Ammar Akhtar Roll No. 176 2nd Year

8/14/2019 Ammar Akhtar Roll No. 176 2nd Year

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CalcitriolCalcitriol

AMMAR AKHTARAMMAR AKHTAR

Roll No. 176Roll No. 17622ndnd YearYear


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ContentsContents IntroductionIntroduction Calcitriol.......A hormone????Calcitriol.......A hormone????

Synthesis of CalcitriolSynthesis of Calcitriol Conversion of 7-dehydrocholestrol to cholecalciferolConversion of 7-dehydrocholestrol to cholecalciferol

Formation of calcidiolFormation of calcidiol

Conversion of calcidiol to calcitriolConversion of calcidiol to calcitriol Regulation of SynthesisRegulation of Synthesis Transport, Storage and MetabolismTransport, Storage and Metabolism Biochemical ActionsBiochemical Actions

Effect on IntestineEffect on Intestine

Effect on mineralization of BonesEffect on mineralization of Bones

Effect on kidneyEffect on kidney MiscellaneousMiscellaneous


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Calcitriol and PTHCalcitriol and PTH Abnormalities of Calcitriol MetabolismAbnormalities of Calcitriol Metabolism

RicketsRicketsTypes and causesTypes and causesS/SS/S

DiagnosisDiagnosisTreatmentTreatment

OsteomalaciaOsteomalacia

Renal OsteodystrophyRenal Osteodystrophy


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Therapeutic usesTherapeutic uses

Calcitriol and CancerCalcitriol and Cancer Calcitriol and Cell DifferentiationCalcitriol and Cell Differentiation

Treatment of PsoriasisTreatment of Psoriasis

ReferencesReferences AcknowledgementsAcknowledgements


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IntroductionIntroduction

1,25-dihydroxycholecalciferol1,25-dihydroxycholecalciferol

((1,25-(OH)1,25-(OH)22DD33)

)

Active form of Vitamin DActive form of Vitamin D

Chemical Formula CChemical Formula C2727HH

4444OO

33

Molecular mass - 416.64 g/molMolecular mass - 416.64 g/mol

Half Life - 10 hrsHalf Life - 10 hrs


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Calcitriol....ACalcitriol....A

hormone????hormone????cyclopentanoperhydrophenanthrene nucleuscyclopentanoperhydrophenanthrene nucleus synthesis in skin from its precursorsynthesis in skin from its precursor

Feedback controlFeedback control definite target cellsdefinite target cells

mode of action like steroid hormonesmode of action like steroid hormones

Acts in association with other hormonesActs in association with other hormones

short half lifeshort half life


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SynthesisSynthesis Conversion of 7-dehydrocholesterol toConversion of 7-dehydrocholesterol to

cholecalciferolcholecalciferol 7-dehydrocholesterol in animal skin7-dehydrocholesterol in animal skin ultravoilet light mediated non enzymaticultravoilet light mediated non enzymatic

photolysis reaction in malpighian layer ofphotolysis reaction in malpighian layer of

epidermisepidermis 7-dehydrocholesterol7-dehydrocholesterol cholecalciferolcholecalciferol ReactionReaction

directly related to extent of exposuredirectly related to extent of exposure Inversely related to skin pigmentationInversely related to skin pigmentation

Age related loss of 7-dehydrocholesterolAge related loss of 7-dehydrocholesterol


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Conversion of 7-Conversion of 7-

dehydrocholesterol todehydrocholesterol to

cholecalciferolcholecalciferol


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Synthesis of CalcidiolSynthesis of Calcidiol

Specific D binding protein transportsSpecific D binding protein transportsVitamin DVitamin D22 to liverto liver

Hydroxylation at 25 position by 25Hydroxylation at 25 position by 25hydroxylasehydroxylase

EnzymesEnzymes NADPH dependentNADPH dependent

Cytochrome PCytochrome P450450 ReductaseReductase

Cytochrome PCytochrome P450450 Co-enzymesCo-enzymes

MgMg++++

NADPHNADPH

Molecular OMolecular O22

Feedback inhibitionFeedback inhibition


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SynthesisSynthesis


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Regulation ofRegulation of

SynthesisSynthesis Feedback inhibition of 1Feedback inhibition of 1 -hydroxylase-hydroxylase PTHPTH

