Minerals

From Essentials of Medical Biochemistry by R.C. Gupta

Of the large number of minerals present in nature,
only a few are essential for human beings

Some of these are required in relatively large

quantities, and are known as principal elements or
macronutrients

These include calcium, phosphorus, magnesium,

sodium, potassium, chlorine and sulphur

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Some minerals are required in minute quantities,
and are known as trace elements or micro-
nutrients

These include iron, iodine, copper, zinc, cobalt,

manganese, molybdenum, chromium, selenium
and fluorine

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 Calcium

 Calcium is the most abundant mineral in human

beings

 Total calcium in an average adult is about 1,000

gm of which nearly 99% is present in bones and
teeth

 The rest (about 10 gm) is distributed in various

tissues and body fluids
 Muscles and nerves have relatively more
calcium than other tissues

 Calcium is present in bones mainly in the form

of calcium phosphate

 Small amounts of carbonate, hydroxide,

fluoride, citrate and other salts of calcium are also
present
 Calcium phosphate is first deposited in an
amorphous form which is later converted into
crystalline form

 The crystalline form is known as hydroxyapatite,

and its rough composition is Ca10(PO4)6(OH)2

 The crystals are rod-shaped

 There is a continuous exchange of calcium

between bones and extracellular fluid
 Concentration of calcium in intracellular and
extracellular fluids is delicately regulated

 The concentration of calcium in plasma (or serum)

is 9-11 mg/dl (4.5-5.5 mEq/L)

 About 50% of this is bound to proteins, and can

not diffuse through capillaries (protein-bound or
non-diffusible calcium)
 About 5% is associated with organic anions e.g.
citrate, and is diffusible

 The remaining 45% is free ionized calcium, and

is freely diffusible

 Almost all the physiological functions of calcium

are performed by ionized calcium
 Functions

Neuro Excitabil
Format Excitab
ity and
Coag Actio
ion of ility and muscul
contracti ulatio n of
bones conduc ar lity of
and tivity of transm myocard
n of horm
teeth nerves ission ium blood ones
 Formation of bones and teeth

 A major function of calcium is to form bones and

teeth

 Calcium phosphate is deposited around collagen

fibres in the zone of ossification

 It is first deposited in an amorphous form which

changes later into hydroxyapatite crystals
 Osteoblasts mineralize the bones and
osteoclasts remove minerals from the bones

 In growing age, osteoblastic activity is more than

the osteoclastic activity leading to skeletal growth

 In adults, the activities are balanced leading to a

continuous remodelling of the bones
 Excitability and conductivity of nerves

 Excitability of nerves depends upon a number of

cations including Ca++

 A raised plasma Ca++ level decreases, and a

lowered plasma Ca++ level increases the
excitability of nerves

 Transmission of impulses across synapses

occurs due to release of neurotransmitters which
requires Ca++
 Neurotransmitters are present in the cell inside
synaptic vesicles

 There are two pools of synaptic vesicles, reserve

pool and releasable pool

 In the reserve pool, a synaptic vesicle is bound to

actin filaments through a protein, synapsin I
(dephosphorylated)
 Release of Ca++ activates calmodulin (CaM)
kinase II which phosphorylates synapsin I

 This leads to dissociation of the synaptic vesicle

from actin filaments

 Synaptic vesicle moves to releasable pool from

where it releases the neurotransmitter molecules
by exocytosis
 Neuromuscular transmission

 Neuromuscular transmission occurs through

release of acetylcholine from the motor endplate

 This occurs in the presence of calcium ions

 Excitability and contractility of
myocardium

 The rhythmic generation of impulses in heart

and contraction of heart muscle also require calcium
ions

 An increase in the concentration of ionized

calcium increases cardiac contractility and vice
versa
 Coagulation of blood

 Ionized calcium is one of the coagulation factors

 Coagulation of blood occurs by a cascade of

reactions

 Calcium ions are required in most of these

reactions

 Many of the anticoagulants used to prevent in

vitro coagulation of blood, e.g. oxalate, citrate,
EDTA etc, act by binding calcium ions
 Action of hormones

 Ionized calcium acts as a second messenger

for some of the hormones

 Moreover, the secretion of hormones which are

stored in granular form also requires the
presence of calcium ions
 Absorption

 Absorption of calcium occurs by an active

uptake system in the upper part of small intestine

 Normally, 10-20% of the dietary calcium is

absorbed
The absorption is affected
by:
pH

Calcium : phosphorus ratio

Proteins

Vitamin D and parathormone

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 pH

 A relatively low pH increases solubility of calcium

salts

 This increases calcium absorption

 Calcium : phosphorus ratio

 Since calcium and phosphorus are absorbed

together, they must be present in the diet in a proper
ratio

 The ideal ratio is 1:1 but absorption can occur

satisfactorily as long as the ratio lies between 1:2
and 2:1
 Proteins

 Presence of proteins and amino acids in the

food together with calcium facilitates the absorption
of calcium
 Vitamin D and parathormone

 Vitamin D and parathormone play an important

role in the metabolism of calcium

 Cholecalciferol is converted into its active

metabolite, 1,25-dihydroxycholecalciferol with the
help of parathormone
 1,25-Dihydroxycholecalciferol acts on intestinal
mucosa and induces the synthesis of:
• Calcium-binding protein
• Calcium- dependent ATPase
• Alkaline phosphatase

 These are required for the active absorption of

calcium

 As calcium is absorbed, plasma calcium level

rises
 When plasma calcium rises above normal, it
causes feedback inhibition of parathormone
secretion

 This switches off the series of reactions

responsible for raising the plasma calcium level

 Thus, vitamin D and parathormone act in concert

to regulate calcium absorption and the plasma
calcium level
 Cholecalciferol

LIVER Hydroxylase

25-Hydroxycholecalciferol

KIDNEY Hydroxylase Å Parathormone Parathyroid

glands
1, 25-Dihydroxycholecalciferol
INTESTINAL
MUCOSA Induction

Calcium-binding protein
++
Ca -dependent ATPase –
Alkaline phosphatase

INTESTINAL
MUCOSA
Release into circulation
Calcium absorption Plasma calcium
 Daily requirement

