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8/8/2019 LECTURE 9-Phosphorus and Calcium Metabolismfbfbgfbfgb
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DML BiochemistryDML Biochemistry 11
PHOSPHORUS ANDPHOSPHORUS AND
CALCIUM METABOLISMCALCIUM METABOLISM
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DML BiochemistryDML Biochemistry 22
CALCIUM &CALCIUM &
PHOSPHORUSPHOSPHORUS Calcium :Calcium :
The mostabundant mineral in the bodyThe mostabundant mineral in the body
99% ofbodys calcium is present in bone99% ofbodys calcium is present in bonetogether with phosphate as mineraltogether with phosphate as mineral
hydroxyapatitehydroxyapatite Phosphorus :Phosphorus :
Important element in the human bodyImportant element in the human body
80% of phosphorus combine with calcium in80% of phosphorus combine with calcium inbones & teethbones & teeth
Present in the form of organic (phospholipids) &Present in the form of organic (phospholipids) &inorganic phosphate (mixture of HPO4inorganic phosphate (mixture of HPO4-- &&H2PO4H2PO4--))
Ratio of calcium to phosphorus 2:1Ratio of calcium to phosphorus 2:1
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DML BiochemistryDML Biochemistry 33
FUNCTION OF CALCIUMFUNCTION OF CALCIUM
Physiologically calcium is classified as eitherPhysiologically calcium is classified as eitherintracellular or extracellular.intracellular or extracellular.
Function of intracellular calcium:Function of intracellular calcium: Muscle contractionMuscle contraction is initiated by the binding ofis initiated by the binding of
calcium to troponine.calcium to troponine.
Release of hormoneRelease of hormone requires calcium ionsrequires calcium ions
Regulation of enzyme activityRegulation of enzyme activity activation ofactivation ofenzyme or binding proteins requires ca2+ asenzyme or binding proteins requires ca2+ asspecific cofactorspecific cofactor
Cell divisionCell division involve in the process of mitosisinvolve in the process of mitosis
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DML BiochemistryDML Biochemistry 44
FUNCTION OF CALCIUMFUNCTION OF CALCIUM
Functions as extracellular calciumFunctions as extracellular calcium
Formation ofbone & teethFormation ofbone & teeth major mechanicalmajor mechanical
constituents ofbone. The hardness & rigidity ofconstituents ofbone. The hardness & rigidity ofbone & teeth are due to hydroxyapatite.bone & teeth are due to hydroxyapatite.
Blood coagulationsBlood coagulations calcium present in plateletscalcium present in plateletsinvolved blood coagulation (conversion ofinvolved blood coagulation (conversion of
prothrombin into thrombin)prothrombin into thrombin) Cardiac activityCardiac activity cardiac muscle contractioncardiac muscle contraction
relies on extracellular calcium. If ca2+ deprived,relies on extracellular calcium. If ca2+ deprived,it ceases to beat within approx 1 min.it ceases to beat within approx 1 min.
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DML BiochemistryDML Biochemistry 55
FUNCTION OFFUNCTION OF
PHOSPHORUSPHOSPHORUS Constituents ofbone & teethConstituents ofbone & teeth inorganic phosphateinorganic phosphate
major constituent of hydroxyapatite in bonemajor constituent of hydroxyapatite in bone AcidAcid--base regulationbase regulation HPO4 & H2PO4 constitutesHPO4 & H2PO4 constitutes
phosphate buffer which plays a role in maintainingphosphate buffer which plays a role in maintainingpH.pH.
Energy storage & transfer reactionsEnergy storage & transfer reactions EnergyEnergycompound (ATP, ADP & creatine phosphate)compound (ATP, ADP & creatine phosphate)
Essential constituentsEssential constituents essential element inessential element in
phospholipid of cell membrane, nucleic acid (RNA &phospholipid of cell membrane, nucleic acid (RNA &DNA)DNA) Enzyme actionEnzyme action -- present in nucleotides whichpresent in nucleotides which
function as coenzyme such as pyridoxal phosphate,function as coenzyme such as pyridoxal phosphate,thiamine phyrophosphate, etc.thiamine phyrophosphate, etc.
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DML BiochemistryDML Biochemistry 66
SOURCE OF CALCIUM &SOURCE OF CALCIUM &
PHOSPHORUSPHOSPHORUS CalciumCalcium
Dietary source: milk & dairy products, cheese,Dietary source: milk & dairy products, cheese,cereal grains, legumes & nutscereal grains, legumes & nuts
Recommended daily allowance : 800mgRecommended daily allowance : 800mg adults,adults,1200mg1200mg pregnancy women, breast feedingpregnancy women, breast feedingmothers & teenagersmothers & teenagers
PhosphorusPhosphorus Dietary source : milk, cheese, beans, eggs,Dietary source : milk, cheese, beans, eggs,
cereals, fish & meat.cereals, fish & meat. Recommended daily allowance : 800 mgRecommended daily allowance : 800 mg bothboth
men & women, 1200mgmen & women, 1200mg during pregnancy &during pregnancy &lactation.lactation.
