CCHM312-LEC
WEEK 13: TRACE ELEMENTS
FINALS I SECOND SEMESTER
TRACE ELEMENTS
Trace elements = small amount
• An element is considered essential if a deficiency impairs
a biochemical or functional process, and replacement of
the element corrects this impairment.
o Decreased intake, impaired absorption, increased
excretion, and genetic abnormalities are all examples
of conditions that could result in deficiency of one or
several trace elements
• Any element that is not considered essential is classified
as nonessential. Nonessential trace elements are of
medical interest primarily because many of them are toxic.
o Not really required, no clinical significance, considered
as toxic
NOTE
• Toxicity and deficiency can be seen in essential trace
elements
• Nonessential – purely toxicity
METHODS AND INSTRUMENTATION
• Atomic Absorption Spectrometer (AAS)
• Atomic Emission Spectrometer (AES)
• Flame Atomic Absorption Spectroscopy (FAAS)
• Graphite Furnace Atomic Absorption Spectroscopy
(GFAAS)
• Inductively Coupled Plasma Atomic Emission
• Spectroscopy (ICP-AES)
• Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
ALUMINUM
• Crystalline silver white ductile metal
• Most abundant metal earth’s crust (~8%)
• It is always found combined with other elements
• such as oxygen, silicon, and fluorine
• Aluminum as the metal is obtained from aluminum-
containing minerals.
• Good conductivity of heat & Electricity
o ease of welding, tensile strength, light weight, and
corrosion-resistant oxide coat, aluminum is applicable
to a wide variety of industrial and household uses
• Aluminum is used for beverage cans, pots and pans,
airplanes, siding and roofing, and foil
• Aluminum compounds have many different uses, for
example, as alums in water treatment and alumina in
abrasives and furnace linings
• They are also found in consumer products such as
antacids, astringents, buffered aspirin, food additives,
cosmetics, and antiperspirants.
• Aluminum absorbs in our body through ingestion (orally),
inhalation and parenterally. There is no indication of
dermal absorption
• The absorption efficiency is dependent on chemical form,
particle size (inhalation), and concurrent dietary exposure
to chelators such as citric acid or lactic acid.
o Chelators – compounds which binds, in order to render
readily excretable
• After a relatively quick uptake of aluminum into the
intestinal walls, its passage into the blood is much slower.
o Once aluminum are now in blood circulation, transport
mechanism become slower
• In plasma, aluminum is bound to carrier proteins such as
transferrin.
• Aluminum binds to various ligands in the blood and
distributes to every organ, with highest concentrations
ultimately found in bone (~50% of the body burden) and
lung tissues (~25% of the body burden)
o Aluminum levels in lungs increase with age
• Urine accounts for 95% of aluminum excretion with 2%
eliminated in the bile
A. HEALTH EFFECTS & TOXICITY
• Toxicity is not well understood, though aluminum has been
shown to interfere with a variety of enzymatic processes
• Encephalopathy
o administration of aluminum to experimental animals is
known to produce encephalopathy similar to that seen
in Alzheimer disease in man
• Aluminum-containing over-the-counter oral products are
considered safe in healthy individuals at recommended
doses, some adverse effects have been observed
following long-term use in some individuals
Gonzales & Cenina & Mamorno
• Industrial exposure
o Workers who breathe large amounts of aluminum dusts
can have lung problems, such as continuous coughing
or changes that show up in chest X-rays
• Signs and symptoms of aluminum toxicity include
o encephalopathy (stuttering, gait disturbance,
myoclonic jerks, seizures, coma, and abnormal EEG);
o osteomalacia or aplastic bone disease (painful
spontaneous fractures, hypercalcemia, and tumorous
calcinosis);
o proximal myopathy;
o increased risk of infection;
o microcytic anemia;
o increased left ventricular mass and decreased
myocardial function
• Aluminum toxicity occurs in people with renal
insufficiencies who are treated by dialysis with aluminum
contaminated solutions or oral agents that contain
aluminum
• The clinical manifestations of aluminum toxicity include
o anemia, bone disease, and progressive dementia with
increased concentrations of aluminum in the brain
• Prolonged intravenous feeding of preterm infants with
solutions containing aluminum is associated with impaired
neurologic development
B. LABORATORY:
• Aluminum is primarily measured using ICP-MS or GFAAS
• Accurate measurements are often complicated by the
increased risk of environmental contamination of
specimens
• Urine and serum levels are useful in determining toxic
exposures, monitoring exposure overtime, and monitoring
chelation therapy
ARSENIC
• ubiquitous element displaying both metallic and non-
metallic properties
• Earth’s crust (1.5-2.0 mg/kg)
• For most people, food is the largest source of arsenic
exposure (about 25-50 μg/d), with lower amounts coming
from drinking water and air
• Anthropogenic sources (production of metals, burning of
coil, fossil fuels, timber and its use in agriculture) release
three times more of arsenic than natural sources
• Mostly industrial purposes
o The main current use of arsenic is as a wood
preservative. Other current and past uses of arsenic
include pesticides, pigments, poison gases,
ammunition manufacturing, semiconductor processing,
and medicines.
A. HEALTH EFFECTS & TOXICITY
• The relation of clinical signs and symptoms to arsenic
exposure depends on the duration and extent of the
exposure to inorganic and methylated species of arsenic,
as well as the underlying clinical status of the patient.
• For acute arsenic exposure
o gastrointestinal (nausea, emesis, abdominal pain, and
rice water diarrhea),
o bone marrow (pancytopenia, anemia, and basophilic
stippling),
o cardiovascular (ECG changes),
o central nervous system (encephalopathy and
polyneuropathy),
o renal (renal insufficiency and renal failure), and
o Liver/hepatic (hepatitis) systems
• For chronic arsenic exposure, systems and symptoms may
include
o dermatologic (Mees’ lines (nail), hyperkeratosis,
hyperpigmentation, and alopecia),
o hepatic (cirrhosis and hepatomegaly),
o cardiovascular (hypertension and peripheral vascular
disease [PVD]),
o central nervous system (“socks and glove” neuropathy
and tremor),
o malignancies (squamous cell, hepatocellular, skin,
bladder, lung, liver and renal carcinomas).
• Chronic arsenic exposure has been shown to cause
blackfoot disease, a severe form of PVD which leads to
gangrenous changes
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 WEEK 13: TRACE ELEMENTS
• The white powder of arsenic trioxide is odorless, tasteless,
and one of the most common poisons in human history.