Age Requirement

Infants 400-600 mg/day

Children 800 mg/day

Adolescents 1200 mg/day

Adults 800 mg/day

Pregnant and
lactating women 1200 mg/day

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Sources
Milk
Cheese
Eggs
Figs
Nuts
Beans
Lentils
Cabbage
Cauliflower
 Abnormal serum calcium levels

Serum calcium level may rise or fall in some

pathological conditions

An increase in serum calcium level is

known as hypercalcaemia

A decrease in serum calcium level is known as

hypocalcaemia

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 Hypercalcaemia occurs in:
• Hyperparathyroidism
• Hypervitaminosis D
• Bone cancer
• Multiple myeloma
• Leukaemia
• Polycythaemia
• Milk-alkali syndrome
• Sarcoidosis
• Idiopathic infantile hypercalcaemia
 Hypocalcaemia occurs in:
• Hypoparathyroidism
• Rickets
• Osteomalacia
• Steatorrhoea
• Chronic renal failure
• Nephrotic syndrome
 If serum calcium level remains elevated over a
long period, calcium may get deposited in soft
tissues such as kidneys, liver, arteries etc

 A sudden decrease in serum calcium may cause

tetany (involuntary contraction of skeletal muscles)
 Phosphorus

Next to calcium, phosphorus is the most

abundant mineral in human beings

About 700 gm of phosphorus is present in an

average adult

Nearly 80% of it is present in bones and teeth

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The remainder is distributed all over the body

Nerves and muscles are particularly rich in

phosphorus

Phosphorus is mainly an intracellular mineral

Serum inorganic phosphorus level is 2.5 - 4.0

mg/dl in adults and 4 - 7 mg/dl in children

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The product of serum calcium concentration
(mg/dl) and serum inorganic phosphorus
concentration (mg/dl) remains nearly constant

Adults
Serum calcium X serum inorganic phosphorus =40

Children
Serum calcium X serum inorganic phosphorus =50
 Functions

Forma Format Role Forma Forma

ion of Forma Maint
tion of in tion of tion of
high- tion of enan
bones energy
meta nuclei nervo
memb ce of
and compo bolis c us
ranes pH
teeth unds m acids tissue
 Formation of bones and teeth

 As seen earlier, calcium phosphate is the

principal salt in bones and teeth

 Formation of bones and teeth is one of the major

functions of phosphorus
 Formation of high-energy compounds

 Phosphorus is a constituent of most of the high-

energy compounds in our body e.g. ATP, creatine
phosphate, phosphoenol pyruvate etc
 Role in metabolism

 Phosphorus is a constituent of many coenzymes

e.g. FMN, FAD, NAD, NADP, thiamin pyro-
phosphate, pyridoxal phosphate and coenzyme A

 Phosphorus plays an important role in metabolic

reactions in the form of these coenzymes
 Moreover, phosphorus plays a unique role in the
metabolism of carbohydrates

 Carbohydrates have to be phosphorylated

before they can enter any metabolic pathway
 Formation of nucleic acids

 Phosphorus is required for the formation of

nucleotides which, in turn, form nucleic acids
 Formation of membranes

 Phosphorus participates in the formation of bio-

membranes in the form of phospholipids
 Formation of nervous tissue

 Phosphorus also takes part in the formation of

nervous tissue in the form of phospholipids
 Maintenance of pH

 Inorganic phosphorus exists as HPO4-2 and

H2PO4- which constitute a buffer pair and help in the
maintenance of pH

 Phosphate buffer is more abundant in

intracellular fluid
 Absorption

 Phosphorus is absorbed from the small intestine

along with calcium

 If calcium absorption is normal, so will be that of

phosphorus
 Daily requirement

Age Requirement

Infants 250-400 mg/day

Children 800 mg/day

Adolescents 1200 mg/day

Adults 800 mg/day

Pregnant and
lactating women 1200 mg/day

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 Dietary sources

 Phosphorus is widely distributed in foodstuffs

 If calorie and protein intakes are sufficient, a

dietary deficiency of phosphorus is unlikely to occur

 Milk, cheese, eggs, meat, nuts and beans are

particularly good sources of phosphorus
 Abnormal serum phosphorus levels

 An increase in serum inorganic phosphorus level

is known as hyperphosphataemia

 A decrease in serum inorganic phosphorus level is

known as hyperphosphataemia
Hyperphosphataemia occurs in:
• Chronic renal failure
• Hypoparathyroidism
• Hypervitaminosis D
• Acromegaly
• Diabetes mellitus
Hypophosphataemia occurs in:
• Rickets
• Osteomalacia
• Hyperparathyroidism
• Steatorrhoea
• Fanconi syndrome and
• Familial hypophosphataemic rickets
 Familial hypophosphataemic rickets is also known
as renal rickets or vitamin D-resistant rickets

 Renal rickets is an inherited disorder (X-linked

dominant) in which renal tubular reabsorption of
phosphate is greatly decreased
 Magnesium

The total magnesium in an average adult is about

20 gm

Bones contain about 70% of the total body

magnesium

The remainder is present in other tissues and

body fluids e.g. muscles, blood, CSF etc

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Serum magnesium level is 2 - 3 mg/dl

Concentration in intracellular compartment is

higher than that in extracellular compartment

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Functions

Excitability of
nerves

Cofactor for
enzymes

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 Excitability of nerves

Together with some other cations, magnesium

ions also affect the excitability of nerves

A low magnesium level increases the excitability,

and a high magnesium level decreases the
excitability

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 Cofactor for enzymes

Magnesium is a cofactor for all the enzymes

requiring ATP

ATP participates in biochemical reactions as Mg+

+
- ATP complex

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 These include enzymes involved in the
metabolism of:
• Carbohydrates
• Lipids
• Amino acids
• Purines
• Pyrimidines
 Examples are:
• Hexokinase
• Phosphofructokinase
• Pyruvate kinase
• Thiokinase
• Mevalonate kinase
• Squalene synthetase
• Glutamine synthetase
• Carbamoyl phosphate synthetase
• PRPP synthetase
 Absorption

