minerals
GANESH DHAKAL
PG MED. BIOCHEMISTRY
J.N.MEDICAL COLLEGE
Definitions & Types
• Minerals are essential for the normal growth
and maintenance of the body.
• Macro minerals (more than 100 mg/day).
• Micro minerals also known as trace elements
(less than 100 mg/day)
Important minerals
• Major elements; calcium, magnesium,
phosphorus, sodium, potassium, chloride,
sulphur.
• Trace elements; Iron, iodine copper,
manganese, zinc, molybdenum, selenium,
fluoride.
Biological role of minerals
• Structural components of bone and teeth; calcium, p, mg,f.
• Structural components of soft tissues such as liver, muscle,
nerve cells: p,k,fe,s etc.
• Fluid balance: Na, k,cl etc.
• Acid base balance: Na, p.
• Nerve cell transmission and muscle contraction: Exchange
of Na & k. helps NT and Ca helps MC.
• Blood coagulation: Ca
Thyroid Hormone activity: Iodine.
Vit.B12 : cobalt
Hb &Heme containing compounds: Iron.
CALCIUM
• Total calcium in the body is about 1-1.5 kg.
• 99% seen in bone and 1% in ECF.
Daily req.:500 mg/day
child:1200mg/day
Source: milk good source
egg, fish and veg. medium source
cereals contain small amount.
Absorption
• Absorption: first and second part of
duodenum against a conc. Gradient. And req.
energy.
• Factors causing increased absorption:
Vit D, PTH, Acidity, lysine and arginine.
• Factors causing decreased absorption:
Phytic acid(cereals),oxalates(lefty vegetables)
malabsorption syndromes, high phosphate.
Role of calcium
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Muscles contraction
Nerve conduction
Coagulation
Secretion of hormones(calcitonin, ADH, PTH)
Secondary messenger(glucagon)
Activation of enzymes (Pyruvatekinase, lipase)
Prolongs systole
Bone & teeth formation.
Calpains
• Family of calcium-dependent,cysteine
proteases(proteolytic enzymes).
• Seen ubiquitously in mammals.
• Calpain I & calpain II isoforms share small(30k)
subunit, large (80k) subunit.
Role: cell mobility, cell cycle progression,
potentiation in neurons and cell fusion in
myoblasts.
• Hyperactivity of calpain :Alzheimer’s dzs
cataract formation
myocardial ischemia
cerebral ischemia.
NOTE:
Increase in conc. Calcium in all cell results in calpain
activation, which lead to unregulated proteolysis
and result irreversible tissue damage .
Blood calcium level
• Normal blood level: 9-11 mg%
• 10mg% of ca++=5mEq/L)
• Ionized calcium: about 5 mg%
• Protein bound calcium: about 4 mg%
Factors regulating blood calcium level
Calcium homeostasis
• There are effective controls to maintain this
narrow range of blood calcium (9-11 mg/dl).
• Vitamin D(calcitriol).
• Parathyroid Hormone(PTH)
• Calcitonin.
• Vitamin D:
It has hypercalcemic effect.
It increases the blood calcium level.
It has three major independent sites of
action: Intestine,
kidney
bones.
A. Vitamin D and Absorption of
Calcium
• Calcitriol promotes the absorption of calcium and
• phosphorus from the intestine.
• In the brush-border surface, calcium is absorbed passively.
From the intestinal cell to blood, absorption of calcium needs
energy.
It is either by the sodium-calcium exchange mechanism or
by pumping out the calcium-calbind incomplex.
Calcitriol acts like a steroid hormone.
• It enters the target cell and binds to a cytoplasmic
• receptor.
• The hormone-receptor complex interacts
• with DNA and causes derepression and
consequent
• transcription of specific genes that code for
• Calbindin . Due to the increased
• availability of calcium binding protein, the
absorption of calcium is increased.
B. Effect of Vitamin D in Bone
• Mineralization of the bone is increased by
• increasing the activity of osteoblasts.
• Calcitriol coordinates the remodelling action of
• osteoclasts and osteoblasts.
• It produces the differentiation of osteoclast precursors
from multinucleated cells of osteoblast lineage.
• Calcitriol stimulates osteoblasts which secrete alkaline
• phosphatase. Due to this enzyme, the local
• concentration of phosphate is increased.
