TRACE MINERALS�(Cu,Zn, Li)

MINERALS

• Minerals are essential for the normal growth and maintenance of the body
• Requirement: >100 mg/day (Major elements )

< 100 mg/day (Trace elements )

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• Major elements:- Calcium, magnesium, phosphorus, sodium, potassium, chloride, sulfur
• Trace elements:- Iron, iodine, copper, manganese, zinc, molybdenum, selenium, fluoride

Trace Minerals

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January 6, 2017

COPPER

• Total body copper:- 100 mg.
• Seen in muscles, liver, bone marrow, brain, kidney, heart and in hair
• Copper containing enzymes: Ceruloplasmin, cytochrome oxidase, cytochrome c, tyrosinase, lysyl oxidase, ALA synthase, monoamine oxidase, superoxide dismutase and phenol oxidase.
• Nonenzymatic proteins:- hepatocuprein in liver (storage form), cuprothionine in liver, cerebrocuprein in brain, hemocuprein in RBC and erythrocuprein in bone marrow
• Hemocyanin is the oxygen carrying blue pigment seen in crustacea

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January 6, 2017

• Requirement : Adult: 1.5-3.0 mg/day
• Sources: cereals, meat, liver, nuts and green leafy vegetables.
• Milk is very poor in copper content.
• Only about 10% of dietary copper is absorbed
• Excretion is mainly through bile
• Urine does not contain copper in normal circumstances

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January 6, 2017

• Whole blood contains about 100 µg/dl of copper.
• Out of this, 95% is in RBC as colorless erythrocuprein.
• In plasma Ceruloplasmin is an important copper containing protein
• 25-50 mg/dl (blue-colored glycoprotein)
• Also k/a Serum ferroxidase
• Oxidation of Fe⁺⁺→ Fe⁺⁺⁺, which is incorporated into transferrin
• About 10% of copper in plasma is loosely bound with Albumin, which constitutes the transport form of copper

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January 6, 2017

• Functions:-
• Iron absorption and incorporation of iron into hemoglobin
• For tyrosinase activity
• It is a co-factor for vitamin C requiring hydroxylations.

(Dopamine β hydroxylase, peptidylglycine hydroxylase)

• Increases HDL and so protects the heart.

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January 6, 2017

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January 6, 2017

• Abnormal Metabolism of Copper:-
• Wilson's Disease
• Aceruloplasminemia
• Copper Deficiency Anemia
• Cardiovascular Diseases
• Menke's Kinky Hair Syndrome
• Melanin

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January 6, 2017

• Wilson's Disease:-
• Ceruloplasmin level in blood: drastically reduced
• Incidence is 1 in 50,000
• The basic defect is in a gene encoding a copper binding ATPase in cells (ATP7B gene in liver cells).
• This is required for normal excretion of copper from liver cells;
• In its absence, copper is accumulated in cells, leading to copper deposits in liver and brain
• Treatment: Administration of penicillamine

Zinc decreases copper absorption

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January 6, 2017

• Aceruloplasminemia:
• Levels of ceruloplasmin (ferroxidase) activity are congenitally low
• So, iron is not utilized properly
• Iron accumulates in brain, liver and pancreatic islet cells.
• Neurological symptoms are seen.
• Copper Deficiency Anemia:-
• ALA synthase
• Copper helps the uptake of iron by normoblasts
• Microcytic hypochromic anemia

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Trace Minerals

10

January 6, 2017

• Cardiovascular Diseases:-
• lysyl oxidase
• It oxidizes four lysine residues together to form desmosine which makes cross linkages in elastin.
• In deficiency elastin becomes abnormal, leading to weakening of walls of major blood vessels
• Aneurysm and fatal rupture of the wall of aorta
• Fibrosis of myocardium leading to cardiac failure.