 Magnesium is absorbed from the small intestine

 The extent of absorption depends on the

magnesium content of the diet and is independent of
the requirement

 On an average diet, about half of the ingested

magnesium is absorbed
 The absorption may increase on a low-
magnesium diet, and may fall on a high- magnesium
diet

 The regulation of magnesium balance is the

function of kidneys

 Aldosterone plays a role in the renal regulation

 A high aldosterone level decreases the tubular

reabsorption of magnesium
 Daily requirement

Age and sex Requirement

Infants 60-70 mg/day

Children 150-250 mg/day

Adult men 350 mg/day

Adult women 300 mg/day

Pregnant and
lactating women 450 mg/day

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 Dietary sources

 Nuts, beans, wheat, milk, eggs, orange and

spinach are good sources of magnesium

 Almond is particularly rich in magnesium

 Abnormal serum magnesium levels

 Serum magnesium level is decreased (hypo-

magnesaemia) in chronic alcoholism,
chronic diarrhoea, hyperparathyroidism and
aldosteronism

 A high serum magnesium level (hyper-

magnesaemia) is commonly seen in renal failure
 Sodium

Total amount of sodium in an average adult is

about 60 gm

About 20 gm is present in bones

The rest is distributed in other tissues

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Sodium is the major cation of the extracellular
fluids

Plasma sodium level is 310-340 mg/dl or

136-145 mEq/L

Other extracellular fluids also have a high

concentration

The intracellular fluid contains only about 10

mEq/L

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Functions

Maintenance of osmotic pressure

Maintenance of pH

Nerve excitability and conduction

Active transport

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 Maintenance of osmotic pressure

 Being the major cation of extracellular fluids,

sodium plays on important role in maintaining the
osmotic pressure of extracellular fluids

 Osmotic pressure depends upon the number of

solute particles and not on their size

 Sodium ions outnumber all the other solute

particles in extracellular fluids
 Maintenance of pH

 In the form of sodium bicarbonate, it is a

component of the bicarbonate-carbonic acid buffer
which is a major buffer of the extracellular fluids

 Renal excretion of hydrogen ions in exchange for

sodium ions is also important in maintaining the
pH of body fluids
 Nerve excitability and conduction

 Maintenance of normal excitability of nerves and

conduction of nerve impulses are also important
functions of sodium

 Cations and anions are so distributed across the

cell membrane of nerve fibres that the exterior of the
membrane is slightly electropositive in relation to
the interior
 This potential difference is known as the resting
potential

 When a stimulus is applied to the nerve, the

stimulated area immediately becomes permeable
to sodium ions which move into the interior of the
nerve fibre

 The interior becomes electropositive in relation to

the exterior
 Thus, a nerve impulse is generated

 Transmission of the nerve impulse also occurs

due to influx of sodium ions along the entire length
of the nerve fibre
 Active transport

 Several compounds enter the cells against their

concentration gradient by active absorption

 Sodium pump ejects sodium ions from the interior

of the cell to the exterior

 It is linked with the active absorption of glucose,

galactose and some amino acids
 Absorption

 Sodium enters gastrointestinal tract through

ingested food and through digestive secretions

 The latter is a far more abundant source as

compared to dietary intake

 Almost all the sodium is absorbed from the gastro-

intestinal tract
 The absorption occurs from the entire length of
the small and large intestines

 Concentration of sodium in intestinal lumen is far

greater than that inside the mucosal cells

 Sodium diffuses from the lumen into the cells

down its concentration gradient

 The intracellular sodium is actively transported

into blood by the sodium pump
 Pumping of Na+ into blood keeps intracellular
concentration of sodium in the mucosal cells at a
low level

 More sodium diffuses from the intestinal lumen

into the mucosal cells
 Requirement

 There has been considerable controversy about

the daily requirement of sodium

 The requirement depends upon daily loss of

sodium

 The loss depends upon the climate

 In a tropical country like India, a daily intake
of 4-6 gm of elemental sodium or 10-15 gm of
sodium chloride is sufficient to maintain sodium
balance

 A direct relationship exists between excessive

sodium intake and prevalence of hypertension

 We have to guard against excessive intake

rather than deficiency
 Dietary sources

 Table salt (sodium chloride) is one of the chief

sources of sodium in our daily diet

 Baking powder (sodium bicarbonate) can also

contribute significant amounts
 Meat, fish, fowl, eggs, milk, cheese and cereals
are rich in sodium

 Carrot, radish, cauliflower, spinach, turnip,

legumes and nuts are also good sources of
sodium
 Abnormal serum sodium levels

 Sodium metabolism is controlled by adreno-

cortical hormones

 Mineralocorticoids, such as aldosterone, are the

most potent in this regard followed by
glucocorticoids and sex hormones
 These hormones cause retention of sodium and
loss of potassium from the body

 Therefore, abnormal serum sodium levels occur

in adrenocortical disorders

 Excessive loss of sodium in gastrointestinal

secretions and urine can also affect the serum
sodium level
 Hyponatraemia (low serum sodium) occurs in
adrenocortical insufficiency, severe diarrhoea,
chronic renal disease, excessive sweating etc

 Hyponatraemia may also occur due to dilution of

plasma when dehydrated patients are rehydrated
with salt-free fluids
 Hypernatraemia (high serum sodium) occurs in
adrenocortical hyperactivity, prolonged steroid
therapy and dehydration