• Doses of 0.01-0.05 g produce toxic symptoms.
• The lethal dose is reported to be between 0.12-0.3 g;
however, recoveries from higher doses have been
reported.
• Immediate treatment of expected exposure consists of
lavage and use of activated charcoal to reduce arsenic
absorption.
• The most effective antidotes for arsenic poisoning are the
following chelating agents:
o dimercaprol (a.k.a British anti-Lewisite), penicillamine,
and succimer.
• In 2000, the US FDA approved the use of arsenic trioxide
for the treatment of acute promyelocytic leukemia, which is
diagnosed in approximately 1,500 people in the United
States every year
NOTE
• The main routes of exposure are ingestion of arsenic
containing foods, water, and beverages or inhalation of
contaminated air
• Organic forms of arsenic such as arsenocholine and
arsenobetaine are commonly found in fish and seafood,
are considered relatively non-toxic, and are cleared rapidly
(1-2 days).
• Inorganic species of arsenic are highly toxic and occur
naturally in rocks, soil, and groundwater.
o They are also found in many synthetic products,
poisons, and industrial processes
• Methylated species are intermediate in toxicity and arise
primarily from metabolism of inorganic species, but small
amounts may arise directly from food.
o Organic methylated arsenic compounds such as
monomethylarsonic acid (MMA) and dimethylarsenic
acid (DMA) are formed by hepatic metabolism of
As(3+) and As(5+).
o The methylated inorganic forms are considered less
toxic than As(3+) and As(5+); however, they are
eliminated slowly (1-3 week).
B. LABORATORY:
• ICP MS, GFAAS or HG AAS
• arsenic is best detected by urine (specimen of choice) due
to the short half-life of arsenic in blood
• Arsenic speciation is desired, a separation method is
employed either online or offline prior to metal analysis
CADMIUM
• Soft, bluish white metal which is easily cut with a knife
• Principal industrial uses of cadmium include manufacture
of pigments and batteries, as well as in the metal-plating
and plastics industries
• the burning of fossil fuels such as coal and oil and the
incineration of municipal waste materials constitute the
largest sources of airborne cadmium exposure, along with
zinc, lead, and copper smelters in some locations
NOTE
• Absorption of cadmium is higher in females than in males
due to differences in iron stores.
o Since it has affinity to iron molecule
• The absorption of inhaled cadmium in air (airborne) is 10%
to 50% with gastrointestinal absorption of cadmium
estimated to be 5%
• The absorption of cadmium in cigarette smoke is 10-50%
and smokers of tobacco products have about twice the
cadmium abundance in their bodies as nonsmokers
o Smokers high amount of cadmium
• For nonsmokers, the primary exposure to cadmium is
through ingested food
• About 90% of ingested cadmium is excreted in the feces
due to the low absorbance of cadmium from the gut.
• Kidney → where cadmium mostly accumulate, which
caused proteinuria
A. TOXICITY
• has no known role in normal human physiology.
• Toxicity is believed to be a result of protein-Cd adducts
causing denaturation of the associated proteins, resulting
in a loss of function
• Ingestion of high amounts of cadmium may lead to a rapid
onset with severe nausea, vomiting, and abdominal pain
• Renal dysfunction is a common presentation for chronic
cadmium exposure, often resulting in slow-onset
proteinuria.
o Chronic
Gonzales & Cenina & Mamorno
• Acute effects of inhalation of fumes containing cadmium
include respiratory distress due to chemical pneumonitis
and edema and can cause death
• Breathing of cadmium vapors can also result in nasal
epithelial damage and lung damage similar to emphysema
• Cadmium exposure can affect the liver, bone, immune,
blood, and nervous systems
• EDTA can be used as a chelating agent in cadmium
poisoning
B. LABORATORY:
• Cadmium is usually quantified by GFAAS and ICPMS;
o ICP-AES is also used
• In blood, cadmium is found mostly (70%) in the RBCs
o Cadmium in blood reflects the average uptake during
the past few months and can be used for monitoring
purposes but does not accurately reflect a recent
exposure
• Urinary excretion is about 0.001% and 0.01% of the body
burden per 24 hours
o At low exposure, urine sample used.
CHROMIUM (Cr)
• Chromium (Cr), from the Greek word chroma (“color”),
makes rubies red and emeralds green
• 21st most abundant element in the earth’s crust
• used in the manufacturing of stainless steel
• Occupational exposure to chromium occurs in wood
treatment, stainless steel welding, chrome plating, the
leather tanning industry, and the use of lead chromate or
strontium chromate paints
• Chromium exists in two main valency states:
o trivalent – Cr(3+)
o hexavalent – Cr(6+)
NOTE
• Cr(6+) is better absorbed and much more toxic than Cr(3+)
• It requires carrier protein
o Both transferrin and albumin are involved in chromium
absorption and transport
▪ Transferrin binds the newly absorbed chromium
at site B,
▪ Albumin acts as an acceptor and transporter of
chromium if the transferrin sites are saturated
• Other plasma proteins, including β- (beta) and (gamma) γ-
globulins and lipoproteins, bind chromium.
A. HEALTH EFFECTS:
• Cr(3+) is an essential dietary element and plays a role in
maintaining normal metabolism of glucose, fat, and
cholesterol
• The estimated safe and adequate daily intake of chromium
for adults is in the range of 50-200 μg/d, although data are
insufficient to establish a recommended daily allowance
• Dietary chromium deficiency is relatively uncommon and
most cases occur in persons with specific clinical situations
such as total parenteral nutrition, diabetes, and
malnutrition.
• Chromium deficiency is characterized by glucose
intolerance, glycosuria, hypercholesterolemia, decreased
longevity, decreased sperm counts, and impaired fertility
• Enhances insulin action
• Cr(6+) compounds are powerful oxidizing agents and are
more toxic systemically than Cr(3+) compounds, given
similar amounts and solubilities
o At physiological pH, Cr(6+) forms CrO42- and readily
passes through cell membranes due to its similarity to
essential phosphate and sulfate oxyanions
o Intracellularly, Cr(6+) is reduced to reactive
intermediates, producing free radicals and oxidizing
deoxyribonucleic acid (DNA), both potentially inducing
cell death
o Severe dermatitis and skin ulcers can result from
contact with Cr(6+) salts
o Up to 20% of chromium workers develop contact
dermatitis.
