MineralsTrace Elements

R. C. GuptaM.D. (Biochemistry)

Jaipur (Rajasthan), India

Some minerals essential for human beingsare required in minute quantities

These are known as trace elements

These are also known as micro-nutrients

The trace elements includeː

1. Iron

2. Iodine

3. Copper

4. Zinc

5. Cobalt

6. Manganese

7. Molybdenum

8. Chromium

9. Selenium

10. Fluorine

Iron

Total amount of iron in an adult humanbeing is 3.5-4.5 gm

Blood and blood-forming organs are thelargest reservoirs of iron

But small amounts of iron are present innearly every tissue

Important iron-containing compounds are:

• Haemoglobin

• Myoglobin

• Ferritin

• Haemosiderin

• Transferrin

• Cytochromes

• Iron-containing enzymes

About 70% of the body iron is present inhaemoglobin and 5% in myoglobin

Ferritin and haemosiderin, which are storageforms of iron, contain about 20% of the body iron

Transferrin, an iron carrier protein present inplasma, contains 0.1% of the body iron

The remaining iron is present in cytochromes andenzymes

Haem

Haemoglobin

Each subunit contains one iron atom

Haemoglobin is a tetramer made up of

four subunits

Myoglobin

Haem

Myoglobin is present in muscles

It is a monomer having one iron atom

Cytochromes

Cytochromes are present in respiratorychain, and support tissue respiration

Cytochrome P-450 and cytochrome b5

are components of microsomal hydroxy-lase system

Ferritin

Ferritin is one of the storage forms of iron

The protein portion of ferritin is known asapoferritin

Apoferritin combines with iron to formferritin

Ferritin is present in:

• Liver

• Spleen

• Bone marrow

• Brain

• Kidneys

• Intestine

• Placenta

The first step in the synthesis of ferritin isformation of apoferritin

Synthesis of apoferritin is induced by theentry of ferrous iron in the cell

This is followed by oxidation of ferrousiron to the ferric form

Ferric iron forms ferric hydrophosphatemicelles

Apo-ferritin Ferritin

80 Å

Ferric hydro-phosphate micelles

Ferric hydrophosphate micelles enter the protein shell to form ferritin

120 Å

Apoferritin is made up of 24 subunits oftwo types – H and L

Molecular weight of H subunits is 21,000and that of L subunits is 19,000

The proportion of H and L subunits inapoferritin differs in different tissues

The subunits are joined together to forma hollow sphere

Apoferritin

L Subunits

H Subunits

Ferric hydrophosphate micelles are

present in the hollow space in ferritin

When fully saturated, a molecule offerritinː

Contains 4,500 atoms of iron

Has a molecular weight of 900,000

Iron stored

inside ferritin

Haemosiderin is a granular iron-rich protein

Unlike ferritin, it is insoluble in water

The exact structure of haemosiderin is not known

Haemosiderin

Iron is first stored in the body in the form offerritin

As the iron stores increase, older ferritinmolecules aggregate to form haemosiderin

Some of the protein is degraded in thisprocess

Therefore, percentage of iron in haemo-siderin is higher than in ferritin

Normally, two-thirds of stored iron is inthe form of ferritin

The remaining one-third is stored in theform of haemosiderin

Transferrin is a carrier protein which transports iron in circulation

Free iron is toxic, and has a tendency to precipitate

These problems are overcome by combining iron with transferrin

Transferrin

Transferrin is a glycoprotein with a molecular weight of about 80,000

It is made up of a single polypeptide chain

One molecule of transferrin can transport up to two ferric atoms

Transferrin(By Emw - Own work, CC BY-SA 3.0,

https://commons.wikimedia.org/w/index.php?curid=9444665)

Transferrin present in plasma may be:

Diferric transferrin (carrying two ferric ions)

Monoferric transferrin (carrying one ferric ion)

Apotransferrin (carrying no ferric ions)

Transferrin carries iron to and fromvarious tissues through circulation

There are specific receptors for trans-ferrin on the cell membrane

The receptors are transferrin receptor 1(TfR1) and transferrin receptor 2 (TfR2)

TfR1 is synthesised by all iron-

requiring cells

It is present in high numbers on:

Immature erythroid cells

Rapidly dividing cells

Placental cells

TfR2 is synthesised by:

Liver cells

Haematopoietic cells

Duodenal crypt cells

TfR is a transmembrane glycoprotein madeup of two polypeptide chains

The polypeptide chains are joined by twodisulphide bonds

Each polypeptide possesses one bindingsite for transferrin

TfR has greater affinity for diferric transferrin than for monoferric or iron-free transferrin

Transferrin

Transferrin

receptor

Iron

Cell

membrane

Binding of iron-carrying transferrin to itsreceptor results in endocytosis of both,forming an endosome

Proton pumping into endosome changesthe conformation of transferrin and itsreceptor

The conformational change results inrelease of iron

Fe3+ is reduced to Fe2+ by ferrireductase

Iron is transported across the membraneof endosome into the cytoplasm

Transferrin receptor and apotransferrinare returned to the cell surface

Apotransferrin is released in plasma to becharged with iron again

Transferrin, once formed, can participatein 100-200 cycles of iron transport

Normal concentration of transferrin inplasma is 200-400 mg/dl

This amount of transferrin is capable ofcarrying 250-400 mg of iron/ dl of plasma

This is known as the total iron bindingcapacity of plasma

Normal plasma iron level is 50-175 µg/dl

This means that the iron binding capacityof plasma is nearly 30% saturated inhealthy subjects

Several enzymes require iron for theircatalytic activity

In some cases, iron forms an integral part of the enzyme molecule

In others, presence of iron is required forthe catalytic activity of the enzymes

Iron-containing enzymes

The iron-containing enzymes are mostlyconcerned with biological oxidation

Examples of such enzymes are catalase,peroxidase, aconitase, xanthine oxidase,succinate dehydrogenase etc

Iron is a transition metal, and can exist intwo redox states: Fe2+ and Fe3+

At the oxygen concentrations prevailing inthe body, the stable state of iron is Fe3+

But reduction of Fe3+ to Fe2+ is importantbecause most of the functions of irondepend upon the ferrous form

Functions of iron

Moreover, Fe2+ is the only form that canbe transported across membranes

Fortunately, the two forms are readilyinter-convertible

Functions

Transport of oxygen

Oxidative reactions

Tissue respiration

The most important function of iron is totransport oxygen in the body

This function is performed by haemo-globin

A similar function is performed in musclesby myoglobin

Transport of oxygen

Iron is a component of various oxido-reductase enzymes

As such, it plays a role in a number ofoxidative reactions

Oxidative reactions

As a component of cytochromes in theelectron transport chain, iron is involvedin tissue respiration

It is the iron component of cytochromes that accepts and donates electrons

Tissue respiration

Iron status depends upon the relative ratesof iron absorption and iron excretion

Iron absorption is the major mechanism formaintaining normal iron balance

Iron balance

Iron metabolism is said to occur within a closedsystem in the body

There is hardly any exchange of iron betweenman and his environment

The iron present in the body is continuouslyreutilized

Only a minute amount of iron is lost everydayfrom the body in the form of exfoliated cells

The faecal iron loss in 0.4-0.5 mg a day

The urinary iron loss is about 0.1 mg a day

About 0.2-0.3 mg of iron is lost daily from the skinalong with the exfoliated cells

Thus, the total iron loss is just under one mg aday

In premenopausal women, there are twoadditional routes of iron loss

About 20-25 mg of iron is lost withmenstrual blood in each cycle

This is equivalent to a daily loss of 0.7-0.8mg of iron

Iron balance is maintained by intestinalabsorption of iron

Iron lost is replenished by intestinal ironabsorption

Intestinal absorption of iron is affected by:

• Body iron stores

• Erythropoietic activity

• Degree of saturation of plasma transferrin

• The amount of dietary iron

• Valency of ingested iron (Fe+2 or Fe+3)

• Presence of other substances in the food

More iron is absorbed when:

• Body iron stores are low

• Erythropoietic activity is high

• Saturation of plasma transferrin is low

• Iron is ingested in ferrous form

Presence of the following in food increases iron absorption:

• Ascorbic acid

• Succinic acid

• Histidine

• Cysteine

Presence of the following in food decreases iron absorption:

• Phytates

• Phosphates

Iron can be absorbed from all segmentsof the small intestine

But presence and normal functioning ofstomach are essential

Achlorhydric and gastrectomized personsabsorb less iron as compared to normalpersons

Gastric enzymes and hydrochloric acid:

Release iron from iron-containing foods

Reduce ferric iron to the ferrous form

Enterocytes (mucosal cells of intestine) possess channels for:

Entry of iron on the luminal side

Exit of iron on the basolateral side

Iron is present in food as either inorganiciron or haem iron

Inorganic iron is about 90% of the totaland haem contains the remaining 10%

Bioavailability of haem iron is very high; itsabsorption is not hampered by other foodconstituents

Intact haem moiety is absorbed by entero-cytes via haem-carrier protein 1 (HCP1)

In the cells, iron is released from the proto-porphyrin ring by haem oxygenase-1

Inorganic iron is present in the diet mostlyin ferric form

It is reduced to ferrous form by duodenalcytocrome B (DcytB)

DcytB is present on the brush borderepithelium

Ascorbate may be an electron donor forthis reaction

Ferrous ions are transported into cells viadivalent metal transporter 1 (DMT1)

DMT1 is present on luminal membrane ofduodenal enterocytes

DMT1 is not a specific iron transporter

It also mediates transport of other divalentmetal cations such as Zn+2, Mn+2 and Cu+2

DMT1 is also present on the membrane of endosomes

It mediates iron transport from endosomes into the cytoplasm of the cell

The iron absorbed by the enterocyte, canbe stored within the cell as ferritin

Or it can be transported into circulationacross the basolateral membrane

Iron is transported across the basolateralmembrane via a specific transporter,ferroportin

Transport across basolateral membranerequires a change in redox state of iron

The intracellular Fe2+ form has to changeinto extracellular Fe3+ form

This conversion is brought about byhephaestin, a ferroxidase

All the iron that enters circulation is boundto transferrin

Affinity of transferrin for iron at normal pHof blood is extremely high

Transferrin delivers iron to the cells thatneed it

The main iron consumers are red cellprecursors

Iron homeostasis is maintained by regulating its absorption

It is believed that ferritin content of entero-cytes determines the absorption of iron

These cells are formed in the crypts ofLeiberkuhn

Regulation of iron absorption

Goblet cells

EnterocytesCrypt of

Leiberkuhn

Villus

Tip of villus

The enterocytes reach the tip of the villiand are shed off into the intestinal lumen

Their average life-span is three days

The function of ferritin in these cells is toblock the absorption of iron

The enterocytes formed during a period ofiron sufficiency are rich in ferritin

These cells will absorb very little iron duringtheir life-span

Moreover, when these are shed off, theiriron content will also be lost in faeces

Conversely, the cells formed during aperiod of iron deficiency are poor in ferritin

These cells absorb more iron and transfer itinto the plasma

Homeostatic mechanisms ensure that:

Systemic iron stores in the body areadequate

Each cell has an adequate amountof iron

The main sources of iron for cells are:

Iron absorbed by enterocytes

Iron stored in liver cells

Iron present in reticuloendothelial macrophages

Enterocytes, liver cells and macrophagesrelease iron through ferroportin

Ferroportin is the sole iron export channel

Iron export requires a change in the redoxstate of iron by ferroxidase

The ferroxidase is hephaestin in theduodenum and ceruloplasmin elsewhere

Macrophages are an important source ofiron for erythropoiesis

The macrophages obtain iron from agederythrocytes

Aged erythrocytes are engulfed by macro-phages in the reticulo-endothelial system

Their haemoglobin is broken up into haemand globin

The iron present in haem is released byhaem oxygenase-1

It is either stored within the macrophagesor is released into circulation

The iron released into plasma is taken upby transferrin

Most of the iron used for erythropoiesiscomes from haemoglobin recycling

The amount of iron recycled every day is10-20 times the amount absorbed by theintestine

Hepcidin is a peptide hormone synthesised in liver

Action of hepcidin is targeted at ferroportin

Hepcidin is a negative regulator of ferro-portin

Besides being an iron export channel,ferroportin also acts as hepcidin receptor

Role of hepcidin in iron homeostasis

Hepcidin binding to ferroportin causes itsinternalisation and lysosomal degradation