 In dehydration, hypernatraemia occurs due to

haemoconcentration
 Potassium

Total amount of potassium in an average adult is

about 140 gm

Potassium is the chief cation of the intracellular

compartment, and is present in all cells

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The potassium content of intracellular fluid is
about 140 mEq/L

Potassium concentration in extracellular fluid is

only about 5 mEq/L

Serum potassium level is 3.5-5 mEq/L

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Functions

Maintenance of osmotic pressure

Maintenance of pH

Nerve excitability and conduction

Cofactor for enzymes

Active transport

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 Maintenance of osmotic pressure

 Potassium is involved in the maintenance of

osmotic pressure within the cells in the same way
as sodium does in extracellular compartment

 Nearly half the osmolarity of intracellular fluid is

due to potassium
 Maintenance of pH

 Potassium, in the form of KH2PO4 and K2HPO4,

helps to maintain the pH of intracellular fluid
 Nerve excitability and conduction

 Together with sodium, potassium plays a role in

maintaining the normal excitability of nerves and in
the conduction of nerve impulses

 It also affects the excitability and contractility of

muscles, particularly heart muscles

 Marked alterations in serum potassium level

often cause serious abnormalities in the functioning
of the heart
 Cofactor for enzymes

 Potassium functions as a cofactor for some

enzymes e.g. pyruvate kinase
 Active transport

 Along with sodium, potassium is also involved in

active transport

 Sodium pump is involved in energy-dependent

active transport of glucose, galactose, amino acids
etc

 It is really a sodium-potassium pump as it

causes efflux of sodium and influx of potassium
 Absorption

 Potassium absorption occurs down the

concentration gradient from small intestine as well
as large intestine
 Requirement

 The exact potassium requirement is not known

with certainty

 A daily intake of 4 gm is sufficient to maintain

potassium balance
 Dietary sources

 Potassium is very widely distributed in foodstuffs

 Meat, fish, fowl, cereals, vegetables, apricots,

peaches, oranges and pineapples are rich in
potassium
 Abnormal serum potassium levels

 A decrease in serum potassium level is known

as hypokalaemia

 An increase in serum potassium level is known

as hyperkalaemia

 Both affect nervous system, heart and muscles,

and produce characteristic ECG changes
Hypokalaemia occurs in :
• Adrenocortical hyperactivity
• Prolonged steroid therapy
• Diarrhoea
• Wasting diseases
• Metabolic alkalosis
• Familial periodic paralysis
• After insulin injection
• Prolonged use of thiazide diuretics
 Hypokalaemia can cause:
• Irritability
• Muscular weakness
• Tachycardia
• Cardiac dilatation
• Cardiac arrest
 Hypokalaemia also produces characteristic
electrocardiographic changes :
• Flattened or inverted T waves
• Depressed ST segment

 These changes are valuable in the

diagnosis of potassium deficit
 Hyperkalaemia occurs in:
• Adrenocortical insufficiency
• Renal failure
• Dehydration
• Indiscriminate intravenous potassium
therapy
 Hyperkalaemia causes:
• Mental confusion
• Numbness and tingling
• Muscular weakness and paralysis
• Bradycardia
• Peripheral circulatory failure
• Cardiac arrest
 Characteristic electrocardiographic changes are:
• Lengthening of P-R interval
• Widening of QRS complex
• Elevation of T waves
 Chlorine

The total amount of chlorine in an average adult

is about 80 gm

Chlorine, in the form of chloride ions, is the chief

anion of extracellular compartment

Normal serum chloride level is 100-106 mEq/L

(355-375 mg/dl)

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The chloride content of cerebrospinal fluid is 120
to 130 mEq/L

The interstitial fluid contains about 110 mEq/L

The intracellular fluid contains only about 4

mEq/L

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Functions

Maintenance of osmotic pressure

Maintenance of pH

Formation of hydrochloric acid

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 Maintenance of osmotic pressure

 Chloride ions are present in a high concentration

in extracellular fluids

 Along with sodium ions, they play an important

role in maintaining the osmotic pressure of extra-
cellular fluids
 Maintenance of pH

 Chloride ions help in maintaining the pH of blood

by the mechanism of chloride shift
 Formation of hydrochloric acid

 Hydrochloric acid is an important constituent of

gastric juice

 Chloride ions are required for its formation

 Absorption

 Chloride is absorbed passively down its

concentration gradient in the upper portion of small
intestine

 In distal ileum and colon, chloride ions are

absorbed in exchange for bicarbonate ions
 Requirement

 Chloride is commonly present in food as sodium

chloride

 Therefore, sodium and chloride intakes are

parallel

 If daily requirement of sodium is met, so will be

that of chloride
 Dietary sources

 Table salt is the most abundant source of

chloride in our daily diet

 Foods having sodium also provide chloride e.g.

meat, fish, fowl, eggs, milk, cheese, cereals etc
 Abnormal serum chloride levels

 With a few exceptions, changes in serum

chloride level are parallel to those in serum
sodium level

 Serum chloride level is raised (hyperchloraemia)

in dehydration, respiratory alkalosis, metabolic
acidosis and adrenocortical hyperactivity
 Serum chloride level is decreased
(hypochloraemia) in severe vomiting, prolonged
gastric suction, respiratory acidosis, metabolic
alkalosis and Addison’s disease
 Sulphur

About 100 gm of sulphur is present in an average

adult

Inorganic sulphur, in the form of sulphate ions, is

present in very small amounts

Organic sulphur is the predominant form of

sulphur in the body

It is present in most proteins in the form of

sulphur-containing amino acids

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Functions

Component of proteins

Component of
mucopolysaccharides

Constituent of many vitamins

Detoxification of many harmful

substances
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 Sulphur is a component of most of the proteins in
the form of cysteine and methionine

 The sulphydryl (–SH) groups of cysteine residues

stabilize the structure of proteins by forming
disulphide bonds

 They are also essential for the biological activity of

many proteins, particularly enzymes
 Several mucopolysaccharides, e.g. heparin,
chondroitin sulphate and keratan sulphate, contain
sulphur