▪ Allergic dermatitis with eczema has been
reported in printers, cement workers, metal
workers, painters, and leather tanners.
o Data suggest that a Cr(3+)–protein complex is
responsible for the allergic reaction
o When inhaled, Cr(6+) is a respiratory tract irritant,
resulting in airway irritation, airway obstruction, and
possibly lung cancer
• The target organ of inhaled chromium is the lung; the
kidneys, liver, skin, and immune system may also be
affected.
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 WEEK 13: TRACE ELEMENTS
• Low-dose, chronic chromium exposure typically results
only in transient renal effects
o Elevated urinary B2-microglobulin levels (an indicator
of renal tubular damage) have been found in chrome
platers, and higher levels have generally been
observed in younger persons exposed to higher Cr(6+)
concentrations
B. DEFICIENCY:
• Insulin resistance
• Impaired glucose tolerance
• Hyperlipidemia
• Glucose intolerance, glycosuria, hypercholesterolemia,
decreased longevity, decrease in sperm counts, and
impaired fertility
C. TOXICITY:
• Cr(6+) Powerful oxidizing agent
• CrO42+ At physiological pH
• It similarity to essential phosphate & sulfate anions
• Skin ulcer, renal & hepatic necrosis
• Severe dermatitis & skin ulcers
• Allergic dermatitis with eczema
• Cr (3+) - protein complex
• Airway irritant, airway obstruction, & possibly lung cancer
• Lung, kidneys, liver, skin, & immune system
• Transient renal effects
• Elevated urinary B 2 Microglobulin (an indicator of renal
tubular damage)
D. LABORATORY:
• GFAAS, NAA, or ICP-MS
• Plasma, serum, and urine do not indicate the total body
status of the individual, whereas urine levels may be useful
for metabolic studies
• In the setting of suspected failure of (metal on metal) MoM
hip implants that use a cobalt–chrome alloy femoral head,
serum is the preferred specimen type for both chromium
and cobalt analysis
COPPER (Cu)
• Relatively soft yet tough metal
• Excellent Electrical & heat conducting properties
• Copper is widely distributed in nature both in its elemental
form and in compounds
• Copper forms alloys with zinc (brass), tin (bronze), and
nickel (cupronickel, widely used in coins).
• Copper is an essential trace element found in four
oxidation states, Cu(0), Cu(1+), Cu(2+), and Cu(3+), with
Cu(2+) the most stable of all oxidation states
o Cuprous iron
• Cofactor of several metalloenzymes
• Critical for the reduction of iron in Heme synthesis
• Cellular respiration
• Collagen synthesis
NOTE
• The copper content in the normal human adult is 50-120
mg.
• Copper is distributed through the body with the highest
concentrations found in liver, brain, heart, and kidneys.
o Hepatic copper accounts for about 10% of the total
copper in the body
• Copper is also found in the cornea, spleen, intestine, and
lung
• The amount of copper absorbed from the intestine is 50-
80% of ingested copper
• The average daily intake is approximately 10 mg or more
of copper for adults.
• The exact mechanisms by which copper is absorbed and
transported by the intestine are unknown, but an active
transport mechanism at low concentrations and passive
diffusion at high concentrations have been proposed
o Copper is transported to the liver and bounds to
albumin, transcuprein, and low-molecular-weight
components in the portal system
o In the liver, copper is incorporated into ceruloplasmin
for distribution throughout the body
▪ Ceruloplasmin is an a2-globulin, and each
132,000 Da molecular weight molecule contains
six atoms of copper
o In a normal physiological state, 98% of copper
excretion is through the bile, with copper losses in the
urine and sweat comprising approximately 2% of
dietary intake.
• Menstrual losses of copper are minor
Gonzales & Cenina & Mamorno
A. HEALTH EFFECTS:
• Copper is a component of the different metalloenzymes in
the body such as:
o Ceruloplasmin, cytochrome C oxidase, superoxide
dismutase, tyrosinase, metallothionein, dopamine
hydroxylase, lysyl oxidase, clotting factor V and
unknown enzyme that cross links keratin in hair
B. DEFICIENCY:
• Seen in premature infants
• Seen in conditions involving impairment of copper
absorption which is seen in severe diffuse diseases of
small bowel, lymphosarcoma, & scleroderma
• Related to Malnutrition, malabsorption, chronic diarrhea,
hyperalimentation, & prolonged feeding with low copper,
total milk diets
• Signs of copper deficiency is
o (1) Neutropenia & hypochromic anemia in early
stages
o (2) Osteoporosis & various bone and joint
abnormalities, that reflect deficient copper-dependent
cross-linking of bone collagen and connective tissue
o (3) Decreased pigmentation of the skin and general
pallor
o (4) In latter stages, the patient may experience
neurologic abnormalities ( Hypotonia, apnea, and
psychomotor Retardation)
• Subclinical copper depletion contributes to an increased
risk of coronary heart disease
• Extreme copper deficiency is called “Menkes Disease” –
signs and symptoms usually appear at the age of 3
months after birth and usually they do not survive for long
and the maximum age that they could attain is age 5
o This invariably fatal, progressive brain, disease
characterized by peculiar hair, also known as the kinky
hair syndrome due to the presence of kinky or steely
hair, and retardation of growth.
o Clinical signs include progressive mental
deterioration, coarse feces, disturbance of muscle
tone, seizures, and episodes of severe hypothermia
C. HEALTH EFFECTS & TOXICITY:
• Copper toxicity is mostly associated with those living near
a copper producing facilities such as mining industries
where leakage of copper may happen
• Using water that passes through copper pipes or cooking
with copper lined vessels or exposure to algaecides,
herbicides, pyrotechnics, ceramic glazes, electrical wiring
or welding supplies
• Interferes with absorption of iron and zinc.
• Because of its redox potential, Copper is an irritant to
epithelia & mucus membranes and can cause Hepatic and
renal damage with hemolysis.
