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Trace elements
Definition
• Inorganic micronutrients present at very low
concentrations in body fluids and tissue.
– Present at
• (μg/dL) in body fluids
• (mg/kg) in tissue
• Amounts required
– Micrograms per day
– Dietary requirements
• mg/day
Classification of Trace Mineral Elements
The biological function
• Essential
– The signs and symptoms induced by a deficient
diet are uniquely reversed by an adequate supply
of the particular trace element
– Clinical examples
• Iron-deficiency anemia
• Goiter (iodine)
Trace elements
• When insufficient, deficiency symptoms may
arise, and if present in excess they may be
toxic
• Depending upon
– The element in question,
– The nature of the chemical species present in the
diet.
Trace elements
• In the form of metalloenzymes
– Intermediary metabolism
• Transport and safe storage
– Examples
• Metallothionein (Cu, Zn), transferrin, ferritin and
hemosiderin (Fe),and ceruloplasmin (Cu).
• Absorption, transport, uptake and storage,
control of excretion.
Trace elements
• Excretory route
– Intestinal tract in bile and other intestinal fluids
• By regulation of initial absorption and by resecretion
– In feces
– (Zn, Cu)
– Urine
• Halides
• Other routes
– Hair and/or nails, skin cell desquamation, and in sweat
• Minor
Trace elements
• Trace element deficiency disease
– Poor dietary supply
– Malabsorption
• Antagonistic effects
• Blockage of uptake by substances
• Increased excretory losses
– Disease, injury, and infection
• Inborn errors
– Defects in the metabolism of trace elements
• Hemochromatosis
• Wilson's disease and Menkes' syndrome)
Trace elements
• Acrodermatitis enteropathica
• Molybdenum cofactor disease
INTERACTIONS
•
•
•
•
•
Between different essential trace elements
With the other essential major minerals
Affecting the intestinal bioavailability
Synergistic and antagonistic
Example,
– Zinc ions block copper absorption
– Molybdate ion can form insoluble coppermolybdate
– Between molybdenum and tungsten.
INTERACTIONS
• Organic phosphate (phytic acid) in limiting zinc
absorption
• Synergistic interactions
– Selenium and iodine
• Selenoproteins
– Deiodinases
– Glutathione peroxidase
• Zinc and vitamin A
– Zinc depletion limits the bioavailability of vitamin
A.
• Deficiencies
– Interference from other dietary ingestants
– Lack of a protein needed to absorb or metabolize
the element.
– Total parenteral nutrition
• The roles of the trace mineral elements
– Structural, signal transduction
– as enzyme co factors
• Electron and oxygen transport
– Maintenance of macromolecule conformation
• Genetic defects in trace element metabolism
–
–
–
–
Menkes’
Congenital atransferrinemia
Acrodermatitis enteropathica
Xanthine and sulfite oxidase
• Trace element analysis
– Atomic absorption spectrometry (AAS)
• Assessment of trace element
– Activity of a trace element-dependent enzyme
– Concentration in accessible tissues
Laboratory assessment
• Indirect determination
– Metalloenzymes and protein species
• Iodine
• Assay of the thyroid hormones and of their control and
feedback systems
• Cobalt
– Cobalamin (Immunoassay)
• Direct methods
– Analytical difficulties
– Sample contamination
Laboratory assessment
• Carrier proteins
• Transferrin (Fe), albumin (Zn), ceruloplasmin (Cu), and
selenoprotein P (Se)
• Can give useful additional information.
– Analytical consideration
• Prolonged storage of samples
– Storage at 4 °C to 10 °C with a rapid turnaround analytical time is
good practice.
– Repeated freezing and thawing
» Precipitation of proteins and nonhomogeneous samples.