• The ionic product of calcium and phosphorus
increases, leading to mineralization
C. Effect of Vitamin D in Renal Tubules
• Calcitriol increases the reabsorption of
calcium and phosphorus by renal tubules,
therefore both minerals are conserved.
D. Regulation of Calcitriol
• The hormonal level of calcitriol is maintained
by the feed back control.
• The rate of production is modulated by serum
• levels of calcium, phosphorus, PTH and
calcitriol itself.
• The major site of control is on the 1-alphahydroxylase of kidney.
• Hypercalcemia decreases calcitriol.
• Low dietary calcium and hypocalcemia increase
the rate of production of 1,25-DHCC.
• The stimulatory effect of hypocalcemia on 1alpha hydroxylaseis through PTH.
• Hypercalcemia decreases calcitriol.
• The half-life of 1, 25-DHCC is 6-8 hours.
• Parathyroid hormone (PTH):
• It has a hypercalcemic hormone.
• It has three major sites of action: Intestine
Kidney
Bones
Mechanism of Action of PTH
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PTH binds with a receptor protein (Mol. wt.
70,000 Daltons) on the surface of target cells.
This activates adenyl cyclase with consequent
increase in intracellular calcium concentration.
A kinase is activated and enzyme systems are
activated.
• The PTH has three major independent sites of
action; bone kidney and intestine
PTH and bones: causes
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In the bone, PTH cause demineralization or decalcification
• It induces pyrophosphatase in the osteoclasts.
• The numbers of osteoclasts are also increased.
• Osteoclasts release lactate into surrounding medium which solubilizes
calcium.
PTH also causes secretion of collagenase from osteoclasts.
• This causes loss of matrix and bone resorption.
• As a consequence, mucopolysaccharidesand hydroxyproline are excreted
in urine.
PTH and kidney
• : In kidney, PTH causes
• decreased renal excretion of calcium and
• increased excretion of phosphates.
The action is mainly through increase in
reabsorption of calcium from kidney tubules
• PTH and intestines: PTH stimulates 1hydroxylation
• of 25-hydroxycalciferol in kidney to
• produce calcitriol. This indirectly increases
• calcium absorption from intestine.
• Calcitonin:
• Secreated by parafollicular cells of thyroid gland.
• Tumor marker .
• It is hypocalcemic hormone,which decreases the
blood calcium level.
• Site of Action; Kidney and bone
• Calcitonin level is increased in medullary
carcinoma of thyroid and therefore, is a tumor
marker.
• The level is also increased in multiple
endocrine neoplasia (MEN).
Hypercalcitoninemia
• may also result from ectopic calcitonin
production from malignant tumors of the lung
and bronchus.
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Calcitonin decreases serum calcium level. It
inhibits resorption of bone. It decreases the
activity of osteoclasts and increases that of
osteoblasts.
Calcitonin and PTH are directly antagonistic.
Calcitonin,Calcitriol &PTH Act Together
• When blood level calcium tends to lower, PTH
secretion is stimulated and Calcitonin is
inhibited: bone demineralization leads to
entry of more calcium into blood.
• When blood calcium is increased, PTH is
inhibited and calcitonin is secreted, causing
more entry of calcium into bone.
Calcitonin and Calcitriol are Different
• Calcitonin is the peptide hormone released
from thyroid gland. It decreases blood calcium
level.
• Calcitriol is the active form of vitamin D. It
• increases the blood calcium
Functions of Phosphate Ions
• 1. Formation of bone and teeth.
• 2. Production of high energy phosphate compounds
such as ATP, CTP, GTP, creatine phosphate, etc.
• 3. Synthesis of nucleoside co-enzymes such as NAD
and NADP.
• 4. DNA and RNA synthesis, where phosphodiester
linkages form the backbone of the structure.
• 5. Formation of phosphate esters such as
glucose-6-phosphate, phospholipids.
• 6. Formation of phosphoproteins, e.g. casein.
• 7. Activation of enzymes by phosphorylation.
• 8. Phosphate buffer system in blood. The ratio of
Na2HPO4 : NaH2PO4 in blood is 4:1at pH of 7.4.
Phosphate level also has an effect on
calcium homeostasis:
• Hypophosphatemia increases the serum
calcium level.
• Hypophosphatemia enhances the
hydroxylation of vitamin D in kidneys to form
calcitriol, which has hypercalcemic effect.