• Copper induced emesis has characteristic blue-green
color
• “Wilson’s Disease”
o Genetically determined copper accumulation disease
that usually presents between ages of 6 and 40 years
o Neurological disorders, liver dysfunction, and Kayser
Fleischer rings (green-brown discoloration) in the
cornea caused by copper deposition
o Early diagnosis of Wilson’s disease is important
because complications can be effectively prevented
and in some cases the disease can be halted with the
use of zinc acetate or chelation therapy
o Serum ceruloplasmin levels and the direct
measurement of free copper are key diagnostic steps
in the diagnosis of Wilson’s disease
INTERPRETATION OF COPPER TESTING RESULTS
SERUM URINE
COPPER COPPER
Nutritional deficiency ↓ ↓
Menkes syndrome ↓ ↑
Acute copper toxicity ↑ or ↑↑ ↑
Chronic copper toxicity ↑ ↑
Wilson’s disease N or ↓ ↑ or ↑↑
Smoking, inflammatory
↑ or ↑↑ N
conditions
Estrogen, pregnancy ↑ or ↑↑ N
N, normal; ↓, decreased; ↑, increased; ↑↑, Significantly
increased
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 WEEK 13: TRACE ELEMENTS
D. LABORATORY:
• Flame AAS, ICP-MS, ICP-AES and ASV
• Serum copper & urine copper are used to monitor for
nutritional adequacy and subacute management of copper
toxicity
• Direct measurement of free copper & Serum ceruloplasmin
in serum is used to screen for Wilson’s disease.
IRON (Fe)
• 4th most abundant element in the earth’s crust
• Most abundant transition metal
• Classified as a trace element in the body
• Oxygen transport
• Iron ions participates in redox chemistry in both ferrous
(Fe(2+)) and ferric (Fe(3+)) states allowing iron to fill
numerous biochemical roles as a carrier of other
biochemically active substances (e.g., oxygen) and as an
agent in redox and electron transfer reactions (e.g., via
various cytochromes).
NOTE
• Methods of extracting iron from ore have been known for
centuries
• The physical properties of iron alloys can be varied over
an enormous range by appropriate alloying and heat
treating methods, giving a range of strength, hardness,
toughness, corrosion resistance (in the form of stainless
steels), and magnetic properties and ability to take and
hold a sharp edge
• Iron’s high activity is a double- edged sword, and free iron
ions in the body also participate in destructive chemistry,
primarily in catalyzing the formation of toxic free radicals.
• As a result, very little free iron is normally found in the body.
ABSORPTION, TRANSPORT, AND EXCRETION
• Absorption of iron from the intestine is the primary means
of regulating the amount of iron within the body.
o Typically, only about 10% of the 1 g/d of dietary iron is
absorbed.
• To be absorbed by intestinal cells, iron must be in the
ferrous oxidation state and bound to protein. Because
Fe(3+) is the predominant form of iron in foods, it must first
be reduced to Fe(2+) by agents such as vitamin C or ferric
reductases present in the intestinal epithelium before it can
be absorbed.
• In the intestinal mucosal cell, Fe(2+) can be bound by
ferritin for storage and eliminated after sloughing off or be
exported to the basolateral side.
o From there, iron is oxidized to Fe(3+) and bound by
apotransferrin for transport throughout the body.
o The peptide hormone hepcidin regulates iron
absorption in the upper gastrointestinal tract by
modulating the export of iron from cells by ferroportin.
• After about 120 days in circulation, red cells are degraded
by the spleen, liver, and macrophages, which return Fe to
the circulation for reuse.
• Absorption and transport capacity can be increased in
conditions such as iron deficiency, anemia, or hypoxia.
• Iron is lost primarily by desquamation and red cell loss to
urine and feces.
o With each menstrual cycle, women lose
approximately 20-40 mg of iron.
• 2-2.5 g of iron is found in the hemoglobin mostly in RBC
and other red cell precursor.
o A moderate amount of iron (130 mg) in myoglobin,
the oxygen-carrying protein of muscle
o A small (8 mg) but extremely important pool is bound
in tissue to enzymes that require iron for full activity
▪ These include peroxidases, cytochromes, and
many of the Krebs cycle enzymes
• Iron is also stored as ferritin and hemosiderin, primarily in
the bone marrow, spleen, and liver
o Only 3-5 mg of iron is found in the blood circulation or
plasma and most of it are associated or bound to
transferrin, albumin and free hemoglobin
HEALTH EFFECTS
• Increased in serum Iron:
o a. Condition of increased erythrocyte destruction (
haemolytic anemia)
o b. Decreased blood formation (lead poisoning,
pyridoxine deficiency)
o c. Increased release of iron from the body of stores
(release of ferritin in acute hepatic cell necrosis)
o d. Defective iron storage (pernicious anemia)
o e. Increased rate of absorption (hemochromatosis and
transfusion siderosis)
Gonzales & Cenina & Mamorno
• Decreased in serum Iron:
o a. Generalized iron deficiency (lack of sufficient dietary
iron)
o b. Inadequate absorption of iron
o c. Chronic loss of iron as a result of bleeding or
nephrosis
o d. Impaired releases of iron from the reticuloendothelial
system (infection)
o e. Malignant
o f. Rheumatoid arthritis
• Increase in TIBC: Total iron binding capacity
o a. Iron deficiency
o b. Late pregnancy
o c. Oral contraceptives
o d. Viral Hepatitis
• Decreased in TIBC:
o a. Chronic infections
o b. Malignancy
o c. Iron poisoning
o d. Nephrosis
o e. Kwashiorkor
o f. Thalassemia
• Iron deficiency
o affects about 15% of the worldwide population.
o Those with a higher than average risk of iron
deficiency anemia include pregnant women, young
children, adolescents, and women of reproductive age
o Increased blood loss, decreased dietary iron intake, or
decreased release from ferritin may result in iron
deficiency
o Reduction in iron stores usually precedes both a
reduction in circulating iron and anemia, as
demonstrated by a decreased RBC count, mean
corpuscular hemoglobin concentration, and microcytic
RBCs
• Iron overload
o Hemochromatosis – abnormally high Fe absorption
▪ collectively referred to as hemochromatosis,
whether or not tissue damage is present
▪ HH is a single-gene homozygous recessive
disorder leading to abnormally high Fe
absorption, culminating in Fe overload
▪ HH causes tissue accumulation of iron, affects
liver function, and often leads to
hyperpigmentation of the skin
o Some conditions associated with severe
hemochromatosis include
▪ Diabetes mellitus, arthritis, cardiac arrhythmia,
cirrhosis, hypothyroidism, impotence, liver
cancer
o Treatment includes therapeutic phlebotomy or giving
them chelators such as deferoxamine
▪ Transferrin can be administered in the case of
atransferrinemia
• Secondary iron overload
o could be due to too much uptake of iron, diet,
medicine or transfusional iron intake or metabolic
dysfunction
o Hemosiderosis – Increased serum iron and high
TIBC and transferrin level In the absence of
o demonstrable tissue damage.
LABORATORY
• Disorders of iron metabolism are evaluated primarily by
packed cell volume, hemoglobin, red cell count and
indices, total iron and TIBC, percent saturation, transferrin,
and ferritin.
