Trace Elements
Objective: principal of
biochemistry,
functions & disorders of most common
trace
elements
Basil O M Saleh
for 2
nd
Year coll. Of
Medicine.2012.
Trace elements Tes
TES
are
expressed in µg/dl in fluids and mg/kg in tissues. The
ultraTE are expressed in ng/dl in fluids and µg/kg in
tissues. They are essentials when the sign and
symptoms induced by an element deficiency are
reversed only by adequate supply of that element. TEs
are
important
or
essential
for
many
critical
biochemical
processes,
deficiencies
are
often
associated with decreased activities of the Enzymes Es
that require TEs for optimal activity. Function can be
restored by dietary replacement, but must be in care
from toxicity. A chemical element required in minute
quantities by an organism to maintain proper physical
functioning.
Dose-Effect
relationships:
In low intake of an element the biological function of
humans
decreased(determintal
effects),
with
continues supply or intake of element the biological
functions improved with approaching the pletaue
region(constant optimal human function even with
increased element concentrations), but with increased
element levels the biological functions decline(Toxicity
region, which depend on element and its chemical
structure
in
the
diet).
Iron
Fe:
I
ron is widely distributed throughout the human
body with≈3-5 g in 70 kg human body,1. in Hb of
RBCs(2g),2. storage
iron
in
the form
of
Ferritin
and hemosiderin.Ferritin is found in
all tissues mainly hepatocytes and in bone
marrow and spleen. This stored iron ,may be
first depleted in iron deficiency states. This
stored iron is ready for Hb and other heme
proteins formation and in this form iron shielded
from oxidative toxicity(ionic Fe+3 is toxic
;prooxidant).
3.Tissue iron, this repressents the amount of iron
in enzymes or
cofactors for enzymes;
peroxidases, cytochromes(heme proteins), many
CAC enzymes. 4. Myoglobin resembles Hb but
monomer and deals with storage of
O2
in
muscles.
Transferrin
is
the
carrier
protein(transporter) of iron in blood and
intracellular compartments. Dietary requirement
is ≈1mg/day to compensate that lost from body,
mainly
in
feces.
Excretion
increased
in
menstrauting women 20 mg/cycle.
Intestine is the
regulatory step
in homeostasis
of iron. In iron deficency(decreased body iron
content), the amounts of the intestinal absorbed iron
and their release into the circulation are increased to
compensate the body’ s deficiency. The inverse in case
of iron overload(increase of iron body content), most
of the absorbed iron is sloughed during the sheding of
the enterocytes.
Functions of iron
mainly in transporting(as
part of Hb) of O2 from lung to the tissues, and
returing of CO2 to the lung excretion in ventilation.
Iron in Hb must be in Fe +2, if Fe+3 is nonfunctional
Hb= metHb. Peroxidase and catalase to remove of
H2O2 and free radical as H2O. Thyroperoxidase
involved
in
formation
of
thyroid
Hs.
Disorders:
Iron deficency; Anemia
. It is the most
common
disease,
affects
≈15%
of
worldwide
population.
Menstrating, pregnant,lactating women, neonate(low
milk iron content), children, and adolescents at higher
risk of iron deficiency. Increased blood loss and low
dietary iron intake= decreased iron body stores and so
iron deficiency(anemia): investigations: low serum
iron(in most but not all), increase Total Iron Body
Capacity
TIBC(unoccupied
sites
on
transferrin),
decrease RBCs, MCHC and microcytic anemia. But
now the more sensitive and reliable test in iron
deficency is serum
ferritin.
Iron overload
:
secodary
in poisoning of
iron
by
oral
ingestion
or
parentral
administration. In Primary, hemochromatosis
and hemosiderosis. In iron overload, serum iron
increased and TIBC is decreased, serum ferritin is
not
reliable
in
this
disorder.
Primary Hemochromatosis
: overload
of iron due to genetic defect in which there is
increased absorption of intestinal iron even with
normal dietary content. Symptoms: which are due to
toxic accumulation of iron in organs are: D M,
bronzing of skin and cirrhosis. Hemosiderosis: iron
overload,but without tissues injuries(due to excess
iron medication).
Copper
Cu:
I
s an important element found in +1 and +2. it is
found
in
meats;liver
and
kidney,also,
in
shellfish,nuts, whole grain cereals…
. Lower
amounts in dairy products;cow΄ s milk and white
meats. Absorbed Cu is transported to liver by
albumin,
where
it
incorporated
in
cupproenzymes and proteins, the major one is
apoceruloplasmin+Cu= ceruloplasmin. 2/3 of
body Cu (80-100 mg) in skeleton and muscle, in
blood
90
%
of
Cu
incorporated
in
ceruloplasmin(glycoprotein). Excretion mainly by bile-
intestine(0.5-2 mg)=feces,so in bile obstruction=
increased
of
Cu
accumulation.
Functions:
Essential component of cuproenzymes
and structural proteins: 1.Cytochrome C oxidase of
respiratory chain= ATP production, 2. lysyl oxidase
involved in structural proteins;collagen and elastin, so
important in connective tissues formation;skin,
skeleton, 3. Dopamine hydroxylase and monoamino
oxidases
involved
in
catacholamine
synthesis(adrenaline and noradrenaline) so important
for CNS function,
4.