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January 6, 2017

• Menke's Kinky Hair Syndrome:-
• X-linked defect
• Dietary copper is absorbed from GI tract; but cannot be transported to blood due to absence of an intracellular copper binding ATPase (mutation in ATP7A gene)
• Copper is not mobilized from intestinal cells as well as in other tissue cells
• The copper that has entered into the cell is not able to get out of the cells, and so it accumulates.
• Copper is not available for metabolism, resulting in defective cross-linking of connective tissue.
• Vascular and connective tissues are affected.
• Child dies usually in infancy

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January 6, 2017

• Melanin:
• Tyrosinase which is necessary for melanin formation
• Hypo pigmentation and in extreme cases, grey color of hair.
• Alternate white patches on hair ; sometimes called flag type of hair growth
• Low levels can cause brain dysfunction, especially of the cerebellum, leading to ataxia

Trace Minerals

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January 6, 2017

• Copper Toxicity:
• Oxidize proteins and lipids; it can enhance production of free radicals
• Diarrhea and blue-green discoloration of saliva
• Hemolysis, hemoglobinuria, proteinuria and renal failure.
• Excess intake of copper will induce the synthesis of metallothionein (MT), found in liver, kidney and intestine.
• MT has a high content of cysteine and binds copper, zinc, cadmium and mercury.
• MT binds these metals, so as to make them nontoxic.
• Alzheimer’s disease.

Trace Minerals

14

January 6, 2017

IODINE

• Requirement : 150-200 µg/day
• Sources: drinking water, fish, cereals, vegetables and iodinated salt.
• Total body contains : 25-30 mg of iodine
• All cells do contain iodine; but 80% of the total is stored in the thyroid gland.
• In blood is 5-10 µg/dl
• Upper regions of mountains generally contain less iodine: Goiterous belts (Himalaya region)
• Goitrogens: seen in cassava, maize, millet, bamboo, sweet potatoes and beans.

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January 6, 2017

• Cabbage and tapioca contain thiocyanate, which inhibits iodine uptake by thyroid
• Mustard seed contains thiourea, which inhibits iodination of thyroglobulin
• The only biological role of iodine is in formation of thyroid hormones, thyroxine (T₄) and tri-iodo thyronine (T₃).

Trace Minerals

16

January 6, 2017

ZINC

• Total zinc content of body is about 2 gm,
• 60% is in skeletal muscles and 30% in bones
• Highest concentration: In hippocampus area of brain and prostatic secretion.
• Dietary sources:- grains, beans, nuts, cheese, meat and shellfish.
• Requirement:- For adults is 10 mg/day
• Copper, calcium, cadmium, iron and phytate will interfere with the absorption of zinc.
• Zinc and copper will competitively inhibit each other's absorption.

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January 6, 2017

• In liver, zinc is stored in combination with a specific protein, metallothionein.
• Excreted through pancreatic juice and to a lesser extent through sweat.
• Zn containing enzymes: carboxypeptidase, carbonic anhydrase, alkaline phosphatase, lactate dehydrogenase, alcohol dehydrogenase and glutamate dehydrogenase
• RNA polymerase contains zinc and so it is required for protein biosynthesis.
• Extracellular superoxide dismutase is zinc dependent and so, zinc has antioxidant activity.

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January 6, 2017

• Insulin when stored in the beta cells of pancreas contains zinc, which stabilizes the hormone molecule
• Protamine-zinc-insulinate (PZI) also contains zinc
• Zinc containing protein, Gusten, in saliva is important for taste sensation.

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January 6, 2017

• Functions:-
• Role in Enzyme Action
• Role in Vitamin A Metabolism: Retinine reductase
• Role in Growth and Reproduction:
• lowers spermatogenesis in males, menstrual cycles are disturbed in females.
• Zinc deficiency due to phytate-rich diet may cause poor body growth, failure of full reproductive maturity and hypogonadism in humans
• Role in Wound Healing

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January 6, 2017

• Zinc deficiency:-
• Poor wound healing, lesions of skin, impaired spermatogenesis, hyperkeratosis, dermatitis and alopecia
• Reduction in number of T and B lymphocytes
• Macrophage function is retarded
• Depression, dementia and other psychiatric disorders
• Zinc binds with amyloid to form a plaque in Alzheimer's disease.

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Trace Minerals

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January 6, 2017

• Acrodermatitis enteropathica:-
• Recessive condition
• Zinc absorption is defective
• Characterized by acrodermatitis (inflammation around mouth, nose, fingers, etc.), diarrhea, alopecia (loss of hair in discrete areas), ophthalmoplegia and hypogonadism.

Trace Minerals

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January 6, 2017

• Zinc toxicity:-
• When intake is >1000 mg/day
• Seen in welders due to inhalation of zinc oxide fumes.
• Many rat poisons contain zinc compounds, which lead to accidental poisoning.
• Chronic toxicity may produce gastric ulcer, pancreatitis, anemia, nausea, vomiting and pulmonary fibrosis.
• Acute toxicity is manifested as fever, excessive salivation, headache and anemia.