• TOTAL IRON CONTENT
o Fe(3+) bound to transferrin and not to the iron
circulating as free hemoglobin in serum
o Serum without anticoagulant or heparinized plasma
o Oxalate citrate and EDTA bind Fe ions and all are
unacceptable anticoagulants
o Early morning sampling preferred due to diurnal
variation in iron concentration
o Specimen with visible hemolysis should be avoided or
rejected
• TOTAL IRON BINDING CAPACITY (TIBC)
o Amount of iron that could be bound if transferrin and
other minor iron binding proteins present in the serum
or plasma sample were saturated
o Typically, only one-third of the iron-binding sites on
transferrin are saturated.
Page 4 of 8
 WEEK 13: TRACE ELEMENTS

• PERCENT SATURATION • Lead distributes to soft tissues, such as liver, kidneys, and
o The percent saturation, also called the transferrin brain, with the skeletal lead concentrations containing
saturation, is the ratio of serum iron to TIBC. greater than 90% of the body burden of lead.
o The Normal range for this is approximately 20% to 50% • Absorbed lead is excreted primarily in urine (76%) and
is the normal range but it varies with age and sex. feces (16%), and the remaining 8% is excreted in hair,
sweat, nails, and others
• TRANSFERIN
o Measured by immunochemical methods such as A. TOXICITY:
nephelometry. • The clinical presentation of lead toxicity is variable.
o Increased in iron deficiency • In children, obvious symptoms are usually seen at blood
o Decreased in Chronic infections & malignancy levels of 60 μg/dL or higher with 45 μg/dL as the typical
o Decreased in Iron overload & hemochromatosis threshold for acute, clinical intervention
• IQ declines are seen in children with blood lead levels
• FERRITIN (BLLs) of 10 ug/dL or higher
o Immunochemical methods
• Other central nervous system symptoms of lead toxicity in
o Decreased in Iron deficiency anemia
children may include clumsiness, gait abnormalities,
o Increased in Iron overload & hemochromatosis
headache, behavioral changes, seizures, and severe
o Often Increased in Chronic infections, malignancy, and
cognitive and behavioral problems
viral hepatitis
• Gastrointestinal symptoms include abdominal pain,
constipation, and colic. Other conditions may include
• A liver biopsy sample can be digested and analyzed for
acute nephropathy and anemia
iron by AAS and ICP-MS as a follow up to abnormal blood
• Other conditions may include acute nephropathy damage
tests consistent with an HH diagnosis
involving kidneys and anemia.
• Iron quantification in liver is not used for the evaluation of
acute iron toxicity.
NOTE
• Hepcidin testing has not yet been shown to be clinically
• The US Centers for Disease Control and Prevention
useful.
(CDC) estimates an incidence of more than 450,000 for
children with BLLs higher than 10 μg/dL. In adults, the
LABORATORY MARKERS OF IRON STATUS IN
following symptoms may be observed: peripheral
SEVERAL DISEASE STATES
SERU PERCENT
neuropathies, motor weakness, chronic renal insufficiency
TRANSFER FERRIT
CONDITION M
RIN IN
SATURATI TIBC and systolic hypertension, and anemia.
IRON ON
• Lead exposure primarily arises in two settings: childhood
Iron
↓ ↑ ↓ ↓ ↑ exposure, usually through paint chips, and adult
deficiency occupational exposure in the smelting, mining,
Iron overdose ↑ ↓ ↑ ↑ ↓ ammunitions, soldering, plumbing, ceramic glazing, and
Hemochromat Slightly construction industries. Other sources include lead-
↑ ↑ ↑ ↓
osis ↓ glazed ceramics and certain Asian herbal remedies. The
Variabl US government web sites contain extensive information
Malnutrition ↓ ↓ ↓ ↓
e on the health and environmental impacts of lead.
Chronic
↓ ↓ ↑ ↓ ↓
infection B. LABORATORY
Acute liver Varia
↑ Variable ↑ ↑ • ICP-MS is a preferred method of analysis, although ICP-
disease ble
AES and GFAAS are also used.
Chronic N or
↓ N or ↓ ↓ N or ↓ • The most common specimen type is whole venous blood,
anemia ↑
the result of which is commonly referred to as the BLL
N, normal; ↑, decreased; ↓, increased.
(Blood lead level)
o This is preferred over plasma and serum as
LEAD
circulating lead is predominantly associated with
• Soft, bluish white, highly malleable and ductile RBCs.
• Poor conductor of electricity & heat and resistant to • Elevated lead levels in capillary blood specimens should
corrosion be confirmed with a venous specimen to avoid the
potential contribution of external contamination.
NOTE
• Urine lead may be useful for detecting recent exposures
• Lead is widely distributed in the earth’s crust and the main to lead or to monitor chelation therapy
lead ores are galena, cerrusite, and anglesite.
• Other testing, such as plasma aminolevulinic acid, whole
• Lead is used in the production of storage batteries, blood zinc protoporphyrin, and free erythrocyte
ammunition, solder, and foils. protoporphyrins, may be useful for screening in
o Tetraethyl lead was once used extensively as an occupational exposures
additive in gasoline (petrol) for its ability to increase
• Noninvasive measurements of lead in bone may be
the fuel’s octane rating and is present in many paints
available radiographically. Removal of further lead
manufactured before 1970.
exposure and parental education are essential parts to
• The manufacture of lead-based household paints was the management for patients with elevated BLLs
banned in the United States in 1972 but is still used in
paints intended for non-domestic use. MERCURY (Hg)
• Toxic concentrations of lead can be found in areas • “Quicksilver”, is a heavy, silvery metal.
adjacent to homes painted with lead-based paints and
• Along with bromine, mercury is one of only two elements
around highways where it has accumulated from the past
that are liquid at room temperature and pressure.
use of leaded gasoline.
• Three (3) naturally occurring oxidation states of mercury
o In recent years, there have been massive recalls of
o Hg(0), Hg(1+), and Hg(2+).
toys and costume jewelry produced in China, due to
concerns over elevated lead content. Lead plays no • Organic mercury → refers to various forms of mercury
bound to a carbon atom, with mercury usually in the +2
known role in normal human physiology.
oxidation state.
ABSORPTION, TRANSPORT AND EXCRETION
NOTE
• Exposure to lead is primarily respiratory or gastrointestinal. • Mercury is a deadly liquid element that causes damage to
• Inhalation results in 30% to 40% of absorption efficiency. the nervous system.