Serum phosphate levelSerum phosphate level stimulated bystimulated by

decrease indecrease in serumserum calciumcalcium

and/orand/or phosphatephosphate (PO43)(PO43) increase inincrease in

parathyroid hormoneparathyroid hormone (PTH)(PTH) and/orand/or prolactinprolactin levelslevels
http://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Phosphatehttp://en.wikipedia.org/wiki/Phosphatehttp://en.wikipedia.org/wiki/Parathyroid_hormonehttp://en.wikipedia.org/wiki/Parathyroid_hormonehttp://en.wikipedia.org/wiki/Prolactinhttp://en.wikipedia.org/wiki/Prolactinhttp://en.wikipedia.org/wiki/Prolactinhttp://en.wikipedia.org/wiki/Parathyroid_hormonehttp://en.wikipedia.org/wiki/Phosphatehttp://en.wikipedia.org/wiki/Calcium


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Regulation of CalcitriolRegulation of Calcitriol


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Functions of CalcitriolFunctions of Calcitriol

Intestinal absorption of calciumIntestinal absorption of calcium

and phosphateand phosphate

Binds to chromatinBinds to chromatin expression of gene for CBPexpression of gene for CBP

Ca ATPaseCa ATPase

Ca absorption againstCa absorption againstconcentration gradientconcentration gradient


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Functions (contd)Functions (contd)

Mineralization of bones byMineralization of bones by

synthesis of Ca binding proteinssynthesis of Ca binding proteins OsteoclacinOsteoclacin

Alkaline phosphataseAlkaline phosphatase

resorption & mobilization of Caresorption & mobilization of Ca

Renal absorption of Ca and PRenal absorption of Ca and P


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Calcitriol and PTHCalcitriol and PTH


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RicketsRickets

Abnormality in Calcitriol MetabolismAbnormality in Calcitriol Metabolism

Type IType I

Autosomal recessive disorderAutosomal recessive disorder

Defect in 1-Defect in 1--hydroxylase-hydroxylase

Calcidiol not converted to calcitriolCalcidiol not converted to calcitriol

Type IIType II

Autosomal recessive disorderAutosomal recessive disorder

A.A change in zinc fingers of binding site of DNAA.A change in zinc fingers of binding site of DNA Makes receptors non functionalMakes receptors non functional


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DiagnosisDiagnosis

Blood tests:Blood tests: serumserum calciumcalcium serumserum phosphorusphosphorus

serumserum alkaline phosphatasealkaline phosphatase Arterial blood gasesArterial blood gases may revealmay reveal

metabolic acidosismetabolic acidosis X-raysX-rays of affected bonesof affected bones Bone biopsy rarely performed butBone biopsy rarely performed but

confirms rickets.confirms rickets.
http://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Phosphorushttp://en.wikipedia.org/wiki/Phosphorushttp://en.wikipedia.org/wiki/Alkaline_phosphatasehttp://en.wikipedia.org/wiki/Alkaline_phosphatasehttp://en.wikipedia.org/wiki/Arterial_blood_gashttp://en.wikipedia.org/wiki/Arterial_blood_gashttp://en.wikipedia.org/wiki/Metabolic_acidosishttp://en.wikipedia.org/wiki/Metabolic_acidosishttp://en.wikipedia.org/wiki/X-rayhttp://en.wikipedia.org/wiki/X-rayhttp://en.wikipedia.org/wiki/X-rayhttp://en.wikipedia.org/wiki/Metabolic_acidosishttp://en.wikipedia.org/wiki/Arterial_blood_gashttp://en.wikipedia.org/wiki/Alkaline_phosphatasehttp://en.wikipedia.org/wiki/Phosphorushttp://en.wikipedia.org/wiki/Calcium


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TreatmentTreatment

increasing dietary intake ofincreasing dietary intake of

calcium,calcium,

phosphates andphosphates and vitamin D.vitamin D.