Trace Minerals

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January 6, 2017

FLUORINE

• Fluoride is known to prevent caries. Caries is a Latin term, meaning "decay".(Teeth)
• Sources: solely derived in human from drinking water.
• Normal blood level: 4 µg/dl
• Requirements:
• Safe limit of fluorine is about 1 ppm in water (ppm = parts per million; 1 ppm = 1 gram of fluoride in million gram of water; this is equal to 1 mg per 1000 ml).
• Daily intake of fluoride should not exceed 3 mg as it is a toxic element. For an adult individual, the lethal dose is 2.5 gm.

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January 6, 2017

• In the pits and fissures of premolar and molar teeth, bacterial fermentation of residual food leads to acid production. The acid removes enamel and dentine to expose the pulp, leading to inflammation and toothache.
• Topical application of fluoride will result in a fluoroapatite layer on the enamel, which protects enamel from the decay by acid.

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January 6, 2017

• Absorption and Excretion:
• Absorbed by diffusion from the intestine
• Present in significant amounts in calcified tissues like bones and teeth
• Excreted mainly in the urine

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January 6, 2017

• FUNCTIONS:-
• Role in Tooth Development and Dental Health
• Role in Bone Development

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January 6, 2017

1. Role in Tooth Development and Dental Health:
1. It helps in tooth development, normal maintenance and hardening of dental enamel and prevention of “Dental caries”.
2. Incidence of dental caries are seen in areas where drinking water contains less than 0.5 PPM of fluorine
3. Greater than 1.2 PPM of fluorine in drinking water of infants/children may increase fluoride contents of the enamel and dentine, may reduce Ca deposition in those tissues and may cause Mottling of enamel, in newly erupted permanent teeth
4. Discoloration, corrosion and stratification of enamel including formation of pits are also observed.

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Trace Minerals

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January 6, 2017

2. Role in Bone Development:
1. Very small amount of fluorine in food and drinking water promote normal bone development, increases retention of Ca⁺⁺ and PO₄ and prevent old age osteoporosis.
2. High fluoride intakes may raise the fluoride content of bone, stimulate osteoblast activity and cause an abnormal rise in calcium deposition and increased density of bone.

Trace Minerals

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January 6, 2017

Fluorosis

• Fluorosis (Crippling disease) is More Dangerous than Caries
• Mitochondrial damage
• Inhibits particularly Mg ⁺⁺ dependent enzymes.
• 10 to 46 per cent reduction, in protein contents of various organs suggestive of inhibition of protein synthesis by fluorides
• Steroid production is also impaired
• Collagen content is found to be reduced and its biosynthesis adversely affected due to reduced proline uptake

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January 6, 2017

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January 6, 2017

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January 6, 2017

• Certain salts used in paan supari also have large content of fluoride
• Sources:- sea fish, cheese, tea and jowar
• Fluorosis is highly prevalent in areas where jowar is the staple diet
• Fluorinated toothpaste contains 3000 ppm of fluoride. Even ordinary toothpaste contains fluoride about 700 ppm.

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January 6, 2017

• Prevention of fluorosis:-
• Provide fluoride free water

(Nalgonda technique)

• Restriction of intake of jowar,
• Supplementation of vitamin C
• Regulation of fluoride containing toothpaste.

Trace Minerals

34

January 6, 2017

SELENIUM (Se)

• Selenium intake depends on the nature of the soil in which food crops are grown.
• Requirement: 50-100 microgram/day.
• Sources: Cereals
• Normal serum level: 50-100 microgram/dl.
• Biological forms of selenium which occur in animal body are selenium analogues of sulphur containing amino acids, viz. selenomethionine, selenocysteine and selenocystine.