Gut absorption depends on a variety of factors, including • Mercury is released to the atmosphere as a product of the
age and nutritional status, with enhanced gastrointestinal natural degassing of rock (30,000 tons/yr) and through
absorption occurring in children younger than 6 years of various human activities (20,000 tons/yr).
age. • Mercury is used in dental amalgams, electronic switches,
o The younger the age, the more efficient absorption germicides, fungicides, and fluorescent light bulbs.
which is not good o Very small amount of mercury coming from dental
• Certain substances, such as iron, calcium, magnesium, amalgams → 3 pieces is considered to be acceptable;
alcohol, and fat, may weaken lead absorption while low doesn’t have too much impact in our health
dietary zinc, ascorbic acid, and citric acid can enhance the • Mercury is used before as a typical composition of
absorption of lead. medication; considered before having an anti-bacterial
• About 99% of absorbed lead is taken up by erythrocytes effect.
where it interferes with heme synthesis. o

Gonzales & Cenina & Mamorno Page 5 of 8

 WEEK 13: TRACE ELEMENTS
o The use of mercury in medicine has greatly declined in
all respects; however, mercury compounds are found
in some over-the-counter drugs, including topical
antiseptics, stimulant laxatives, diaper-rash ointment,
eye drops, and nasal sprays.
o Mercury is widely used in the production of eye
cosmetics, especially mascara.
• Mercury thermometer is utilized before the digital
thermometer
o Sphygmomanometer (for blood pressure) is also
containing mercury (old version);
o Primarily the reason why we use digital thermometer
nowadays is because of the law that banned or stop
the utilization of mercury because of its toxic effects.
Since it depends especially on the form that is ingest or
expose to an individual.
A. HEALTH EFFECTS & TOXICITY
• Cause or trigger autism in children
• Mercury has no known function in normal human
physiology. Toxicities have been observed following
inhalation, ingestion, and dermal absorption of mercury
compounds.
• Mercurial salts were historically used as diuretics, topical
disinfectants, and laxatives before mercury toxicity was
well understood.
• Since the 1930s, some vaccines contained the
preservative thimerosal, a mercury-containing compound
metabolized into ethylmercury
• Organic mercury and elemental mercury vapor are toxic to
both the central and peripheral nervous systems.
• Mercury attacks the central nervous system well before a
victim shows symptoms
• Professor Karen Wetterhahn, the founding director of
Dartmouth College’s Toxic Metals Research Program and
an expert in the mechanisms of metal toxicity, died in 1997,
at the age of 48, because of a tragic laboratory accident
involving the use of dimethylmercury.
• Mercury intoxication can manifest in many signs and
symptoms that affect several organ systems, including:
o Headache, tremor, impaired coordination,
abdominalcramps, diarrhea, dermatitis,
polyneuropathy, proteinuria, and hepatic dysfunction
• The toxicity of mercury is primarily through reaction with
protein sulfhydryl groups (MSH), resulting in dysfunction
and inactivation.
• Liquid elemental mercury is poorly absorbed and
relatively nontoxic but elemental mercury vapor is highly
absorbed and is highly toxic.
• Inorganic, ionized forms of mercury are toxic. Further
bioconversion to an alkyl mercury, such as MeHg, yields
a very toxic species of mercury that is highly selective for
lipid-rich mediums such as the brain
NOTE
• Different routes of exposure:
o 1. Inhalation, primarily as elemental mercury vapor
but occasionally as dimethyl mercury
▪ Inhalation → Elemental mercury vapor
✔ Elemental mercury readily vaporizes, and
its inhalation can produce harmful effects
on the nervous, digestive, and immune
systems and the lungs and kidneys.
▪ Inhalation → Dimethyl mercury
o 2. Ingestion of HgCl2 and mercury-containing foods
such as predatory fish species;
▪ Mercury chloride or mercury containing food /
Fish species that has mercury contents →
legitimate shark spins, fish na walang kalislis
(such as tulingan) or tuna (depends on the
content of mercury or the omega-3 of that fish.
The higher the content of omega-3 the less the
absorption therefore lowers the amount of
possible presence of mercury in the fish)
o 3. Cutaneous absorption of methyl mercury (MeHg) →
through the skin and even through latex gloves
o 4. Injection of relatively inert liquid mercury and
mercury-containing tattoo pigments
o 5. Dental amalgams
NOTE
• Inhaled mercury vapor is retained in the lungs to about
80%, whereas liquid metallic mercury passes through the
gastrointestinal tract (GIT) largely unabsorbed
• Mercury enters the food chain primarily by volcanic
activity and manmade sources such as coal combustion,
mining and smelting.
Gonzales & Cenina & Mamorno
o Potent or common source in the Philippines → Mining
company who were mining golds from several
provinces, or small mining industries that uses
mercury as an amalgams to bind or para magdikit dikit
yung gold
o Dead bodies of water or river that has been
contaminated because of mining
• Most of the dietary intake comes from consumption of
meat and fish products, with estimates of dietary intake
varying based upon geographical location and dietary
sources.
• Organs that are affected due to mercury exposure:
o The kidney is the major storage organ after elemental
or inorganic mercury exposure.as well as methyl
mercury
o MeHg is efficiently absorbed from the gastrointestinal
tract, and distribution to tissues, including the brain,
appears complete in 48 hours.
▪ Movement of MeHg across the blood–brain
barrier appears to be dependent on coupling
with the amino acid cysteine.
• There is relatively little bioaccumulation of inorganic and
elemental mercury. Half-lives vary according to the route
of exposure and form of mercury, from 5 days in blood for
phenylmercury to 90 days in urine for chronic exposure to
inorganic mercury
o Normally, the highest accumulation of mercury is in
the kidney, liver, spleen, and brain. Mercury can
accumulate in pituitary and thyroid glands, the
pancreas, and the reproductive organs.
▪ The bulk of mercury accumulated in the body
is eliminated in approximately 60 days;
however, organic forms of mercury can
accumulate in brain and may take up to
several years to be eliminated.
o Fecal and urinary excretions are the main elimination
routes for inorganic and organic mercury.
o A special form of elimination is the transfer of mercury
from the fetus through the placenta.
B. LABORATORY
• Analytical methods include:
o ICP-MS
o Cold vapor AAS
• Mercury is usually determined as total mercury levels in
blood and urine without regard to chemical form.