Loss of ferroportin decreases iron effluxfrom the cell

This leads to intracellular iron retention

As a result, plasma iron is decreased

Requirement

Only a small proportion of the dietary ironis normally absorbed

Hence, much larger amounts have to beprovided in diet than the requirement

Age and sex Requirement

Infants 6-10 mg/day

Children 10 mg/day

Adolescents 12 mg/day

Adult men and postmenopausal

women 10 mg/day

Premenopausal and lactating

women 15 mg/day

Pregnant women 30 mg/day

EMB-RCG

Iron is present in animal as well as plantfoods

Iron absorption from animal foods muchmore efficient than that from plant foods

On a mixed diet, healthy subjectsabsorb 5-10% of the dietary iron

Dietary sources

Animal sources of iron

Eggs FishMeat

Liver Kidney Heart

Plant sources of iron

Whole wheat Figs Dates

Beans SpinachNuts

Iron deficiency is widespread both in poor and in affluent countries

Iron deficiency is the commonest causeof anaemia throughout the world

Iron deficiency

Iron deficiency can result from:

Inadequate intake

Malabsorption

Blood loss

Inadequate intake is likely when the requirement is high e.g. in:

Infancy

Adolescence

Pregnancy

Malabsorption can be due to:

Steatorrhoea

Coeliac disease

Gastrectomy

Persistent blood loss can occur from:

Genital tract

Gastrointestinal tract

Hookworm infestation

The earliest change in iron deficiency is adepletion of body iron stores

Other changes follow progressively

Plasma transferrin saturation is decreased

Plasma iron is decreased

Microcytic hypochromic anaemia develops

Hemoglobin level falls

Poikilocytosis becomes evident

Severe and prolonged deficiency leads to:

Koilonychia

Angular stomatitis

Glossitis

Pharyngeal and oesophageal webs

Atrophic gastritis

Partial villus atrophy

Iron overload

Iron overload is much less common thaniron deficiency

Two types of iron overload syndromes areknown:

Haemosiderosis

Haemochromatosis

The excess iron is deposited in reticulo-endothelial cells

There is no tissue damage

Excess iron enters via parenteral route

This can be due to repeated bloodtransfusions e.g. in thalassaemia

Haemosiderosis

Haemochromatosis

Haemochromatosis can be primary or secondary

Primary haemochromatosis is genetic

The genes implicated in primary haemochromatosis are:

Hepcidin gene

Ferroportin gene

TfR2 gene

The genetic defect leads to excessiveintestinal absorption of iron

Excess iron is deposited in liver, heart,skin, pancreas and other endocrine glands

The condition is also known as bronzediabetes

The clinical abnormalities in haemochromatosis are:

• Hepatomegaly

• Cardiomegaly

• Congestive heart failure

• Hypogonadism

• Diabetes mellitus

• Bronze-coloured pigmentation of skin

Serum iron, ferritin and saturation of iron-binding capacity are increased in haemo-chromatosis

Phlebotomy and iron-chelating agentse.g. desferrioxamine are used to removeexcess iron

Secondary haemochromatosis may occur inalcoholic liver disease

Iron deposition is usually confined to hepatictissue

South African Bantus are known to develophaemochromatosis

It is due to heavy intake of iron present in analcoholic beverage brewed in iron vessels

Total iodine in an adult is 45-50 mg

About 10-15 mg is present in the thyroidgland

Muscles contain about 25 mg

About 5 mg is present in skin, 3 mg in the skeleton and 2 mg in liver

Iodine

The only known function of iodine is in thesynthesis of thyroid hormones

The thyroid gland synthesizes tri-iodo-thyronine (T3) and tetra-iodothyronine (T4)

These two are synthesized from iodineand tyrosine residues of thyroglobulin

Functions

The thyroid gland:

Actively takes up iodide ions from plasma

Oxidizes iodide to iodine

Incorporates iodine into tyrosine residues of thyroglobulin

Two DIT residues combine with each

other to form thyroxine (T4)

One MIT and one DIT residues combine to

form tri-iodo-thyronine (T3)

Iodine is absorbed from entire alimentarytract, particularly from small intestine

Iodine and iodate are converted intoiodide prior to absorption

Other mucous membranes and skin canalso absorb iodine

Absorption

Iodide absorbed from alimentary tract andelsewhere enters the circulation

About one third is taken up by the thyroidgland

The remainder is excreted, mainly by thekidneys

Small amounts of iodide are excreted insaliva, bile, milk, sweat and expired air

Plasma iodine level is 4-10 mg/dl

Only 10% of it is inorganic iodide

Organic iodine is present mostly in theform of thyroid hormones

Thyroid hormones are bound to someproteins (called protein bound iodine)