 Sulphur is a constituent of many vitamins e.g.

thiamin, biotin, lipoic acid etc

 Active form of pantothenic acid, i.e. coenzyme

A and acyl carrier protein, also contain sulphur
 Detoxification of many harmful substances is
done in liver by conjugation reactions

 Several such substances are conjugated with

sulphate
 Absorption

 Sulphur is absorbed from the intestine mainly in

the form of sulphur-containing amino acids

 Absorption of inorganic sulphate is very poor

 Requirement

 The daily excretion of sulphur is about 5 gm in

average adults

 Most of it is derived from proteins

 If protein intake is adequate, it will provide

sufficient sulphur as well
 Dietary sources

 It is the sulphur of the proteins that meets our

sulphur requirements

 Therefore, protein-rich foods, e.g. eggs, milk,

cheese, meat, fish, nuts and legumes, are the main
sources of sulphur in our daily diet
 Iron

Total amount of iron in an adult human being is

3.5-4.5 gm

Blood and blood-forming organs are the largest

reservoirs of iron in our body

But small amounts of iron are present in nearly

every tissue

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 Important iron-containing compounds are:
• Haemoglobin
• Myoglobin
• Ferritin
• Haemosiderin
• Transferrin
• Cytochromes
• Iron-containing enzymes
About 70% of the body iron is present in
haemoglobin and 5% in myoglobin

Ferritin and haemosiderin, which are storage

forms of iron, contain about 20% of the body iron

Transferrin, an iron carrier protein present in

plasma, contains 0.1% of the body iron

The remaining iron is present in cytochromes and

enzymes

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 Haemoglobin

 Haemoglobin is a tetramer made up of four

subunits

 Each subunit contains one iron atom

 Myoglobin

 Myoglobin is present in muscles

 It is a monomer having one iron atom

 Cytochromes

 Cytochromes are present in respiratory chain,

and support tissue respiration

 Cytochrome P-450 and cytochrome b5 are

components of microsomal hydroxylase system
 Ferritin

 Ferritin is present in liver, spleen, bone marrow,

brain, kidneys, intestine, placenta etc

 It is one of the storage forms of iron

 The protein portion is known as apoferritin

 Apoferritin combines with iron to form ferritin

 The first step in the synthesis of ferritin is the
formation of apoferritin induced by the entry of
ferrous iron in the cell

 This is followed by oxidation of ferrous iron to

the ferric form

 Ferric iron forms ferric hydrophosphate

micelles, which enter the protein shell to form
ferritin
Ferritin

Apo-ferritin
 Apoferritin is made up of 24 identical subunits,
each having a molecular weight of 22,000 to
24,000

 The subunits are arranged at the vertices of a

pentagonal dodecahedron with a hollow space in
the centre
 Ferric hydrophosphate micelles are present in
this space

 When fully saturated, a molecule of ferritin

contains 5,000 atoms of iron, and has a molecular
weight of 900,000
 Haemosiderin

 Haemosiderin is a granular iron-rich protein

 It is insoluble in water unlike ferritin

 The exact structure of haemosiderin is not

known

 It has been shown that iron is first stored in the

body in the form of ferritin
 As the iron stores increase, the older ferritin
molecules are aggregated to form haemosiderin

 Some of the protein is degraded in this process

 Therefore, the percentage of iron in

haemosiderin is higher as compared to that in
ferritin

 Normally, about two thirds of the stored iron is in

the form of ferritin and one third in the form of
haemosiderin
 Transferrin

 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 is a b1-globulin with a molecular
weight of about 90,000

 It is made up of two non-identical subunits

 One molecule of transferrin can transport two

ferric atoms
 Transferrin carries iron to and from various
tissues through circulation

 There are specific receptors for transferrin on the

cell membranes of the cells requiring iron e.g. red
cell precursors

 Transferrin-iron complex binds to these receptors

 Transferrin
Iron

Transferrin
receptor

Cell
membrane
 The binding produces a conformational change
in the transferrin molecule as a result of which the
iron is released

 The free transferrin molecule is then displaced

from the receptor by molecules carrying iron
 The concentration of transferrin in plasma is
200-400 mg/dl

 This amount of transferrin is capable of carrying

250-400 mg of iron per dl of plasma

 This is known as the total iron binding capacity

of plasma
 Normal plasma iron level is 50-175 µg/dl

 This means that the iron binding capacity of

plasma is only about 30% saturated in healthy
subjects
 Iron-containing enzymes

 Several enzymes require iron for their catalytic

activity

 In some cases, iron forms an integral part of the

enzyme molecules

 In others, presence of iron is required for the

catalytic activity of the enzymes
 The iron-containing enzymes are mostly
concerned with biological oxidation

 Examples of such enzymes are catalase,

peroxidase, aconitase, succinate dehydro- genase,
xanthine oxidase etc
Functions

Transport of oxygen

Oxidative reactions

Tissue respiration

EMB-RCG
 Transport of oxygen

 The most important function of iron is to

transport oxygen in the body in the form of
haemoglobin

 A similar function is performed in muscles by

myoglobin
 Oxidative reactions

 Iron is a component of various oxidoreductase

enzymes

 As such, it plays a role in a number of oxidative

reactions
 Tissue respiration

 As a component of cytochromes in the

respiratory chain, iron is involved in tissue
respiration

 It is the iron component of the cytochromes that

accepts and donates electrons
 Iron balance

Iron status depends upon the relative rates of iron

absorption and iron excretion

Iron absorption is the major mechanism for

maintaining normal iron balance

EMB-RCG
Iron metabolism is said to occur within a closed
system in the body

There is hardly any exchange of iron between

man and his environment

The iron present in the body is continuously

reutilized

Only a minute amount of iron is lost everyday

from the body in the form of exfoliated cells

EMB-RCG
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 skin

along with the exfoliated cells

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

day

EMB-RCG
In premenopausal women, there are two
additional routes of iron loss

About 20-25 mg of iron is lost with menstrual

blood in each cycle

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

iron

EMB-RCG
0.6 mg a day in the first trimester

2.8 mg a day in the second trimester

4.0 mg a day in the third trimester

EMB-RCG
 Iron loss is balanced by intestinal absorption

 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
 Absorption is more when:
• Body iron stores are low
• Erythropoietic activity is high
• Saturation of plasma transferrin is low
• Iron is ingested in ferrous form
 Iron absorption is increased by the presence of :
• Ascorbic acid
• Succinic acid
• Histidine
• Cysteine