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January 6, 2017

• Highest concentrations are found in testis, liver, kidneys and fingernails
• Absorbed mainly from the duodenum
• Main route of excretion of selenium: through urine.
• The UGA codon is acting as the codon for direct insertion of selenocysteine into selenium containing enzymes.
• Seleno-cysteine is directly incorporated into the protein during biosynthesis.
• So, Seleno-cysteine may be considered as the 21^st amino acid

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January 6, 2017

• It is necessary for normal development of spermatozoa (High conc.in testis)
• In mammals, Glutathione peroxidase (GP) is the important selenium containing enzyme. RBC contains good quantity of glutathione peroxidase.
• GP reduces hydroperoxide
• As antioxidant supplementary with Vit E

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January 6, 2017

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January 6, 2017

• Selenium has sparing effect on vitamin E

(Reduces Vit E requirement)

• Required for normal pancreatic function (digestion and absorption of lipids including Vit. E.)
• As a component of glutathione peroxidase
• Helps in retention of Vit. E in the blood plasma lipoproteins

Trace Minerals

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January 6, 2017

• Supplements of selenium probably protect against toxic effects of heavy metals (Ag, Hg, Cd)
• Toxicity in humans:- Selenosis
• Cause is occupation exposure in electronics, glass and paint industries.
• Manifests as chronic dermatitis, loss of hair and brittle nails
• No hepatotoxicity
• An early hall-mark of selenium toxicity is a garlicky breath, caused by exhalation of dimethyl selenide.
• Kaschinbeck disease is characterized by degenerative osteoarthrosis.

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January 6, 2017

• Naturally Occurring Selenium Deficiency in Humans
• Only reported in China
• It is k/a Keshan disease: Manifesting principally as cardiomyopathy.
• Role in HIV:
• Patients taking 200 μg of high selenium yeast daily, produces on an average 12% drop in blood virus levels
• Role in Hypothyroidism: 5'-de-iodinase

Trace Minerals

41

January 6, 2017

MANGANESE (Mn)

• Total body manganese is 15 mg
• Maximum concentration is in liver
• Requirement : 5 mg/day
• Sources: Nuts ,tea leaves
• Present mainly in RBCs in combination with several porphyrins and is transported in the plasma in combination with a β1-globulin called as transmanganin.

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42

January 6, 2017

• FUNCTIONS:-
• Role in Enzyme Action:
• as a ‘cofactor’ or as an activator of many enzymes
• Hexokinase, phosphoglucomutase, pyruvate carboxylase, arginase, isocitrate dehydrogenase (ICD), cholinesterase, lipoprotein lipase, enolase, leucine amino peptidase in intestine, phosphotransferases and 5-oxo-prolinase of kidneys
• Manganese and magnesium may replace one another in case of some of the enzymes.
• Mitochondrial form of Superoxide dismutase contains Mn⁺⁺ in its prosthetic group unlike the Cytosol form of the enzyme which contains Cu ⁺⁺ and Zn ⁺⁺.

Trace Minerals

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January 6, 2017

• Manganese is an integral part of glycosyl transferases, responsible for synthesis of glycoproteins and chondroitin sulfate.
• Also required for RNA polymerase activity.
• Role in Animal Reproduction
• Role in Bone Formation
• Mn ⁺⁺ plays a part in the synthesis or deposition of Mucopolysaccharides (MPS) in the cartilaginous matrices of long bones
• Mn ⁺⁺ deficiency causes significant lowering in the content of chondroitin SO₄

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January 6, 2017

4. Role in Fat Metabolism
1. “lipotropic effect” (stimulates FA synthesis and cholesterol synthesis.)
5. Role in Proteoglycan Synthesis
1. in glycoprotein and proteoglycan synthesis.

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45

January 6, 2017

MOLYBDENUM (Mo)

• Source :- Cereals and dry legumes
• Requirement: Adults: 0.5 mg/day
• Functions:-
• Role in Enzyme Action:
• Xanthine oxidase
• Mo deficiency causes depression of xanthine oxidase activity, increased excretion of xanthine and decreased uric acid excretion.

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January 6, 2017

• Molybdenosis
• Deficiency of Mo is associated with increased incidence of esophageal cancer.

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January 6, 2017

LITHIUM (Li)

• essential growth factor in tissue culture
• Higher concentrations are seen in brain
• Mean intake is 50 µg/day.
• Normal human skeletal muscles contain 2-200 nanogram/g of wet weight.
• Used in treating manic depressive psychosis (bipolar disorders)
• Therapeutically optimum concentration of Li in plasma is 7-10 microgram/ml, while 12 microgram is toxic
• Narrow safety margin so, constant monitoring

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Trace Minerals

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January 6, 2017

• Li causes inhibition of inositol phosphatase, leading to increased concentration of inositol phosphate in brain.
• Elevates serotonin levels and reduces catecholamines in brain tissue.
• Toxicity leads to hypothyroidism, hyperparathyroidism and kidney damage.

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January 6, 2017

THANK YOU

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January 6, 2017