Daily requirement

Infants 40–50 µg/day

Children 70–120 µg/day

Adults 150 µg/day

Pregnant women 200 µg/day

Lactating women 250 µg/day

Iodine is present in water and soil

Foods, both animal and plant, obtainiodine from water and soil

Iodine content of foodstuffs depends

upon iodine content of water and soil

Dietary sources

Sea water is rich in iodine

Sea foods, e.g. fish, oysters, lobsters etc,are the best sources of iodine

As we go away from the sea, the iodinecontent of water and soil, and hence thatof the foodstuffs, decreases

Iodine deficiency is common in certainareas of the world

These areas constitute the so-calledgoitre belt

Sub-Himalayan region of India is a part ofgoitre belt since the iodine content of soiland water is poor in this region

Iodine deficiency

Iodine deficiency results in goitre(enlargement of thyroid gland)

Thyroid gland becomes hypertrophic in order to produce enough hormones from

the available iodine

The goitre is generally non-toxic (symptomless)

Goitre is endemic in the goitre belt areas

Goitre →

A severe deficiency of iodine can producehypothyroidism

Endemic goitre can be prevented byproviding iodized salt in the goitre belt

Iodized salt is prepared by addingpotassium iodate to common salt

Its iodine content should be 30 ppm (partsper million) at the manufacturing stage

It is supposed to be at least 15 ppm whenit reaches the consumer

Govt. of India has made iodisation of salt compulsory

About 60-100 mg of copper is present inan average adult

Relatively large amounts of copper arepresent in muscles (30-50 mg), bones(12-20 mg) and liver (9-15 mg)

Copper

Plasma copper level is 100-200 mg/dl

Nearly 90% of the plasma copper istightly bound to ceruloplasmin

The rest is loosely attached to albumin

Albumin is the major carrier of copper asit can easily release copper

Copper performs its functions in the formof copper-containing enzymes

These include cytochrome oxidase, super-oxide dismutase, monoamine oxidase,tyrosinase, dopamine b-hydroxylase etc

Ceruloplasmin also functions as ferro-xidase which oxidises Fe+2 to Fe+3

Functions

Copper is also required for:

Synthesis of haemoglobin

Formation of bones

Maintenance of myelin sheath of nerves

One third of dietary copper is normallyabsorbed, mainly from small intestine

Copper-binding P-type ATPase transferscopper from the lumen of the gut intoportal circulation

Copper-binding P-type ATPase is presentin intestinal mucosa and many other cells

Absorption

Albumin carries copper to liver

A different copper-binding P-type ATPaseis present in liver

This ATPase incorporates copper intoapo-ceruloplasmin

Adults require about 2.5 mg of copperdaily

Infants and children require about 0.05mg/kg of body weight

Daily requirement

Dietary sources of copper

Liver Kidney Meat

Nuts Legumes Raisins

Disorders of copper metabolism

Inherited disorders include:

Wilson’s disease

Menkes’ disease

Wilson’s disease is also known ashepato-lenticular degeneration

It is an autosomal recessive disease

Synthesis of ceruloplasmin is impaired inWilson’s disease

Wilson’s disease

There is no defect in the gene for cerulo-plasmin

Apoceruloplasmin is synthesized normally

The genetic defect involves incorporationof copper into apoceruloplasmin

There is congenital deficiency of copper-binding P-type ATPase in liver

This causes copper toxicity by impairing:

Incorporation of copper into apo-ceruloplasmin

Biliary excretion of copper

Large amounts of copper are deposited inliver, basal ganglia and around cornea

Serum copper and ceruloplasmin levelsare very low

Urinary excretion of copper is increased

This is an X-linked recessive disease

Copper-binding P-type ATPase isdeficient in intestinal mucosa and mostother tissues but not in liver

Copper accumulates in intestinal mucosa;it cannot be released into circulation

Menkes’ disease

Lack of absorption leads to deficiency ofcopper in the tissues

The deficiency causes:

Cerebral degeneration

Hypochromic microcytic anaemia

Steely and kinky hair

Serum copper and ceruloplasminlevels are elevated in:

• Pregnancy

• Infections

• Leukaemia

• Collagen diseases

• Myocardial infarction

• Cirrhosis of liver

The total amount of zinc in an averageadult is 1.3-2.1 gm

Its tissue distribution is very wide

Prostate, liver, kidneys, muscles, heart,skin, bones and teeth have zinc in highquantities

Zinc

Plasma zinc level is 50-150 µg/dl

Erythrocytes and leukocytes have ahigher concentration of zinc than plasma

Zinc is essential for normal growth andsexual development

It is required for synthesis of nucleic acids,which is essential for cell division andgrowth

In the form of zinc fingers, it is a part ofsome proteins which regulate transcription

Functions

Many enzymes require zinc for their catalytic activity such as:

• Alkaline phosphatase

• Carbonic anhydrase

• Carboxypeptidase

• Glutamate dehydrogenase

• Lactate dehydrogenase

• Malate dehydrogenase

• Alcohol dehydrogenase etc

Zinc is present in the b-cells of the isletsof Langerhans

It is required for the storage and releaseof insulin

Zinc is absorbed from the small intestine

Copper, cadmium and calcium interferewith the absorption of zinc

Phytates also retard zinc absorption byforming an insoluble complex with zinc

Absorption

Daily requirement

Age and sex Requirement

Infants 2-3 mg/day

Children 5-8 mg/day

Adult men 12 mg/day

Adult women 10 mg/day

Pregnant women 12 mg/day

Lactating women 12 mg/day

Meat

Dietary sources of zinc

Liver Kidney

Fish Eggs

Milk

Fish

Yeast

Whole grain cereals

Dietary zinc deficiency may occur invegetarians taking refined wheat flour astheir staple diet

It can also occur in acrodermatitis entero-pathica

Zinc deficiency

Zinc deficiency causes:

• Retardation of growth

• Dwarfism

• Delayed puberty

• Hypogonadism

A milder deficiency may

cause:

• Poor wound healing

• Impaired perception of taste

About one mg of cobalt is present in anaverage adult

It is distributed chiefly in liver, kidneys andbones

Cobalt is present almost entirely as aconstituent of vitamin B12

Cobalt

Inorganic cobalt doesn’t perform anyfunction in human beings

Inorganic cobalt is not absorbed from thegut; injected cobalt is rapidly excreted

Cobalt functions solely as a component ofvitamin B12

It must be provided in the diet as vitaminB12

About 12-20 mg of manganese is presentin an average adult

Liver, pancreas and kidneys containrelatively more manganese than othertissues

Manganese

Manganese is present mainly in themitochondria and nuclei of the cells

Manganese is absorbed from the smallintestine

Less than 5% of the ingested manganeseis normally absorbed

Manganese is required for:

• Formation of matrix of bones and cartilages

• Normal reproduction

• Normal functioning of central nervous system

• Stabilizing the structure of nucleic acids

A number of enzymes require manganese as a cofactor such as:

• Superoxide dismutase

• Arginase

• Acetylcholine esterase

• RNA polymerase

• Carboxylases

• Glycosyl transferases

The daily requirement of manganese is2-5 mg

Whole-grain cereals, legumes, nuts,green vegetables and fruits are goodsources of manganese

Molybdenum is present in very smallamounts in human beings, mainly in liverand kidneys

It is a component of xanthine oxidase,aldehyde oxidase and sulphite oxidase

Sulphite oxidase converts sulphite andsulphur dioxide into sulphate

Molybdenum

The exact requirement for molybdenum isunknown

An average diet provides 75-100 µg ofmolybdenum a day

Molybdenum deficiency is unknown inhuman beings

Excessive intake of molybdenum maycause copper deficiency

The total amount of chromium in anaverage adult is about 6 mg

It is widely distributed in the body

Chromium is a constituent of glucosetolerance factor (GTF)

Chromium

GTF is a low molecular weight peptide

GTF binds to insulin receptor andpotentiates the actions of insulin

A relationship has been shown betweenchromium deficiency and glucoseintolerance

Absorption of chromium is less than 1%

Stainless steel utensils contain chromiumwhich can be absorbed

Chromium intake is about 0.35 mg/day inmen and 0.25 mg/day in women which isadequate

Excess chromium can be toxic

Selenium content of normal adult humansvaries widely

Values from 3 mg to 15 mg have beenreported in different geographical areas

About 30% of the total body selenium ispresent in the liver, 30% in muscles, 15%in kidneys, and 10% in blood

