Mineral Metabolism

MINERAL METABOLISM
Mr.Tapeshwar Yadav
(Lecturer)
B.M.L.T, D.N.H.E
M.Sc. Medical Biochemistry

Minerals
 Minerals are essential for normal growth and
maintenance of the body.
 Major elements : Requirement >100 mg /day
Calcium Chloride
Magnesium Sulphur
Phosphorous Fluoride
Sodium
Potassium

Contd….
 Trace Elements : Requirement <100mg/day
Iron Zinc
Iodine Molybdenum
Copper Selenium
Manganese

Contd….
 Some are necessary for the body but their exact
functions are not known.
Ex.: Chromium, Nickel, Bromide, Lithium,
Barium
 Non-Essentials : seen in tissues. Contaminants in
food stuffs.
Ex.: Rubedium, Silver, Gold, Bismuth
 Toxic : should be avoided.
Ex.: Aluminium, Lead, Cadmium, Mercury

CALCIUM (Ca)
Total Calcium in human body: 1 – 1.5 Kg
In Bones – 99 %
In extra cellular fluid – 1 %
Sources :
- Milk (Cow’s Milk – 100mg/100ml)
- Egg, Fish, Vegetables - moderate
- Cereals (wheat, rice) - poor source

Daily Requirement
Adults : 500 mg/day
Children : 1200 mg/day
Pregnancy and Lactation : 1500 mg/day
>50 yrs. : 1500 mg/day
+20µg Vit.D
(to prevent osteoporosis)

Absorption
 1st
and 2nd
part of duodenum
 Against concentration gradient and
requires energy
 Requires carrier protein

Factors promoting Ca absorption
Vitamin – D (calcitriol)
synthesis of carrier protein calbindin – facilitates
absorption
Parathyroid Hormone – ↑ Ca transport from
intestinal cells
Acidity – favors Ca absorption
Amino acids – Lysine and Arginine

Factors Inhibiting Ca absorption
Phytates and oxalates - form insoluble calcium
oxalates
High dietary phosphates - precipitate as calcium
phosphate
High pH - (alkaline)
High dietary fiber
Mal absorption syndrome - Fatty acids not absorbed
and form insoluble calcium salts of fatty acid

Functions
1. Bones & Teeth :
Formation of bone & teeth.
Bones are reservoir for Ca in the body.
Osteoblasts → bone deposition
Osteoclasts → demineralization.

2. Muscle Contraction :
Ca mediates excitation & contraction of
muscle fibers.
Ca interacts with Troponin-C to trigger
muscle contraction.
Ca activates ATPase, ↑ interaction between
actin and myosin.

3. Nerve Conduction :
Transmission of nerve impulses from pre-
synaptic to post-synaptic region.
4. Secretion of hormones :
Mediates the secretion of Insulin, PTH,
Calcitonin, Vasopressin etc.

5. Second Messenger :
Ca & cyclic AMP are 2nd
messengers of
different hormones. Eg: Glucogan
6. Membrane integrity & Permeability :
Influences transport of number of
substances across the membranous barrier.

7. Blood Coagulation :
Factor IV in blood coagulation cascade.
prothrombin → Thrombin
8. Action on Heart :
Ca prolongs Systole.
↑ Ca concentration → ↑ myocardial
contractility

The Calcium-Binding Region of Prothrombin
Prothrombin binds calcium ions with the modified
amino acid g-carboxyglutamate (red).

9. Activation of Enzymes :
Calmodulin – Ca binding regulatory
protein. Binds with 4 Ca ions and leads
to activation of enzymes.

Calmodulin contains four similar units in a single
polypeptide chain shown in red, yellow, blue, and
orange. Each unit binds a calcium ion (shown in green).

Plasma Calcium
Normal Plasma / Serum Calcium : 9 – 11 mg / dl
Ionized Calcium : 5 mg/dl
Protein bound Calcium : 4 – 5 mg/dl
Complexed with phosphate/citrate/ bicarbonate :
about 1 mg/dl

Homeostasis of Ca
The major factors that regulate the
plasma Calcium
• Calcitriol
• Parathyroid hormone
• Calcitonin

Calcitriol
• ↑ intestinal absorption of Ca.
• Stimulates Ca uptake by osteoblasts and
promotes Calcification.