 Iron absorption is decreased by the presence of :

• Phytates
• Phosphates
Iron can be absorbed from all segments of the
small intestine but presence and normal
functioning of stomach are also essential

Patients with achlorhydria and those who have

undergone gastrectomy absorb less iron as
compared to normal persons

Gastric enzymes and hydrochloric acid release

iron from iron-containing compounds and reduce
ferric iron to the ferrous form

EMB-RCG
It is believed that ferritin content of mucosal cells
of the intestine regulates the absorption of iron

These cells are formed in the crypts of

Leiberkuhn

They gradually reach the tip of the villi and are

shed off into the intestinal lumen

Their average life-span is three days

EMB-RCG
The function of ferritin in these cells is to block the
absorption of iron

Those cells which are formed during a period of

iron overload are rich in ferritin

These cells will absorb little iron during their life-

span

Moreover, when these are shed off, their iron

content will also be lost in faeces

EMB-RCG
Conversely, the cells formed during a period of
iron deficiency are poor in ferritin

These cells absorb more iron and transfer it into

the plasma

EMB-RCG
 Requirement

Only a small proportion of the dietary iron is

normally absorbed

Therefore, much larger amounts have to be

provided in diet than the actual requirement

EMB-RCG
 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
 Dietary sources

 Liver, heart, kidney, spleen, meat, fish and eggs

are good sources of iron

 The vegetable sources include whole wheat,

figs, dates, nuts, beans, spinach, molasses etc
 Much greater proportion of iron is absorbed from
animal foods than from vegetable foods

 On a mixed diet, healthy subjects absorb

5-10% of the dietary iron
 Iron deficiency

 Iron deficiency is widespread both in poor and in

affluent countries

 Iron deficiency is the commonest cause of

anaemia throughout the world
Deficiency can be caused by :

Inadequate intake

Malabsorption

Blood loss

EMB-RCG
Inadequate intake is likely when
requirement is high e.g. in:

Infancy

Adolescence

Pregnancy

EMB-RCG
Malabsorption can be due to:

Steatorrhoea

Coeliac disease

Gastrectomy

EMB-RCG
Persistent blood loss can occur from:

Genital tract

Gastrointestinal tract

Hookworm infestation

EMB-RCG
When iron deficiency develops, the earliest
change is a depletion of body iron stores

Other changes follow progressively

Plasma transferrin saturation is decreased

Plasma iron is decreased

EMB-RCG
A microcytic, hypochromic anaemia develops

Poikilocytosis becomes evident

Hemoglobin level falls

EMB-RCG
Severe and prolonged deficiency leads to :

Koilonychia

Angular stomatitis

Glossitis

Pharyngeal and oesophageal webs

Atrophic gastritis

Partial villus atrophy

EMB-RCG
 Iron overload

 Iron overload is much less common than iron

deficiency

 Two types of iron overload syndromes are known:

• Haemosiderosis
• Haemochromatosis
 Haemosiderosis

 Excess iron is deposited in reticulo-endothelial

cells

 There is no tissue damage

 Excess iron enters the body through the

parenteral route

 This can be due to repeated blood transfusions

e.g. in thalassaemia
 Haemochromatosis

 Excess iron enters the body through the

alimentary route

 It gets deposited in parenchymal cells and

causes tissue damage

 It may be primary or secondary

 Primary (genetic) haemochromatosis is far more

common
 The gene responsible for primary haemo-
chromatosis has not been identified

 The genetic defect leads to excessive intestinal

absorption of iron

 Excess iron is deposited in liver, heart, pancreas

and other endocrine glands, skin etc

 The condition is also known as bronzed diabetes

 Clinical abnormalities in bronzed diabetes are:
• Hepatomegaly
• Cardiomegaly
• Congestive heart failure
• Hypogonadism
• Diabetes mellitus
• Bronze-coloured pigmentation of skin
 Serum iron, ferritin and per cent saturation of
iron-binding capacity are increased in haemo-
chromatosis

 Phlebotomy and iron-chelating agents e.g.

desferrioxamine are used to remove excess iron
 Secondary haemochromatosis may occur in
alcoholic liver disease in which iron deposition is
usually confined to hepatic tissue

 South African Bantus are known to develop

haemochromatosis due to excessive ingestion of
iron present in an alcoholic beverage brewed in
iron vessels
 Iodine

 Total iodine in an average adult is 45-50 mg

 About 10-15 mg is present in the thyroid gland

 Muscles contain about 25 mg

 About 5 mg is present in skin, 3 mg in the

skeleton and 2 mg in liver
 Functions

 The only known function of iodine is in the

synthesis of thyroid hormones

 The thyroid gland synthesizes tri-iodo-

thyronine(T3) and tetra-iodo-thyronine(T4)

 These are synthesized from iodine and tyrosine

residues of thyroglobulin
 The thyroid gland:
• Actively takes up iodide ions from plasma
• Oxidises them to iodine
• Incorporates iodine into tyrosine residues of
thyroglobulin
• The products are mono-iodo-tyrosine (MIT)
and di-iodo-tyrosine (DIT)
 Two DIT residues combine to form thyroxine
(T4)