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DML BiochemistryDML Biochemistry 77
DISTRIBUTION OF CALCIUMDISTRIBUTION OF CALCIUM
& PHOSPHORUS& PHOSPHORUS
CalciumCalcium stored in bone (99%), ionizedstored in bone (99%), ionizedfrom circulating in serum (10mg/100ml)from circulating in serum (10mg/100ml)
NonNon--ionized formed bound to protein; smallionized formed bound to protein; smallamountabsorbed by the small intestinesamountabsorbed by the small intestines
Normal serum calcium concentration : 8.8Normal serum calcium concentration : 8.8--10.4 mg/dL10.4 mg/dL
Normal serum phosphorus concentration :Normal serum phosphorus concentration :2.52.5--4.5 mg/dL4.5 mg/dL
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DML BiochemistryDML Biochemistry 88
250 mg/day of calcium turn over in the skeleton250 mg/day of calcium turn over in the skeleton mediated by osteoblastand osteoclasts;mediated by osteoblastand osteoclasts;hyperparathyroidism and hypoparathyroidismhyperparathyroidism and hypoparathyroidism
1515--20% calcium absorbed by duodenum and20% calcium absorbed by duodenum andtransported to ileum. Absorption effected by lowtransported to ileum. Absorption effected by lowdietary calcium, growth, pregnancy and lactationdietary calcium, growth, pregnancy and lactation
Acidic food eg. Oxalates binds to the calciumAcidic food eg. Oxalates binds to the calcium calcium unable to usecalcium unable to use
High fatty foodHigh fatty food impede calcium absorptionimpede calcium absorption PhosphatesPhosphates should be regularly replaced as it isshould be regularly replaced as it is
continually being excretedcontinually being excreted
DISTRIBUTION OF CALCIUMDISTRIBUTION OF CALCIUM
& PHOSPHORUS& PHOSPHORUS
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DML BiochemistryDML Biochemistry 99
CALCIUM METABOLISMCALCIUM METABOLISM
Absorption ofbetween 20% and 70%Absorption ofbetween 20% and 70%
Most efficientabsorption : duodenumMost efficientabsorption : duodenum
Bulk ofabsorption : jejunum and ileumBulk ofabsorption : jejunum and ileum(anatomic length)(anatomic length)
Absorption by active transportAbsorption by active transport(duodenum, control of 1,25(duodenum, control of 1,25--(OH)2D3)(OH)2D3)facilitated diffusion)facilitated diffusion)
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DML BiochemistryDML Biochemistry 1010
CALCIUM METABOLISMCALCIUM METABOLISM
Factors affecting absorptionFactors affecting absorption
Amount of soluble calcium saltAmount of soluble calcium salt absorbedabsorbedrapidly.rapidly.
The pHThe pH cal
cium sal
t more solubl
e inacid th
anc
alcium s
alt more so
lubl
e inacid th
anin basic solutionin basic solution
CalciumCalcium--phosphorus ratio in dietphosphorus ratio in diet should be inshould be in1:2 to 2:1. absorption is max when food1:2 to 2:1. absorption is max when foodcontains almost equalamounts of calcium &contains almost equalamounts of calcium &
phosphorusphosphorus The state of fat digestion & absorptionThe state of fat digestion & absorption failurefailureof fat digestion & absorption reduce absorptionof fat digestion & absorption reduce absorptionofboth calcium & phosphorusofboth calcium & phosphorus
PTH & vit DPTH & vit D stimulate calcium absorption.stimulate calcium absorption.
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DML BiochemistryDML Biochemistry 1111
CALCIUM METABOLISMCALCIUM METABOLISM
Factors stimulate calcium absorptionFactors stimulate calcium absorption
LactoseLactose increase absorption of calcium byincrease absorption of calcium by
forming soluble complex with calcium ionsforming soluble complex with calcium ions Amino acids with basic chains lysine & arginineAmino acids with basic chains lysine & arginine
increase calcium absorptionincrease calcium absorption
Vit DVit D important stimulating factor of calciumimportant stimulating factor of calcium
absorptionabsorption Parathyroid HormoneParathyroid Hormone stimulate calciumstimulate calcium
absorption indirectly viaactivating vit D.absorption indirectly viaactivating vit D.