P T H
Elevates serum Ca
• Demineralization of bone (Osteoclasts)
• Increases Ca reabsorption by renal tubules
• Increases intestinal absorption of Ca by
promoting synthesis of Calcitriol

Calcitonin
secreted by Para follicular cells of Thyroid gland
Lowers the serum Ca levels
• Calcification of bone (by osteoblasts)
• Increases the excretion of Ca into urine
Calcitonin & PTH are directly antagonistic

Calcitriol PTH Calcitonin
Blood calcium ↑ ↑ ↓
Main action Absorption
from gut
Deminerali
-zation
Oppose
demineraliza
-tion

Disorders of Calcium Metabolism
Hypercalcemia : > 11 mg/dl
causes:
Hyperparathyroidism - Parathyroid adenoma
ectopic parathyroid
secreting tumor
 Multiple myeloma
 Paget’s disease
 Metastatic carcinoma of bone.

Hypocalcemia
TETANY
Ca < 8.5 mg/dl → mild tremors
< 7.5 mg/dl → typical Tetany
Causes :
Accidental removal of parathyroid glands
Autoimmune disease

Symptoms :
• Neuromuscular irritability
• Carpopedal spasms
• Laryngismus → stridor (noisy breathing)
laryngeal spasms may lead to death.
Signs : Chovstek’s sign +
Trousseau’s sign +
↑ Q-T interval in ECG

Chovstek’s sign
• A twitch of the facial
muscles following
gentle tapping over the
facial nerve in front of
the ear that indicates
hyperirritability of the
facial nerve

Trousseau’s sign
• A test for latent tetany in which carpal
spasm is induced by inflating a
sphygmomanometer cuff on the upper arm
to a pressure exceeding systolic blood
pressure for 3 minutes.

“Centre for the Learning’’

• Total body iron content : 3 - 5 gm
• Iron is present in almost all cells
• Heme containing proteins: Hb, myoglobin,
cytochromes, cytochrome oxidase, catalase,
peroxidase, xanthine oxidase & Trp pyrrolase

• 75% of total Fe is in Hb & 5% in myoglobin
• Non-heme iron containing proteins : ferritin,
transferrin, hemosiderin, lactoferin (milk) &
neutrophils

 Tissue Respiration :
Iron can change readily between Ferrous and
Ferric states and function in electron transfer
reactions.
Cytochromes
NADH dehydrogenase
Succinate dehydrogenase

 Transport of gases :
 Able to bind with molecular O2and CO2.
 The main function is to coordinate the O2
molecule into heme of hemoglobin, so that it can
be transported from the lungs to the tissues.

 Oxidative Reactions :
Component of various oxidoreductase enzymes
-vital role in oxidative reactions.

 Immune Response :
Required for effective activity of lysosomal
enzyme peroxidase – helps in phagocytic and
bactericidal activity of neutrophils.

 Indian diet contain >10 – 20 mg of Iron.
only about 10% of it is absorbed.
 1 mg is eliminated each day from human
body by shredding of skin
epithelial cells & cells lining urinary
tract & small extent in urine + sweat.

 20-40 mg - blood loss in each
menstrual cycle.
 ↑ daily demand to 3-4 mg in pregnant &
lactating women.
 900 mg – diversion of Iron to foetus in
pregnancy.
blood loss during
delivery
subsequent breast
feeding

Children : 10 mg/day
AdultsAdults
Males : 10-12 mg/day
Women
Premenopausal : 18 mg/day
Postmenopausal : 10 mg / day
Pregnant & Lactating : 40 mg/day

 Good sources: Leafy vegetables (20mg/100g),
pulses (10mg/100g), cereals (5mg/100g),
liver (5mg/100g), meat (2mg/100g), fish,
dried fruits, jaggery and iron cookware
 Poor sources: Milk (0.1 mg/100 ml), wheat,
polished rice

 Ferric ions are reduced with the help of gastric
HCl, ascorbic acid, cys. and -SH groups of pro.
--------- favors absorption.
 Ca, Cu, Zn, Pb ------------- inhibit absorption.
 Phytates (in cereals), oxalates (leafy veg) &
phosphates in the diet reduce absorption by
forming insoluble iron salts.
 Marginal ↓ by tea & eggs.

Mucosal block theory
 Absorbed by upper part of duodenum
 Homeostasis is maintained at the level
of absorption
 Iron stores depleted -
absorption ↑
 Iron stores adequate -
absorption ↓
 Only Fe++
(ferrous) form is
absorbed and not Fe+++
(ferric)

 Ferrous Iron binds to mucosal cell protein
called Divalent Metal Transporter - 1 (DMT-1).
 This bound Iron is then transported into the
mucosal cell.
 Unabsorbed Iron is excreted.