Selenium

Most of the selenium present in tissues ispresent in proteins (selenoproteins)

Selenium performs its functions in theform of selenoproteins, many of whichare enzymes

Four different glutathione peroxidaseshave been identified, all of which containselenium

Glutathione peroxidase (GPx) is a part ofthe anti-oxidant defence system

GPx can break down hydrogen peroxideand fatty acid hydroperoxides

Both these are toxic compounds

Thus, the major role of selenium is as ananti-oxidant

In this function, it complements the role of vitamin E

Another role of selenium is in iodinemetabolism

Three different iodo-thyronine deiodinaseshave been identified

These convert thyroxine (T4) into the moreactive tri-iodo-thyronine (T3)

All the three are selenium-containingenzymes

The two major forms of selenium in foodare selenomethionine and selenocysteine

Selenomethionine is found mainly in plant foods and selenocysteine in animal foods

Their absorption is highly efficient

The main site of absorption is duodenum

Absorption and excretion

Selenium homeostasis is maintainedprimarily through excretion

Selenium is excreted via urinary andalimentary tracts

Urinary excretion is the primary route ofregulation under normal conditions

Different selenium requirements havebeen recommended in different countries

In India, the recommended intake is 40μg/day for adults of both sexes

The role of selenium deficiency in humanbeings came to the fore in 1979

Selenium deficiency was correlated withKeshan disease and Kashin-Beck diseasein China

These diseases were found in areas wheresoil is severely deficient in selenium

Keshan disease results in cardiomegaly,congestive heart failure and cardiacnecrosis

Kashin-Beck disease results in severeosteoarthritis, and degeneration ofchondrocytes and nerves

Selenium supplementation was found toprotect people from these diseases

Fluorine naturally occurs as thenegatively charged fluoride ion

Only small amounts are present inhuman beings (about 2.5 gm in adults)

More than 95% of fluoride is present inbones and teeth

Fluorine

Fluoride is not physiologically essentialbecause it doesn’t perform any function

Still, it is considered as essential becauseof its role in prevention of dental caries

Dental caries is a chronic disease causedby cariogenic bacteria

Cariogenic bacteria are naturally presentin the oral cavity

They metabolize carbohydrates intoorganic acids (pyruvic and lactic acids)

These acids can dissolve tooth enamel

This produces cavities in teeth (dentalcaries)

Dental caries

Teeth are made up mainly of calciumhydroxyapatite

Fluoride ions displace the hydroxyl ionsforming fluoroapatite

This hardens the tooth enamel, andmakes it resistant to dissolution

Fluoride ions also decrease acidproduction by inhibiting bacterial enzymes

The fluoride content of most foods is verylow

Exceptions are tea, grape juice andmarine fish

Some fruits and vegetables may acquirefluoride from fluoride-based pesticides

Main source of fluoride is drinking water

In tropical countries like India, waterintake is relatively high

Drinking water provides enough fluoride ifits fluoride content is 0.5-0.8 ppm (partsper million)

If fluoride content of water is low, dentalcaries becomes a public health problem

In such areas, fluoride must be added tothe source of drinking water (fluoridation)

The aim is to raise the fluoride content to0.5-0.8 ppm

Excess of fluoride in drinking water isharmful

If the fluoride content of water exceeds1.5 ppm, it can cause fluorosis

If the excess is mild, only the teeth areaffected (dental fluorosis)

If the excess is severe, the bones areaffected (skeletal fluorosis)

In early stage, the teeth appear mildlydiscoloured

Later on, stains ranging in colour fromyellow to dark brown appear on teeth

The surface of teeth becomes irregularwith noticeable pits

Dental fluorosis

Moderate fluorosis Severe fluorosis

Dental fluorosis

Normal teeth Mild fluorosis

Prolonged intake of excessive fluorideaffects the bones

The bones of vertebral column, pelvis andlimbs get deformed

There is calcification of ligaments andtendons, immobility and muscle wasting

Skeletal fluorosis

Skeletal fluorosis can also result inneurological problems

Neurological problems are caused byspinal cord compression

Skeletal fluorosis

Fluorosis occurs in certain areas where fluoride content of water is high

There are several such areas in the world

There are some high-

fluoride areas in India also

Defluoridationof drinking

water is required in such areas