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DML BiochemistryDML Biochemistry 1212
CALCIUM METABOLISMCALCIUM METABOLISM
Factors that inhibit calcium absorptionFactors that inhibit calcium absorption
Phytic acidPhytic acid binds to dietary calcium formingbinds to dietary calcium forminginsoluble complexes which notabsorbed byinsoluble complexes which notabsorbed by
intestine.intestine. Obstruction ofbile duct or defective bile saltObstruction ofbile duct or defective bile salt
supplysupply leads to deficiency of vit D thusleads to deficiency of vit D thusimpaired calcium absorptionimpaired calcium absorption
Coeliac diseaseCoeliac disease interfere with vit D absorptioninterfere with vit D absorption& consequently absorption of calcium& consequently absorption of calcium
Excretion of calciumExcretion of calcium through kidneys but mostlythrough kidneys but mostlyexcrete via small intestine through feces. Smallexcrete via small intestine through feces. Smallamount of calcium may be lost in sweatamount of calcium may be lost in sweat
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DML BiochemistryDML Biochemistry 1313
PLASMA CALCIUMPLASMA CALCIUM
Plasma calcium concentration in normal person approx 2 to 3Plasma calcium concentration in normal person approx 2 to 3mg.mg.
3 forms:3 forms:
Free or unbound or ionic calcium (Ca2+)Free or unbound or ionic calcium (Ca2+) 50%50% Bound calciumBound calcium 40% bound to albumin40% bound to albumin Complexed calciumComplexed calcium 10% is complexed with anions10% is complexed with anions
(HCO3(HCO3--, H2PO4), lactate & citrate, H2PO4), lactate & citrate All 3 forms are equilibrium with one another.All 3 forms are equilibrium with one another.
Calcium binds toCalcium binds to --ve charged site on protein, its binding is pHve charged site on protein, its binding is pH
dependentdependent AlkalosisAlkalosis an increase inan increase in --ve charge & binding, decreaseve charge & binding, decreasein free calciumin free calcium
AcidosisAcidosis decrease indecrease in --ve charge & binding, increase inve charge & binding, increase infree calciumfree calcium
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DML BiochemistryDML Biochemistry 1414
PHOSPHORUSPHOSPHORUS
METABOLISMMETABOLISM Absorption :Absorption :
Phosphorus absorption occurring throughout thePhosphorus absorption occurring throughout the
small intestine. (60~80%)small intestine. (60~80%) Uptake from the gut is due to a combination ofUptake from the gut is due to a combination of
an inhibitable sodium phosphate cotransporteran inhibitable sodium phosphate cotransporterand diffusion down a concentration gradientand diffusion down a concentration gradient
Phosphate absorption: 1,25Phosphate absorption: 1,25--(OH)2D3 on calcium(OH)2D3 on calciumtransport enhanced intestinalalkalinetransport enhanced intestinalalkalinephosphatase activityphosphatase activity
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DML BiochemistryDML Biochemistry 1515
PHOSPHORUSPHOSPHORUS
METABOLISMMETABOLISM ExcretionExcretion
Mainly excreted by kidney as NaH2PO4 throughMainly excreted by kidney as NaH2PO4 through
urine.urine. 90% of phosphate filtered through glomeruli is90% of phosphate filtered through glomeruli is
reabsorbed by tubules.reabsorbed by tubules.
PTH decrease reabsorption of phosphorus fromPTH decrease reabsorption of phosphorus from
the proximal & distal convulated tubules & causethe proximal & distal convulated tubules & causeincrease excretion of phosphorus in urineincrease excretion of phosphorus in urine
Only smallamountare excreted in feces.Only smallamountare excreted in feces.