When to check calcium level?
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Neurological symptoms,irritability, seizures
Renal calculi
Ectopic calcification
Suspected malignancies
Polyuria &polydypsia
Chronic renal failure
Prolonged drug treatment, which cause
hypercalcemia (thiazide diuretics)
Phosphate level is to checked
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Renal tubular dzs
Hyperparathyroidism
Hypoparathyroidism
Bone dzs such as ricket
Muscle weakness
Causes of Hyperphosphatemia
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1. Increased absorption of phosphate
Excess vitamin D
Phosphate infusion
2. Increased cell lysis
Chemotherapy for cancer
Bone secondaries
Rhabdomyolysis
3. Decreased excretion of phosphorus
Renal impairment
Hypoparathyroidism
4. Hypocalcemia
5. Massive blood transfusions
6. Thyrotoxicosis
7. Drugs
Chlorothiazide, Nifedipine, Furosemide
Causes of Hypophosphatemia
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1. Decreased absorption of phosphate
Malnutrition
Malabsorption
Chronic diarrhea
Vitamin D deficiency
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2. Intracellular shift
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Insulin therapy, glucose phosphorylation
Respiratory alkalosis
3. Increased urinary excretion of phosphate
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Hyperparathyroidism
Fanconi's syndrome
Hypophosphatemic rickets
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4. Hereditary hypophosphatemia
5. Hypercalcemia
6. Chronic alcoholism
7. Drugs
Antacids, Diuretics, Salicylate intoxication
Important Combinations of Serum
Calcium and Phosphate Levels in Blood
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1. Increased P with decreased Ca
Hypoparathyroidism
Renal disease
2. Increased P with normal or increased Ca
Milk alkali syndrome
Hypervitaminosis D
3. Decreased P with increased Ca
Hyperparathyroidism
Sarcoidosis
4. Decreased P and Ca
Malabsorption
Vitamin D deficiency
Renal tubular acidosis
Magnesium
• MAGNESIUM (Mg++) Magnesium is the fourth
most abundant cation in the body and second
most prevalent intracellular cation.
• Magnesium is mainly seen in intracellular
fluid. Total body magnesium is about 25 g,
60% of which is complexed with calcium in
bone.
Functions of Magnesium
• 1. Mg++ is the activator of many enzymes
requiring ATP. Alkaline phosphatase, hexokinase,
fructokinase, phosphofructokinase, adenyl
cyclase, cAMP dependent kinases, etc. need
magnesium.
• 2. Neuromuscular irritability is lowered by
magnesium.
• 3. Insulin-dependent uptake of glucose is
reduced in magnesium deficiency. Magnesium
supplementation improves glucose tolerance.
• SULFUR Source of sulfates is mainly amino
acids cysteine and methionine. Proteins
contain about 1% sulfur by weight. Inorganic
sulfates of Na+, K+ and Mg++, though
available in food, are not utilized.
Functions of Sulfur
• 1. Sulfur containing amino acids are important
constituents of body proteins. The disulfide
bridges keep polypeptide units together, e.g.
insulin, immunoglobulins.
• 2. Chondroitin sulfates are seen in cartilage and
bone.
• 3. Keratin is rich in sulfur, and is present in hair
and nail.
• 4. Many enzymes and peptides contain -SH group
at the active site, e.g. glutathione.
• 5. Co-enzymes derived from thiamine, biotin,
pantothenic acid and lipoic acid also contain
sulfur.
• 6. If sulfate is to be introduced in
glycosaminoglycans or in phenols for
detoxification, it can be done only by
phosphoadenosine phosphosulfate (PAPS).
• 7. Sulfates are also important in detoxification
mechanisms, e.g. production of indoxyl sulphate
IRON (Fe)
• Distribution of iron Total body iron content is
3 to 5 gm; 75% of which is in blood, the rest is
in liver, bone marrow and muscles. Iron is
present in almost all cells.
• Heme containing proteins are shown in Table
35.2. Blood contains 14.5 g of Hb per 100 ml.
About 75% of total iron is in hemoglobin, and
5% is in myoglobin and 15% in ferritin.