Lumen of GIT Mucosal cells of GIT Plasma
Tissues
Food Fe Apoferritin Apotransferrin
HCl
Organic acids Ferritin Transferrin
(Fe+++
)
Fe+++
Fe+++
Ferro- Fe+++
Ascorbic acid reductase
Cysteine Ferroxidase Fe++ Ceruloplasmin
or Ferroxidase II
Fe++
Fe++
Fe++
Iron absorption and transport
Liver
Ferritin
hemosideri
n
Bone marrow (Hb)
Muscle (Mb)
Other tissues

 Iron oxidized to ferric state.
complexed with apoferritin to form Ferritin.
 Ferric Iron is released, reduced to Ferrous state
crosses the cell membrane.

 Reoxidized to Ferric state by Ceruloplasmin
 Ferric Iron bound with Transferrin and
transported to tissues.

 One-way element (very little of it is excreted)
 Almost no iron is excreted through urine
 Any type of bleeding will cause the loss
 Normal level in plasma -------- 50 - 175 µg/dl

 Iron deficiency anemiaIron deficiency anemia is the most
common nutritional deficiency diseases
 Characterized by microcytic hypochromicmicrocytic hypochromic
anemiaanemia (blood Hb <12 g/dl)

Clinical Manifestations:
 Anemia, Apathy
 Achlorhydria
 Impaired attention, Irritability, Lowered memory
 Koilonychia (spoon nails)

 Hookworm infection
 Nephrosis
 Repeated pregnancy
 Lack of absorption
 Nutritional deficiency of Fe
 Chronic blood loss (piles, peptic ulcer, uterine
hemorrhage)

HEMOSIDEROSIS --------- uncommon
 Occurs in persons receiving repeated blood
transfusion (in hemophilia, hemolytic anemia).
 Common in Bantu tribe, because of staple diet,
corn, is low in phosphates, and their habit of
cooking foods in iron vessels.

It is manifested when total body iron is >25-30
gm, where hemosiderin is deposited in almost all
tissues.

 Primary Hemochromatosis :
- genetic disorder – excessive storage of
Iron in tissues → tissue damage.
 Secondary Hemochromatosis :
- repeated blood transfusions
- excessive oral intake of Iron
eg. as in African Bantu tribes

Deposition of iron
 Liver cell death ------ cirrhosiscirrhosis
 Pancreatic cell death -------- diabetesdiabetes
 Deposits under the skin cause yellow-brown
discoloration ---------- hemochromatosishemochromatosis
 The triad of cirrhosis, diabetes and
hemochromatosis ------- bronze diabetesbronze diabetes

 The total body phosphate – 1 kg
80 % - Bone &Teeth
10 % - Muscles
 Mainly Intracellular ion – seen in all cells.

 Formation of bone & teeth
 Production of high energy phosphates:
ATP CTP GTP
creatine phosphate
 Synthesis of nucleoside co-enzymes:
NAD+
and NADP+
 DNA and RNA synthesis:
Phosho-diester linkages–backbone of structure

 Formation of phosphate esters:
Glucose 6-phosphate, phospholipids
 Formation of phosphoprotein: Casein
 Activation of enzymes by phophorylation
 Phosphate buffer system of blood:
maintain the pH of blood at 7.4.

 500 mg/day
 Milk - good source
cereals
Nuts moderate source
Meat
 Calcitriol increases phosphate absorption

 Normal adults - 3 – 4 mg/dl
 Children - 5 – 6 mg/dl
 Whole blood phosphate – 40 mg/dl
 Decrease in phosphate levels:
Hyperparathyroidism
Rickets

“To be good & to do good that is the whole of religion”

Chief cation of Extracellular fluid.
Total body Sodium – 4000 mEq
50 % in bones
40 % in extracellular fluid
10 % in soft tissues

Biochemical FunctionsBiochemical Functions
Sodium (as sodium bicarbonate) regulates
the body acid base balance.
Sodium regulates ECF volume:
 Sodium pump is operating in all cells, so as
to keep Sodium extracellular.
 This mechanism is ATP dependent.

Required for maintenance of osmotic
pressure and fluid balance.
Necessary for normal muscle irritability
and cell permeability.

Daily requirementDaily requirement
Normal diet contains 5 – 10 gm of sodium
mainly as sodium chloride
Sources :
Common salt used in cooking medium
Bread whole grains
Nuts leafy vegetables
Eggs Milk

AbsorptionAbsorption
Readily absorbed in the GI tract.
very little < 2 % is found in faeces.
In Diarrhea – large quantities of sodium
is lost in faeces.

ExcretionExcretion
Kidney – major route of sodium
excretion
800 gm/day of Na filtered in glomuruli
99 % - reabsorbed by proximal convoluted
tubule.
↑ reabsorption in distal tubules controlled
by aldosterone.