MANGANESE (Mn)
• 12th most abundant element in the earth’s crust
• Found in over 250 minerals
o of which 15 have commercial importance
• Constituent of metalloenzymes and as an enzyme
activator
o It acts as an activators (metalloenzymes)
NOTE
• We used manganese for industrial purposes such as for
steel production, production of batteries, and fertilizers and
so on and so forth.
o Nearly all the elemental manganese is used in the
production of the alloy ferromanganese widely used in
steel production.
o Other uses of elemental manganese include a
scavenger role in copper and aluminum alloys and in a
production of dry cell batteries.
o Various manganese compounds are widely used in
fertilizers, animal feeds, pharmaceutical products,
dyes, paint dryers, catalysts, and wood preservatives
and in production of glass and ceramics.
• Majority of manganese are obtained through ingestion
o Roughly, 2-15% of dietary manganese is absorbed in
the small intestine
o Dietary factors that affect manganese absorption
include iron, calcium, phosphates, and fiber.
• Manganese absorption is age dependent, with infants
retaining higher levels of manganese than adults do.
• Manganese is a normal component in tissue with the
highest levels found in fat and bone.
• Though accumulation of manganese in the healthy
population has not been observed, chronic liver disease or
other types of liver dysfunction can reduce manganese
elimination and promote accumulation in various regions
of the brain.
• Manganese elimination occurs predominately through the
bile.
Page 6 of 8
 WEEK 13: TRACE ELEMENTS
A. HEALTH EFFECTS
• Manganese is biochemically essential as a constituent of
metalloenzymes and as an enzyme activator.
• Manganese-containing enzymes include:
o Arginase, pyruvate carboxylase, and manganese
superoxide dismutase in the mitochondria.
• Manganese-activated enzymes include:
o Hydrolases, kinases, decarboxylases, and
transferases.
• Many of these activations are not specific to manganese
and other metal ions (magnesium, iron, or copper) can
replace manganese as an activator and mask the effects
of manganese deficiency.
B. DEFICIENCY
• Blood clotting defects, hypocholesterolemia, dermatitis,
and elevated serum calcium, phosphorus, and alkaline
phosphatase activity have been observed in some
subjects who underwent experimental manganese
depletion.
• Low levels of manganese have been associated with
Epilepsy, hip abnormalities, joint disease, congenital
malformation, heart and bone problems, and stunted
growth in children
C. TOXICITY
• Manganese toxicity causes Nausea, vomiting, headache,
disorientation, memory loss, anxiety, and compulsive
laughing or crying.
• Chronic manganese toxicity resembles Parkinson’s
disease with akinesia, rigidity, tremors, mask-like faces.
• A clinical condition named locura manganica
(manganese madness) was described in Chilean
manganese miners with acute manganese aerosol
intoxication.
o Manganese toxicity - umiiyak tapos biglang tumatawa
(krazzzy)
o Too much manganese inhaled due to mining industry.
D. LABORATORY
• Manganese is measured by ICP-MS and GFAAS
• Urine manganese is used in conjunction with serum
manganese to evaluate possible toxicity or deficiency.
MOLYBDENUM (Mo)
• Hard, silvery white metal
• Occurring naturally as Molybdenite, wulfenite, & powellite
NOTE
• Most molybdenum is used for the production of alloys, as
well as catalysts, corrosion inhibitors, flame retardants,
smoke depressants, lubricants, and molybdenum blue
pigments.
• Molybdenum is an essential trace element with the
importance of molybdenum-containing organic
compounds in biological systems identified over 80 years
ago.
• Dietary intake
o Between 25% and 80% of ingested molybdenum is
absorbed predominately in the stomach and small
intestine with the majority of absorbed molybdenum
retained in the liver, skeleton, and kidney.
• In blood, molybdenum is extensively bound to α2-
macroglobulin and RBC membranes.
• Molybdenum can cross the placental barrier, and
increased intake of molybdenum in the diet of the mother
can increase its level in the liver of the neonate.
A. HEALTH EFFECTS
• Molybdenum is vital to human health through its inclusion
in at least three enzymes:
o Xanthine oxidase, aldehyde oxidase, and sulfite
oxidase
• The active site of these enzymes binds molybdenum in the
form of a cofactor “Molybdopterin”
• Dietary molybdenum deficiency is rare with a single case
reported because of total parenteral nutrition in a man with
Crohn’s disease.
• Molybdenum cofactor deficiency is a recessively inherited
error of metabolism due to a lack of functional
molybdopterin.
o The symptoms include seizures, anterior lens
dislocation, decreased brain weight, and usually death
prior to 1 year of age.
Gonzales & Cenina & Mamorno
• Molybdenum toxicity is rarely reported, as there are few
known cases of human exposure to excess molybdenum.
• High dietary and occupational exposures to molybdenum
have been linked to elevated uric acid in blood and an
increased incidence of gout.
• Molybdenum is rapidly eliminated in both urine and bile,
with urine excretion predominating when intake is high.
B. LABORATORY
• Molybdenum levels are measured by ICP-MS and
GFAAS
• Blood levels are less than 60 μg/L
SELENIUM (Se)
• Naturally occurring metalloid with many chemical and
physical properties similar to those of sulfur.
• Similar to sulfur (chemical & physical)
• Essential trace elements
• Major constituent of 40 minerals & minor constituent of 37
others
NOTE
• Most processed selenium is used in the electronics
industry; however, other uses include nutritional
supplements, pigments, pesticides, rubber production,
anti-dandruff shampoos, and fungicides.
A. HEALTH EFFECTS
• Glutathione peroxidase (in the form of selenocysteine) is
part of the cellular antioxidant defense system against free
radicals and selenium is also involved in the metabolism of
thyroid hormones61 (e.g., deiodinase enzymes and
thioredoxin reductase).
NOTE
• Selenium is well absorbed from the gastrointestinal tract
(~50%).
• Selenium exposure occurs primarily from food but can be
found in drinking water, usually in the form of inorganic
sodium selenate or sodium selenite.
• Selenium homeostasis is largely achieved by excretion via
urine and feces.
• Other routes of elimination include sweat and, at very high
intakes, exhalation of volatile forms of selenium.
• In the 1930s, selenium was considered a toxic element; in
the 1940s, a carcinogen; in the 1950s, it was declared as
an essential element; and since the 1960s and especially
the 1970s, it has been viewed as an anticarcinogen.
B. DEFICIENCY
• Selenium deficiency has been associated with:
o Cardiomyopathy, skeletal muscle weakness, and
osteoarthritis
• A significant negative correlation was observed between
selenium intakes and the rate of cancer of the large
intestine, rectum, prostate, breast, ovary, and lungs and
leukemia.