 One MIT and one DIT residues combine to

form tri-iodo-thyronine (T3)
 Absorption

 Iodine is absorbed from all parts of the

alimentary tract, particularly from the small intestine

 Iodine and iodate are converted into iodide prior

to absorption

 Other mucous membranes and skin can also

absorb iodine
 The iodide absorbed from the alimentary tract
and elsewhere enters the circulation

 About one third is taken up by the thyroid

gland

 The remainder is excreted, mainly by the

kidneys

 Small amounts of iodide are excreted in saliva,

bile, milk, sweat and expired air
 Plasma iodine level is 4-10 mg/dl

 Only 10% of it is present in the form of

inorganic iodide

 Organic iodine is present mostly in the form of

thyroid hormones

 Thyroid hormones are bound to some proteins

(protein bound iodine)
 Daily requirement

Age Requirement
Infants 40-50 µg/day
Children 70-120 µg/day
Adults 150 µg/day
 Dietary sources

 Iodine is present in water and soil

 Foods, both animal and plant, obtain iodine from

water and soil

 Iodine content of foodstuffs depends upon the

iodine content of water and soil
 Sea water is rich in iodine

 Therefore, sea foods, e.g. fish, oysters, lobsters

etc, are the best sources of iodine

 As we go away from the sea, the iodine

content of water and soil, and hence of the
foodstuffs, decreases
 Iodine deficiency

 Iodine deficiency is common in certain areas of

the world

 These areas constitute the so-called goitre belt

 Sub-Himalayan region of India is a part of this

belt as the iodine content of soil and water is poor in
this region
 A high prevalence of non-toxic goitre (endemic
goitre) is seen in this region

 Thyroid gland becomes hypertrophic in order

to produce enough hormones from available iodine

 A severe deficiency can produce hypothyroidism

 Endemic goitre can be prevented by providing

iodized table salt in the goitre belt
 Iodized salt is prepared by mixing potassium
iodate with common salt in the proportion of
1:10,000-20,000

 Injection of iodized poppy seed oil has also been

successfully used in some countries

 One dose is sufficient for 2-4 years

 Copper

 About 60-100 mg of copper is present in an

average adult

 Relatively large amounts of copper are present

in muscles (30-50 mg), bones (12-20 mg) and liver
(9-15 mg)
 Plasma copper level is 100-200 mg/dl

 Nearly 90% of the plasma copper is tightly

bound to ceruloplasmin

 The rest is loosely attached to albumin

 Albumin is the major carrier of copper as it can
easily release copper

 Many tissues contain minute amounts of copper

in the form of copper-containing enzymes
 Functions

 Copper performs its physiological functions in the

form of copper-containing enzymes

 These include cytochrome oxidase, superoxide

dismutase, monoamine oxidase, tyrosinase,
dopamine hydroxylase etc

 Ceruloplasmin also functions as ferroxidase

which oxidises ferrous iron to the ferric form
 Copper is also required for:
• Synthesis of haemoglobin
• Formation of bones
• Maintenance of myelin sheath of nerves
 Absorption

 About one third of the dietary copper is normally

absorbed, mainly from small intestine

 Copper-binding P-type ATPase, an enzyme

present in intestinal mucosa (and many other cells)
transfers copper into portal circulation
 Albumin carries it to liver

 A different copper-binding P-type ATPase

present in liver incorporates copper into apo-
ceruloplasmin
 Daily requirement

 Adults require about 2.5 mg of copper daily

 Infants and children require about 0.05 mg/kg of

body weight
Sources

Liver

Kidney

Meat

Nuts

Legumes

Raisins
 Disorders of copper metabolism

 Wilson’s disease (hepatolenticular

degeneration) is an autosomal recessive disease
in which the synthesis of ceruloplasmin is impaired

 Large amounts of copper are deposited in liver,

basal ganglia and around cornea

 Serum copper and ceruloplasmin levels are low

 Urinary excretion of copper is increased

 Recent work has shown that copper-binding P-

type ATPase is congenitally deficient in liver in this
disease

 This impairs the incorporation of copper into

apo-ceruloplasmin and its biliary excretion leading
to copper toxicity
 Another inherited disorder of copper metabolism
is Menkes’ disease which is an X-linked recessive
disease

 In this disease, copper-binding P-type ATPase is

deficient in intestinal mucosa and most other
tissues except liver

 Copper accumulates in intestinal mucosa but

can not be released into circulation
 This leads to a deficiency of copper in tissues

 The deficiency causes cerebral degeneration,

hypochromic microcytic anaemia and steely or
kinky hair
 Serum copper and ceruloplasmin levels are
elevated in:
• Pregnancy
• Infections
• Leukaemia
• Collagen diseases
• Myocardial infarction
• Cirrhosis of liver
 Zinc

 The total amount of zinc in an average adult is

1.3-2.1 gm

 Its tissue distribution is very wide

 Prostate, liver, kidneys, muscles, heart, skin,

bones and teeth are particularly rich in zinc
 Plasma zinc level is 50-150 µg/dl

 Blood cells, erythrocytes and leukocytes, have a

higher concentration of zinc than plasma
 Functions

 Zinc is essential for normal growth and sexual

development

 It is required for the synthesis of nucleic acids,

which is essential for cell division and growth

 In the form of zinc fingers, it is a constituent of

some proteins which regulate transcription
 Many enzymes require zinc for their catalytic
activity

 These include carbonic anhydrase, carboxy-

peptidase, lactate dehydrogenase, malate
dehydrogenase, glutamate dehydrogenase,
alcohol dehydrogenase, alkaline phosphatase etc
 Zinc is present in the b-cells of the islets of
Langerhans

 It is required for the storage and release of

insulin
 Absorption

 Zinc is absorbed from the small intestine

 Copper, cadmium and calcium interfere with the

absorption of zinc

 Phytates also retard zinc absorption by forming

an insoluble complex with zinc
 Daily requirement

Age and sex Requirement

Infants 5 mg/day
Children 10 mg/day
Adult men 15 mg/day
Adult women 12 mg/day
Pregnant women 15 mg/day
Lactating women 20 mg/day
 Dietary sources