In edema – water & sodium content of
the body increase.
Diuretic drugs – excrete Na also along
with water.

NormalValuesNormalValues
In plasma - 136 – 145 mEq/L
In cells - 35 mEq/L
Mineralocorticoids influence Na metabolism
in adrenocortical insufficiency
↓ plasma Na
↑ urinary excretion of Na

HypernatremiaHypernatremia
Cushing’s disease
Prolonged cortisone therapy
In dehydration – water predominantly lost
the blood volume decreased with
apparent conc. of sodium↑

HyponatremiaHyponatremia
Vomiting
Diarrhea
Burns
Addison’s disease (adrenal insufficiency)
In severe sweating, Na is lost considerably
- muscle cramps & headache.

Biochemical estimationBiochemical estimation
Flame photometer
Ion selective electrodes

Principal intraracellular cation.
Total body Potassium – 3500 mEq
75 % in skeletal muscle
Required for regulation of acid base balance
and water balance in cells.
Maintains intracellular osmotic pressure.
Required for transmission of nerve impulse.

Enzyme – Pyruvate kinase (of glycolysis) depend on
K+
for optimal activity.
Adequate intracellular concentration of K+
is necessary
for proper biosynthesis of proteins by ribosomes.
Extracellular K+
influences cardiac muscle
activity.

Dietary requirement
3 – 4 g / day
Sources :
Banana Potato
Orange Beans
Pineapple Chicken
Liver
Tender coconut water – rich source

Absorption & excretion
Absorption: From GI tract – very efficient
(90%)
In diarrhea – good proportion of K+
is lost in feces
Excretion : Through urine
Aldosterone excretion of potassium.↑

Normal values
In plasma : 3.4 – 5.0 mEq/L
In whole blood : 50 mEq/L
Either high or low concentrations are
dangerous since K+
affects contractility of
cardiac muscle

Hypokalemia
Over activity of Adrenal cortex (Cushing’s
syndrome)
Prolonged cortisone therapy
Prolonged diarrhea & vomiting
Diuretics used for CCF may cause K+
excretion
S/S: irritability, muscular weakness, tachycardia,
cardiomegaly & cardiac arrest
ECG - flattened waves with T ↓

Hyperkalemia
Renal failure
Adrenocortical insufficiency (Addison’s disease)
Diabetic coma
S/S : depression of CNS
mental confusion
numbness
bradycardia - cardiac arrest
ECG - T ↑

Prevents dental caries
Increases hardness of bones and teeth
Sources: drinking water
Requirements
Children : 0.5-2.5 mg/day
Adults : 2.0-5.0 mg/day
Safe limit of fluoride : 1 ppm (parts per million)
1 ppm: 1 gm of F in million gm of water, which
is equal to 1 mg per 1000ml

Dental caries: < 0.5 ppm
Dental fluorosis: > 2 ppm
In children; mottling of enamel &
discoloration of teeth.
In adults; chronic intestinal upset, loss of
weight, loss of appetite & gastroenteritis
Skeletal fluorosis: >20 ppm; toxic
Osteoporosis & osteosclerosis, with brittle
bones

 Ligaments of spine & collagen of bones get
calcified
Genu valgum: advanced cases of skeletal
fluorosis (stiff joints)
Plasma: normal value : 4 µg/dl
fluorosis : 50 µg/dl

Iodine
• Total body iodine : 25-30 mg (80% in
thyroid gland)
Formation of thyroid hormones (T3 & T4)
Requirements:
Children : 40-120 µg/day
Adults : 100-150 µg/day
Pregnant women : 175 µg/day

Commercial source: seaweeds
Other sources: drinking water, vegetables,
fruits, iodized salt
Absorption: small intestine
only 30% of iodine in food is absorbed
GoiterogenousGoiterogenous substancessubstances prevent absorption of
iodine
Eg: i, Cabbage & tapioca contain thiocyanatethiocyanate,
which inhibits iodine uptake by thyroid
ii, Mustard seed contains thioureathiourea, which
inhibits iodination of thyroglobulin

Storage: iodothyroglobulin (glycoprotein)
Excretion: mainly through urine and also
through bile, saliva and skin
Plasma: 4-10 µg/dl
Deficiency:
Children : cretinism
Adults : goiter, hypothyroidism, myxedema

Zinc
Total body Zn: 2 gm (99% is intracellular)
60% in skeletal muscle
30% in bones
Prostate gland contains 100 µg/g & liver 50
µg/g
Sources: grains, beans, nuts, cheese, eggs, milk,
meat & shell fish

Absorption: duodenum
Cu, Ca, Cd, Fe & phytate interfere absorption.
Storage: in liver with a specific protein,
metallothionine.