Heme-containing proteins
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Hemoglobin Myoglobin Cytochrome oxidase
Cytochrome
Cytochrome c1
Cytochrome c
Cytochrome b5
Cytochrome p-450
Catalase
Nonheme Iron-containing Proteins
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Aconitase
Phe-hydroxylase
Transferrin
Plasma Ferritin
Tissues Hemosiderin
COPPER (Cu)
• Total body copper is about 100 mg.
• It is seen in muscles, liver, bone marrow,
brain, kidney, heart and in hair.
• Copper containing enzymes are
ceruloplasmin, cytochrome oxidase,
cytochrome c, tyrosinase, lysyl oxidase, ALA
synthase, monoamine oxidase, superoxide
dismutase and phenol oxidase
Functions of Copper
• 1. It is necessary for iron absorption and
incorporation of iron into hemoglobin.
• 2. It is necessary for tyrosinase activity.
• 3. It is a co-factor for vitamin C requiring
hydroxylations.
• 4. It increases HDL and so protects the heart.
Fluoride
• Fluoride is known to prevent caries.
• Caries is a Latin term, meaning "decay".
• In the pits and fissures of premolar and molar
teeth, bacterial fermentation of residual food
leads to acid production
FLuorosis is More Dangerous Than
Caries
• Fluoride level more than 2 ppm will cause chronic
intestinal upset, gastroenteritis, loss of appetite
and loss of weight.
• Level more than 5 ppm causes mottling of
enamel, stratification and discoloration of teeth.
• A level more than 20 ppm is toxic, leading to
alternate areas of osteoporosis and
osteosclerosis, with brittle bones.
• This is called fluorosis.
ZINC (Zn)
• Total zinc content of body is about 2 gm, out
of which 60% is in skeletal muscles and 30% in
bones.
• Highest concentration of zinc is seen in
hippocampus area of brain and prostatic
secretion.
• In liver, zinc is stored in combination with a specific
protein, metallothionein. Zinc is excreted through
pancreatic juice and to a lesser extent through sweat.
• More than 300 enzymes are zinc-dependent.
• Some important ones are carboxypeptidase, carbonic
anhydrase, alkaline phosphatase, lactate
dehydrogenase, alcohol dehydrogenase and glutamate
dehydrogenase. RNA polymerase contains zinc and so
it is required for protein biosynthesis. Extracellular
superoxide dismutase is zinc dependent and so, zinc
has antioxidant activity.
• Insulin when stored in the beta cells of
pancreas contains zinc, which stabilizes the
hormone molecule. But the insulin released
into the blood does not contain zinc. The
commercially available preparation, protaminzinc-insulinate (PZI) also contains zinc. Zinc
containing protein, Gusten, in saliva is
important for taste sensation.
Zinc deficiency manifestations
• Poor wound healing, lesions of skin, impaired
spermatogenesis, hyperkeratosis, dermatitis and
alopecia are deficiency manifestations of zinc.
• There is reduction in number of T and B
lymphocytes.
• Macrophage function is retarded. Zinc deficiency
leads to depression, dementia and other
psychiatric disorders. Zinc binds with amyloid to
form a plaque in Alzheimer's disease
• SELENIUM (Se) Selenium intake depends on
the nature of the soil in which food crops are
grown. Requirement is 50-100 microgram/day.
Normal serum level is 50-100 microgram/dl.
• In mammals, glutathione peroxidase (GP) is
the important selenium containing enzyme.
RBC contains good quantity of glutathione
peroxidase. Thyroxin is converted to T3 by 5'de-iodinase, which is a selenium containing
enzyme.
• In Se deficiency, this enzyme becomes less
active, leading to hypothyroidism.
• Selenium concentration in testis is the highest
in adult tissue.
• It is necessary for normal development of
spermatozoa. It is concentrated in the midpiece of spermatozoa as a specific selenoprotein in mitochondria
MANGANESE (Mn)
• Total body manganese is 15 mg. Maximum
concentration is in liver (1.5 ppm). In the cells,
it is mainly seen inside the nuclei, as
complexed with nucleic acids.
Functions:
• The following enzymes either contain or are
activated by manganese: Hexokinase,
phosphoglucomutase, pyruvate carboxylase,
isocitrate dehydrogenase, succinate
dehydrogenase, arginase, glutamine
synthetase
• Mndependent superoxide dismutase.
Manganese is an integral part of glycosyl
transferases, responsible for synthesis of
glycoproteins and chondroitin sulfate. Mn is
also required for RNA polymerase activity.