• “Keshan disease” → an endemic cardiomyopathy that
affects mostly children and women in childbearing age in
certain areas in China, has been associated with selenium
deficiency.
o Symptoms include dizziness, malaise, loss of appetite,
nausea, chills, abnormal electrocardiograms,
cardiogenic shock, cardiac enlargements, and
congestive heart failure.
▪ Readily elevated through selenium
supplementation has been shown to effectively
control Keshan disease.
• “Kashin-beck disease” → an endemic osteoarthritis that
occurs during adolescent and preadolescent years, is
another disease linked to low selenium status in northern
China, North Korea, and eastern Siberia.
C. TOXICITY
• Acute oral exposure to extremely high levels of selenium
may produce gastrointestinal symptoms such as nausea,
vomiting, and diarrhea
o and cardiovascular symptoms such as Tachycardia
• Chronic exposure to very high levels can cause dermal
effects, including:
o Diseased Nails and skin and hair loss, as well as
neurologic problems such as unsteady gait or paralysis
• The EPA has determined that one specific form of
selenium, selenium sulfide, is a probable human
carcinogen.
Page 7 of 8
 WEEK 13: TRACE ELEMENTS

o Selenium sulfide is a very different chemical from the B. DEFICIENCY

organic and inorganic selenium compounds found in
foods and in the environment.
• In Hubei Province (China) during 1961 through 1964,
almost half of the population of many villages died from
chronic selenosis.
o The most common signs of selenium poisoning were
loss of hair and nails, skin lesions, tooth decay, and
abnormalities of the nervous system.
NOTE
• In the 1930s, selenium was considered a toxic element; in
the 1940s, a carcinogen; in the 1950s, it was declared as
an essential element; and since the 1960s and especially
the 1970s, it has been viewed as an anticarcinogen
• Glutathione peroxidase (in the form of selenocysteine) is
part of the cellular antioxidant defense system against
free radicals and selenium is also involved in the
metabolism of thyroid hormones (e.g., deiodinase
enzymes and thioredoxin reductase).
D. LABORATORY
• Selenium is most often determined by ICP-MS or GFAAS.
• The determination of urinary and blood selenium is an
useful measure of selenium status.
ZINC (Zn)
• Bluish-white lustrous metal that is stable in dry air and
becomes cover with a white coating when exposed to
moisture.
• Zinc is used in a production of alloys, especially brass (with
copper), in galvanizing steel, in die casting, in paints, in
skin lotion as treatment for Wilson’s disease, and in many
over-the-counter medications.
o Treatment for “Wilson’s disease”
• Zinc is an essential trace element and deficiency is
common throughout life, especially in individuals that do
not ingest meat.
• The body content in a normal individual varies substantially
with age and is predominantly distributed in the muscle
(60%) and skeleton (30%).
• The remaining 10% is distributed in various other tissues
with highest concentrations found in the eyes, prostate,
and hair.
• Zinc absorption mainly occurs in the small intestine and
especially in the jejunum.
• Factors increasing zinc absorption include the presence of
animal proteins and amino acids in a meal, intake of
calcium, and unsaturated fatty acids.
• Conversely, factors decreasing zinc absorption include the
intake of iron, taking zinc on empty stomach, presence of
copper at high levels, and age.
• In blood, the absorbed zinc is distributed between RBCs
(80%), plasma (17%), and white blood cells (3%). In
normal dietary circumstances, about 90% of zinc is
excreted in feces/stool.
• Zinc deficiency causes: Growth retardation, slows skeletal
maturation, causes testicular atrophy, and reduces taste
perception.
• Old age, pregnancy, lactation, and alcoholism are also
associated with poor zinc nutrition.
• Infants with acrodermatitis enteropathica (zinc
malabsorption)
o First develop a characteristic facial and diaper rash
o If untreated, symptoms progress and include:
▪ Growth retardation, diarrhea, impaired T-cell
immunity, insufficient wound healing, infections,
delayed testicular development in adolescence,
and early death
• Zn deficiency in adolescents is manifested by:
o Slow growth or weight loss, altered taste, delayed
puberty, dwarfism, impaired dark adaptation, alopecia,
emotional instability and tremors.
• In severe cases, lymphopenia and death can result from
an overwhelming infection.
C. TOXICITY
• Zinc is relatively nontoxic.
• Nevertheless, high doses (1 g) or repetitive doses of 100
mg/d for several months may lead to gastrointestinal tract
symptoms, decrease in heme synthesis due to an
induced copper deficiency, and hyperglycemia
• Exposure to ZnO fumes and dust may cause “zinc fume
fever,” with symptoms including chemically induced
pneumonia, severe pulmonary inflammation, fever,
hyperpnea, coughing, pains in legs and chest, and
vomiting
D. LABORATORY
• Zinc is measured by: FAAS, ICP-AES, ICP-MS
• Low urine zinc levels in the presence of low serum zinc
levels usually confirm zinc deficiency.
NOTE
• Low serum zinc in an apparently healthy (nonstressed and
nonseptic) patient who has normal serum albumin levels
can be used as evidence of zinc deficiency, especially if
urine zinc levels are also low.
• Normal serum zinc cannot be interpreted as evidence of
normal zinc stores.
• Zinc concentration in RBCs is approximately 10 times that
in serum.
• Copper status should be monitored in patients undergoing
long-term zinc therapy.

A. HEALTH EFFECTS
• Oxidoreductases, transferases, hydrolases, leases,
isomerases, and lipases.
• Synthesis and metabolism of DNA & RNA
• Synthesis and metabolism of proteins
• Metabolism of glucose and cholesterol, membrane
structure maintenance, insulin function, and growth factor
affects

NOTE
• Zinc is second only to iron in importance as an essential
trace element.
• The main biochemical role of zinc is seen in its influence
on the activity of more than 300 enzymes in classes such
as oxidoreductases, transferases, hydrolases, leases,
isomerases, and lipases.
• As a result of the importance of zinc for the structure,
regulation, and catalytic action of various enzymes, zinc is
indirectly involved in the synthesis and metabolism of DNA
and RNA, the synthesis and metabolism of proteins, the
metabolism of glucose and cholesterol, membrane
structure maintenance, insulin function, and growth factor
affects.
• Chronic oral zinc supplementation interferes with copper
absorption and may cause copper deficiency forming the
basis for using zinc to treat Wilson’s disease.

Gonzales & Cenina & Mamorno Page 8 of 8