Preanalytical Factors
• Effect of disease
– Hepatic synthesis of some plasma proteins
• acute phase proteins
– Proteins increase
» Metals increase
– Inflammatory response
• Increased permeability
– Metal kinetics and distribution
Individual trace elements
Chromium
• Function/enzyme component
– Potentiates insulin action
– Glucose and lipid metabolism
– Cr(lll) low toxicity
– Poorly absorbed
– Component of glucose tolerance factor
Chromium
• Effects of deficiency
– No method to determine deficiency in humans
– Impaired glucose tolerance in type 2 diabetes
– Insulin resistance
– Hyperglycemia
– Peripheral neuropathy
– Hyperlipidemia
Chromium
• Effects of toxicity
– Cr(VI)toxic, oxidative damage, skin ulcers,
– Contact dermatitis, asthma, renal and hepatic
necrosis, lung cancer
Cobalt
• Function
– Hemoglobin synthesis
– Component of vitamin B12
• Effects of deficiency
– Cobalt deficiency, as such, not in humans
– Symptoms due to lack of vitamin B12
– Anemia , anorexia, growth depression
Cobalt
• Effects of toxicity
– Cardiomyopathy, heart failure, goiter,
– hypothyroidism; warm sensation, vomiting,
diarrhea
Copper
• Function
– Cellular respiration, neurotransmitter regulator,
– Oxidation reaction, electron transport, collagen
– Synthesis, development of vascular and skeletal
Structures and CNS
– Antioxidant Component of CuZnSOD,
metallothionein,
– Cytochrome c, tyrosinase, dopamine βhydroxylase, Iysyl oxidase
Effects of deficiency
• Menkes' kinky hair syndrome: X-linked;
congenital failure of Cu absorption
• Abnormal collagen crosslinking, muscle
weakness, iron-refractory hypochromic anemia,
leukopenia, neurological defects,
hypopigmentation
• In prematurity: bone fractures, skeletal defects
– Occurs in malnourished children and premature
infants not supplemented
Effects of toxicity
• Relatively nontoxic
• Wilson's disease: autosomal recessive; failure
to excrete Cu in bile
• Excess Cu in liver, kidneys, brain, eyes; hepatic
necrosis, hypertension,Kayser-Fleischer rings
in eyes
• Cu interferes with absorption of iron and zinc
Fluorine
• Function
– Prevents tooth decay
• Effects of deficiency
– Increased dental caries
• Effects of toxicity
– Mottled enamel, fluorosis
Iodine
• Function
– Component of thyroid hormone
• Effects of deficiency
– Goiter, hypothyroidism, cretinism in infants,
myxedema in adults
• Effects of toxicity
– Goiter, thyrotoxicosis
Iron
• Function/enzyme component
– Oxygen transport, respiration, amino acids and
– free radical metabolism, lipids, oxidative
– Phosphorylation, Component of hemoglobin,
metalloenzymes, vitamin A
Effects of deficiency
•
•
•
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Hypochromic microcytic anemia,
glossitis, angular stomatitis, cheilosis,
Blood loss or inadequate iron intake;
iron deficiency anemia: < 7 g/100 mL blood
Effects of toxicity
• Hemochromatosis: genetic, primary,
autosomal recessive acquired, secondary, iron
overload iron deposition in liver, pancreas,
heart and skin
Manganese
• Function/enzyme component
– Bone and connective tissue
– Component of metalloenzymes: hydrolases,
– Oxidoreductases, and lipases, pyruvate caboxylase
– Superoxide dismutase, and arginase
Effects of deficiency
• Not well-defined in humans
• Skeletal and cartilage defects
• Effects of toxicity
– Least toxic of trace elements
– Psychiatric disorders: memory, speech,
– hallucinations; syndrome resembles Parkinson's
– and WiIson's diseases
Molybdenum
• Function
– DNA metabolism, essential for uric acid
Production
– Component of sulfite and xanthine oxidase
• Effects of deficiency
– Naturally occurring deficiency not known;
– Growth depression, hypercuprinemia, defective
keratin formation, goiter, cretinism
Effects of toxicity
• Anemia, goiter, thyrotoxicosis
• Hypouricemia,hyperoxypurinemia
Selenium
• Function
– Protects against oxidative damage of lipid,
– gene expression, thyroxin deiodinase
– Component of glutathione peroxidase
Effects of deficiency
• Cardiomegaly, heart failure, cataracts,
• Osteoarthritis in children, myopathy,
• discolored/thickened nails, impaired growth
Effects of toxicity
• Hair and nail loss, selenosis, tooth decay,
• neuropathy, liver failure, garlic odor on breath
Zinc
• Function
– Protein synthesis, zinc finger proteins - gene
– expression, immunity, needed for normal skin,
– bones and hair Component of metallothionein, 300 enzymes
Effects of deficiency
• Acrodermatitis enteropathica; causes
– Cardiomyopathy in children
• In children, low height, hypogeusia,
• growth retardation, infertility, immune
• deficits, delayed wound healing, glossitis,
seborrheic-like dermatitis, osteoporosis
Effects of toxicity
• Relatively nontoxic, nausea, vomiting
• GI-irritation, causes copper deficiency
Properties of Essential Trace Mineral
Elements