Biochemical functions
 Cofactor for more than 300 enzymes
eg: carboxy peptidase, carbonic anhydrase,
ALP, LDH, ADH, superoxide dismutase &
glutamate dehydrogenase.
 Participate in the metabolism of
carbohydrates, lipids, proteins & nucleic
acids.

Stabilizes insulin, when stored in β- cells of
pancreas.
Promotes the synthesis of retinol binding
protein.
GustenGusten, Zn containing protein in saliva, is
important for taste sensation.
Role in growth, reproduction & wound
healing.

Requirement:
Children : 5-10 mg/day
Adults : 10-15 mg/day
Pregnancy & lactation : 15-20 mg/day
Deficiency:
Hypogonadism
Growth failure
Impaired wound healing
Decreased taste and smell acuity
Plasma : 50-150 µg/dl

Introduction
Total body Cu is 100 mg; quantitatively this
is next to iron and zinc
It is seen in muscles, liver, bone marrow,
brain, kidney, heart and hair
Cu containing enzymes:
Ceruloplasmin, cyt. oxidase, cyt. C, tyrosinase,
lysyl oxidase, ALA synthase, monoamine
oxidase, cytosolic superoxide dismutase,
uricase and phenol oxidase

Requirement & Sources
Infants & children : 1.5-3 mg/day
Adults : 2-3 mg/day
Sources:
• Cereals, meat, liver, kidney, egg yolk, nuts
and green leafy vegetables
• Milk is a poor source

Absorption
Mainly from duodenum and is mediated by
a Cu binding protein (metallothioneinmetallothionein)
Only about 10% of dietary Cu is absorbed
Rate of absorption is reducedreduced by phytates,
Ca, Fe, Zn and Mo in the intestines
Storage: liver & bone marrow
Transport: albumin

Excretion: bile
Urine doesn't contain Cu in normal
circumstances
Plasma copper: 100-200 µg/dl
 95% is tightly bound to ceruloplasminceruloplasmin
 Small fraction (5%) is loosely held to
histidine residues of albumin
 Normal serum conc. of ceruloplasmin: 25-50
mg/dl

Deficiency
microcytic normochromic anemiamicrocytic normochromic anemia
Fragility of arteries, deminiralization of bones,
demyelination of neural tissue, myocardial
fibrosis, hypopigmentation of skin, greying of hair
Minke’s kinky hair syndrome: results from
defective cross linking of connective tissue due to
Cu deficiency

Wilson’s hepatolenticular degeneration
Rare (1 in 50,000)
Cu deposition
Liver : hepatic cirrhosis
Brain (lenticular nucleus): brain necrosis
Kidney : renal damage
Chronic toxicity may lead to diarrhea and
blue-green discoloration of saliva.

 Least abundant and most toxic of essential
elements
Sources
Plants (varies with soil content), meat, sea foods
Requirements
Children : 10-30 µg/day
Adult male : 40-70 µg/day
female : 45-55 µg/day
Pregnancy & lactation : 65-75 µg/day

Acts as a nonspecific intracellular antioxidantantioxidant by
providing protection against peroxidation in
tissues and cell membranes.
Complementary to vit. EComplementary to vit. E; availability of vit. E
reduces the Se requirement.
Glutathione peroxidaseGlutathione peroxidase protects the cells
against the damage caused by H2O2
.
Protects from developing liver cirrhosis.
Conversion ofT4 toT3 by 5´- deiodinase.5´- deiodinase.

Normal value : 13 µg/dl
 Most of the Se in blood is a part of glutathoineglutathoine
reductase.reductase.
 Inside the cells, it exists as selenocysteineselenocysteine and
selenomethionine.selenomethionine.
Absorption:: duodenum
 Se isSe is carcinogeniccarcinogenic in animals, its oncogenicin animals, its oncogenic
influence in man is not established.influence in man is not established.

Marginal deficiency;Marginal deficiency; when soil content is low.
In animalsIn animals; hepatic necrosis, retarded growth,
muscular degeneration, infertility.
In humansIn humans; congestive cardiomyopathy
(Keshan disease) in China.
Toxicity: selenosisselenosis ( 900 µg/day)
Hair loss, dermatitis, irritability, purple
streaks in nails, falling of nails, diarrhea and
garlicky odor in breath (dimethyl selenide).

‘’Centre for the Cureness’’

Mineral Metabolism

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