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 copper-

molybdate– 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 β-

hydroxylase, 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

• 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