 Zinc is widely distributed in foodstuffs

 Liver, kidney, meat, fish, eggs, milk, yeast and

whole grain cereals are good sources of zinc
 Zinc deficiency

 A dietary deficiency of zinc may occur in

vegetarians taking refined wheat flour as their staple
diet

 It can also occur in acrodermatitis

enteropathica
 It causes retardation of growth, dwarfism,
delayed puberty and hypogonadism

 A milder deficiency may cause poor wound

healing and impaired perception of taste
 Cobalt

 About one mg of cobalt is present in an average

adult

 It is distributed chiefly in liver, kidneys and bones

 It is present almost entirely as a constituent of

vitamin B12
 Inorganic cobalt is not known to perform any
biological function in human beings

 It functions solely as a component of vitamin B12

 It must be provided in the diet as vitamin B12

 Inorganic cobalt is not absorbed from the

alimentary tract

 Injected cobalt is rapidly excreted in urine

 Manganese

 About 12-20 mg of manganese is present in an

average adult

 Liver, pancreas and kidneys contain relatively

more manganese than other tissues
 Manganese is present mainly in the
mitochondria and nuclei of the cells

 Manganese is absorbed from the small intestine

 Less than 5% of the ingested manganese is

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 e.g.
• Superoxide dismutase
• Arginase
• Acetylcholine esterase
• RNA polymerase
• Carboxylases
• Glycosyl transferases
 The daily manganese requirement is believed to
be 2-5 mg

 Whole-grain cereals, legumes, nuts, green

vegetables and fruits are good sources of
manganese
 Molybdenum

 Molybdenum is present in very small amounts

in the human body, principally in liver and kidneys

 It is a component of xanthine oxidase, aldehyde

oxidase and sulphite oxidase

 Sulphite oxidase converts sulphite and sulphur

dioxide into sulphate
 The exact requirement for molybdenum is
unknown

 An average diet provides 75-100 µg of

molybdenum a day

 Molybdenum deficiency is unknown in human

being

 Excessive intake of molybdenum may cause

copper deficiency
 Chromium

 The total amount of chromium in an average

adult is about 6 mg

 It is widely distributed in the body

 Chromium is a constituent of glucose tolerance

factor (GTF) which binds to insulin and
potentiates its actions
 A relationship between chromium deficiency and
glucose intolerance has been shown

 The absorption of chromium is less than 1%

 Stainless steel utensils contain chromium which

can be absorbed

 Chromium requirement is about 0.2 mg/day

 Excess chromium can be toxic

 Selenium

 Selenium is present in human body in minute

amounts

 About 6 mg is present in an average adult

 It is widely distributed in the body

 Kidneys, liver, muscles, pancreas, pituitary and

skin contain relatively more selenium
 The role of selenium in the nutrition of animals
has been known for sometime

 It is involved in normal growth, reproductive

functions and prevents hepatic necrosis and
muscle dystrophy in several animal species

 Its exact role in human beings is still being

investigated
 It may be involved in the synthesis of coenzyme
Q

 It is believed to play a role in immune response

 It is a component of some proteins in the form of

selenocysteine
 The most definitive role of selenium,
discovered so far, is in the prevention of
peroxidation of lipids and other compounds

 Hydrogen peroxide, formed in the tissues by

the action of aerobic dehydrogenases and
superoxide dismutase, is a toxic compound
 It is detoxified by reduced glutathione

2 G – SH + H2O2 GS – SG + 2 H2O
Reduced Oxidised
glutathione glutathione

 This reaction is catalysed by glutathione

peroxidase
 Selenium is a constituent of glutathione
peroxidase

 Glutathione peroxidase can also detoxify fatty

acid hydroperoxides (R-OOH) formed by the action
of hydrogen peroxide on fatty acids
 Thus, selenium acts as an anti-oxidant

 It protects the tissues against the potentially

toxic effects of hydrogen peroxide

 Vitamin E also does the same but by a different

mechanism
 The selenium requirement is about:
• 70 µg/day in adult men
• 55 µg/day in adult women
 Fluorine

 About 2.6 gm of fluorine is normally present in

the human body

 More than 95% of it is present in bones and

teeth

 Fluorine is ingested in the form of fluorides

 It is readily absorbed from the gut and enters
the extracellular fluids

 Fluoride makes the bones resistant to osteo-

porosis in later life

 It makes the teeth resistant to dental caries

 Certain bacteria, normally present in the oral
cavity, act on dietary carbohydrates and convert
them into lactic acid

 Lactic acid corrodes the enamel of the teeth and

produces cavities (dental caries)

 Fluoride hardens the enamel, and makes it

resistant to attack by lactic acid
 Drinking water is the main source of fluoride

 Seafood, cheese and tea may provide small

amounts but other foods are generally poor in
fluoride

 The fluoride intake generally depends upon the

fluoride content of water
 In India, where water intake is relatively high,
a fluoride content of 0.5-0.8 parts per million
(ppm) in water will provide sufficient fluoride

 If the fluoride content is less than this, dental

caries may become a public health problem

 In such areas, fluoride must be added to the

drinking water (fluoridation) to raise its fluoride
concentration to 0.5-0.8 ppm
 Fluoride is potentially toxic

 Excessive intake causes fluorosis which may be:

• Dental fluorosis
• Skeletal fluorosis
 Fluorosis occurs when fluoride content of water
exceeds 1.2 ppm or the daily fluoride intake
exceeds 3 mg

 In mild cases, only the teeth are affected (dental

fluorosis)

 The teeth become mottled and corroded

 In severe cases, the bones are also affected
(skeletal fluorosis)

 The bones of the vertebral column, pelvis

and limbs become deformed

 Tendons and ligaments are calcified

 Fluorosis occurs in those geographical areas
where the fluoride content of water is high

 Defluoridation of water is recommended in such

areas to prevent fluorosis