cancer Prevention Trial (SELECT), which
is a large randomized controlled trial investigating the
effi cacy of selenium (200 μg of l-selenomethionine)
and vitamin E (400 IU, dl-α-tocopherol acetate) alone
and in combination for the prevention of prostate
cancer in over 35 000 healthy men in 435 sites in the
USA, Puerto Rico, and Canada and which should
report sometime after 2008.Table 9.18 Selenoproteins
Selenoprotein Function
Glutathione peroxidases (GPx1, GPx2, GPx3, GPx4;
cystolic, gastrointestinal, extracellular and
phospholipid hydroperoxide, respectively)
Antioxidant enzymes: remove hydrogen peroxide, and lipid and phospholipid
hydroperoxides (thereby maintaining membrane integrity, modulating
eiconsanoid synthesis, modifying infl ammation, and likelihood of propagation of
further oxidative damage to biomolecules, such as lipids, lipoproteins and DNA)
(Sperm) mitochondrial capsule selenoprotein Form of glutathione peroxidase (GPx4): shields developing sperm cells from
oxidative damage and later polymerizes into structural protein required for
stability/motility of mature sperm
Iodothyronine deiodinases (three isoforms) Production and regulation of level of active thyroid hormone, T 3 , from thryoxine T 4
Thioredoxin reductases (three isoforms) Reduction of nucleotides in DNA synthesis; regeneration of antioxidant systems;
maintenance of intracellular redox state, critical for cell viability and proliferation;
regulation of gene expression by redox control of binding of transcription factors
to DNA
Selenophosphate synthetase, SPS2 Required for biosynthesis of selenophosphate, the precursor of selenocysteine, and
therefore for selenoprotein synthesis
Selenoprotein P Found in plasma and associated with endothelial cells; appears to protect
endothelial cells against damage from peroxynitrite
Selenoprotein W Needed for muscle function
Prostate epithelial selenoprotein (15 kDa) Found in epithelial cells of ventral prostate; seems to have redox function
(resembles GPx4), perhaps protecting secretory cells against development of
carcinoma
DNA-bound spermatid selenoprotein (34 kDa) Glutathione peroxidase-like activity; found in stomach and in nuclei of spermatoza;
may protect developing sperm
18 kDa selenoprotein Important selenoprotein, found in kidney and large number of other tissues;
preserved in selenium defi ciency
Reprinted with permission from Elsevier (Rayman, MP Lancet, 2000, 356 , pp. 233–241).