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DML BiochemistryDML Biochemistry 1616
PLASMA PHOSPHORUSPLASMA PHOSPHORUS
Plasma contains approx 2.5 to 4.5Plasma contains approx 2.5 to 4.5mg/dl of inorganic phosphatemg/dl of inorganic phosphate
Calcium & phosphate has reciprocalCalcium & phosphate has reciprocalrelationship. If phosphate rise, calciumrelationship. If phosphate rise, calciumfallsfalls
Control of ECF phosphateControl of ECF phosphateconcentration is achieved by kidneyconcentration is achieved by kidney
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DML BiochemistryDML Biochemistry 1717
HORMONE RELATED TOHORMONE RELATED TO
CALCIUM & PHOSPHORUSCALCIUM & PHOSPHORUS
METABOLISMMETABOLISM
Calcium metabolism:Calcium metabolism: PTHPTH
CalcitoninCalcitonin 1,251,25--DHCCDHCC
Parathyroid hormone (PTH)Parathyroid hormone (PTH)
secreted when serum calcium levellowsecreted when serum calcium levellow promotes calcium resorption in intestinaland osteoclastspromotes calcium resorption in intestinaland osteoclasts
Inhibits phosphate reabsorption by stimulating excretionInhibits phosphate reabsorption by stimulating excretionof phosphates by the kidneysof phosphates by the kidneys
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DML BiochemistryDML Biochemistry 1818
HORMONE RELATED TOHORMONE RELATED TO
CALCIUM & PHOSPHORUSCALCIUM & PHOSPHORUS
METABOLISMMETABOLISM
CalcitoninCalcitonin A hormone which contrary effect with PTHA hormone which contrary effect with PTH
High calcium level stimulates calcitonin secretion thusHigh calcium level stimulates calcitonin secretion thusmoving phosphate from blood to form bone matrixmoving phosphate from blood to form bone matrix
1,251,25-- dihydroxycholecalciferol (1,25dihydroxycholecalciferol (1,25--DHCC)DHCC) A form of vitamin D3, synthesized from 7A form of vitamin D3, synthesized from 7--
dehydrocholesterol in the skin by ultraviolet radiation (UVdehydrocholesterol in the skin by ultraviolet radiation (UVB)B)
Absorbby upper duodenum with chylomicrons & stored inAbsorbby upper duodenum with chylomicrons & stored inglobulin bind with proteinglobulin bind with protein
To increase calcium and phosphate absorption from GITo increase calcium and phosphate absorption from GItract.tract.
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DML BiochemistryDML Biochemistry 1919
ROLE OF PTHROLE OF PTH
Stimulates renal reabsorption of calciumStimulates renal reabsorption of calcium
Inhibits renal reabsorption of phosphateInhibits renal reabsorption of phosphate
Stimulates bone resorptionStimulates bone resorption
Inhibits bone formation andInhibits bone formation andmineralizationmineralization
Stimulates synthesis of calcitriolStimulates synthesis of calcitriol
Net effect of PTHNet effect of PTH serum calcium serum calcium
serum phosphate serum phosphate
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DML BiochemistryDML Biochemistry 2020
REGULATION OF PTHREGULATION OF PTH
Low serum [CaLow serum [Ca+2+2]] Increased PTHIncreased PTHsecretionsecretion
High serum [CaHigh serum [Ca+2+2]] Decreased PTHDecreased PTH
secretionsecretion
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DML BiochemistryDML Biochemistry 2121
ROLE OF CATCITRIOLROLE OF CATCITRIOL
Active form of vitamin DActive form of vitamin D
Stimulates GI absorption ofboth calciumStimulates GI absorption ofboth calcium
and phosphateand phosphate Stimulates renal reabsorption ofbothStimulates renal reabsorption ofboth
calcium and phosphatecalcium and phosphate
Stimulates bone resorption ofboth calciumStimulates bone resorption ofboth calciumand phosphateand phosphate
Net effect of calcitriolNet effect of calcitriol serum calcium serum calcium
serum phosphate serum phosphate
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DML BiochemistryDML Biochemistry 2222
REGULATION OFREGULATION OF
CALCITRIOLCALCITRIOL
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DML BiochemistryDML Biochemistry 2323
ROLE OF CALCITONINROLE OF CALCITONIN
Secretion of calcitonin is stimulated bySecretion of calcitonin is stimulated byincrease in blood calciumincrease in blood calcium
Inhibit calcium reabsorption from bone &Inhibit calcium reabsorption from bone &increase bone calcificationincrease bone calcification
Stimulate renal excretion of calcium &Stimulate renal excretion of calcium &phosphorus; thereby decrease bloodphosphorus; thereby decrease blood
calcium levelcalcium level Involve in counteracting calciumInvolve in counteracting calcium
mobilization action of PTHmobilization action of PTH
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DML BiochemistryDML Biochemistry 2424
REGULATION OF PLASMAREGULATION OF PLASMA
CALCIUM LEVELCALCIUM LEVEL Homeostasis of plasma calcium is dependHomeostasis of plasma calcium is depend
on 3 main organs (bone, kidney & intestine)on 3 main organs (bone, kidney & intestine)& 3 main hormones (PTH, Vit D && 3 main hormones (PTH, Vit D &Calcitonin)Calcitonin)
3 major process to maintain plasma calcium3 major process to maintain plasma calciumlevelslevels Absorption of calcium from intestine throughAbsorption of calcium from intestine through
action of Vit Daction of Vit D Reabsorption of calcium from kidney throughReabsorption of calcium from kidney through
action of PTH & vit Daction of PTH & vit D Dimeneralization ofbone through action of PTHDimeneralization ofbone through action of PTH
but facilitated by Vit Dbut facilitated by Vit D
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