Tyrosinase involved in melanin synthesis 5. IC and
EC superoxid dismutase SOD involved in antioxidant
defence. 5. Ceruloplasmin (ferroxidase) is important in
in normal iron metabolism and Hb formation.
Disorder
is
Menkes΄syndrome
recessive X-linked
genetic defect in copper transport from intestinal
mucosa(normal
absorption),
so
Cu
cannot
be
transported to liver and results in Cu deficiency=
mental defect, failure to thrive, diminshed Cu
containing enzymes, connective tissues abnormalities,
kinky hair and early death. Anemia due to defect in
normal metabolism of Iron.
Wilson ΄s disease
.. Cu overload disorder.
It is a
utosomal genetic defects in incorporation of Cu
into
apoceruloplasmin=accumulation
of
the
abosorbed,transported Cu into liver(not exported into
circulation from liver), kidney, cornea, brain… .=liver
cirrhosis, brain lesions, Kayser Fleischer rings; low
S.Cu(˂50 µg/dl), high urinary Cu excretion, low
S.ceruloplasmin(˂200 mg/l). Liver biopsy: normally Cu
8-40
µg/kg,
in
this
disease
˃250µg/kg.
S.Ceruloplasmin is acute phase reactant so increased
in acute inflammation and OC pills.
Zinc
Zn
:
it found in meat, fish and dairy
products. RDA 8-11 mg/day, pregnant and children
increase requirement. Absorbed Zn transported to
liver bound to albumin and α2-macroglobulin.
Excretion mainly bile-intestine.
Zn
is an important
cofactor for ˃300 enzymes. Also, integral component
of important enzymes;ALP, Alcohol DH, carbonic
anhydrous( the latter predominant in RBCs) .Zn
enzymes are essential for DNA and RNA(polymearses
enzymes so essential for growth,wound healing),
integrity of connective tissues, reproductive function,
the immune system and protection from free radical
damage(SOD). Insufficient dietary Zn is important
cause of deficiency, PO4
and fiber=decrease Zn
absorption.
Zn
deficiency;
clinical
features:
growth
retardation(dwarfism), skin lesions, alopecia, slow
wound healing, diarrhea, impotence, and tendency to
infections(decrease
T-cell
function).
Acrodermatitis
Enteropathica
characterized by low blood Zn;dermatitis,alopecia and
diarrhea.
Chromium
Cr
RDA is ≈ 50-200µg/d. forms Cr +3 and +6, the Cr+6 is
toxic(oxidant,damage
tissue
damage).
Processed
meats,whole grain products, green beans are good
sources, but fruit and dairy products are not. After
intestinal absorption transported by transferrin with
equal affinity to Fe+3.It is essential as it is a potent
activator of Insulin, Cr deficiency is associated with
Insulin resistance and impaired glucose tolerance and
Cr supplementation improved glucose tolerance and
decreased
total
cholesterol
in
Type
2
DM.
Cr +6 is carcinogenic; contamination(leather tanning
and dyestuff industries) with this ion =increased
incidence of lung cancer, dermatitis and skin ulcers.
Selenium
Se
It has essential functions: cofactor for glutathione
peroxidase
GPX(Antioxidant
enzymes)
and
iodothyronine
deiodinase(ENZYMES
of
thyroid
hormones
synthesis)
.
It
has
antioxdant
function(component of GPX), and involved in thyroid
Hs metabolism(T4→T3).
Se
soil contents is important in incidence of element
deficiency. Deficiencies Disorders are
Keshan disease
is endemic cardiomyopathyin childern and young
adults,
Kashin-Beck disease
it is severe arthritis,
Thyroid diseases
: endemic goiter(hypothyroidism with
low T3),
Floride F
is important in preventing dental
caries, incorporated into bone crystal, increasing bone
mass in vertebrae.
F
from GIT→bone+teeth. Renal
excretion is major route of excretion. Measurement
by Ion-selective electrodes. Sources by addition of F
to water and sugar and salt. Toxicity mottling of teeth
and calcifications of soft tissues.
Manganese
Mn
Present in +2 and+3. it is activator for several
enzymes;
arginase(urea
cycle),
pyruvate
carboxylase(gluconeogenesis), and SOD. Its deficiency
features is rare, but may be seizures and eplipsy.
Cobalt Co
It is essential for human only as integral component of
vit.B12 (cobalmin), however, B12 must be supplied as
that in diet and Co cannot interacts with pool of body
vit.B12. The physiological signs of severe vitamin B
12
deficiency are
anemia, spinal cord
.
Iodine
This trace element has one known function in higher
animals and humans; it is a constituent of
s (
, T
4
) and triiodothyronine (T
3
).
iodine prevented
, enlagement of thyroid gland,
and increased iodine intake was associated with
decreased endemic
, the arrested physical
and mental development caused by the lack of
hormone.
Today,
the
consequences
of
still are a major public health problem in
the world.