LECTURE 9-Phosphorus and Calcium Metabolismfbfbgfbfgb

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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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REGULATION OFREGULATION OF

CALCITRIOLCALCITRIOL


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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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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

LECTURE 9-Phosphorus and Calcium Metabolismfbfbgfbfgb

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