Exposure to ultraviolet light (sunshine),Exposure to ultraviolet light (sunshine),

cod liver oilcod liver oil,,

halibut-liver oil, andhalibut-liver oil, and viosterolviosterol
http://en.wikipedia.org/wiki/Cod_liver_oilhttp://en.wikipedia.org/wiki/Cod_liver_oilhttp://en.wikipedia.org/wiki/Ergosterolhttp://en.wikipedia.org/wiki/Ergosterolhttp://en.wikipedia.org/wiki/Ergosterolhttp://en.wikipedia.org/wiki/Cod_liver_oil


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OsteomalaciaOsteomalacia

Insufficient sunlight exposure, especially inInsufficient sunlight exposure, especially indark-skinned subjectsdark-skinned subjects

Insufficient nutritional quantities or faultyInsufficient nutritional quantities or faulty

metabolism ofmetabolism ofvitamin Dvitamin D oror phosphorusphosphorus Renal tubular acidosisRenal tubular acidosis MalnutritionMalnutrition during pregnancyduring pregnancy MalabsorptionMalabsorption syndromesyndrome Chronic renal failureChronic renal failure Therapy with FumadermTherapy with Fumaderm
http://en.wikipedia.org/wiki/Vitamin_Dhttp://en.wikipedia.org/wiki/Vitamin_Dhttp://en.wikipedia.org/wiki/Phosphorushttp://en.wikipedia.org/wiki/Phosphorushttp://en.wikipedia.org/wiki/Renal_tubular_acidosishttp://en.wikipedia.org/wiki/Renal_tubular_acidosishttp://en.wikipedia.org/wiki/Malnutritionhttp://en.wikipedia.org/wiki/Malnutritionhttp://en.wikipedia.org/wiki/Malabsorptionhttp://en.wikipedia.org/wiki/Malabsorptionhttp://en.wikipedia.org/wiki/Chronic_renal_failurehttp://en.wikipedia.org/wiki/Chronic_renal_failurehttp://en.wikipedia.org/wiki/Chronic_renal_failurehttp://en.wikipedia.org/wiki/Malabsorptionhttp://en.wikipedia.org/wiki/Malnutritionhttp://en.wikipedia.org/wiki/Renal_tubular_acidosishttp://en.wikipedia.org/wiki/Phosphorushttp://en.wikipedia.org/wiki/Vitamin_D


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ManifestationsManifestations

aches and pains in the lumbaraches and pains in the lumbar

(lower back) region and thighs(lower back) region and thighs

triradiate pelvistriradiate pelvis waddling gaitwaddling gait

chronicchronic fatiguefatigue
http://en.wikipedia.org/w/index.php?title=Triradiate_pelvis&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Triradiate_pelvis&action=edit&redlink=1http://en.wikipedia.org/wiki/Fatigue_(medical)http://en.wikipedia.org/wiki/Fatigue_(medical)http://en.wikipedia.org/wiki/Fatigue_(medical)http://en.wikipedia.org/w/index.php?title=Triradiate_pelvis&action=edit&redlink=1


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Biochemical findingsBiochemical findings

Biochemical features are similar toBiochemical features are similar to

ricketsrickets.The major fact is a collapsed.The major fact is a collapsed

calcitriol rate in blood or serum.calcitriol rate in blood or serum.

Radiographic characteristicsRadiographic characteristics

Radiological appearances includeRadiological appearances include pseudofracturespseudofractures
http://en.wikipedia.org/wiki/Ricketshttp://en.wikipedia.org/wiki/Ricketshttp://en.wikipedia.org/wiki/Pseudofracturehttp://en.wikipedia.org/wiki/Pseudofracturehttp://en.wikipedia.org/wiki/Pseudofracturehttp://en.wikipedia.org/wiki/Rickets


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Renal OsteodystrophyRenal Osteodystrophy

Loss of renal parenchymaLoss of renal parenchyma

Unable to form calcitriolUnable to form calcitriol


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Calcitriol and CancerCalcitriol and Cancer

Evidence that calcitriol inhibitsEvidence that calcitriol inhibits

cancer cell proliferation and growthcancer cell proliferation and growthand stimulates epidermal celland stimulates epidermal cell

differentiation, while preventingdifferentiation, while preventing

proliferationproliferation

C l i i l d C llC l it i l d C ll


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Calcitriol and CellCalcitriol and Cell

Differentiation, ProliferationDifferentiation, Proliferation

and Growthand Growth Vitamin D treatment of psoriasisVitamin D treatment of psoriasis

disorder in which there is proliferationdisorder in which there is proliferation

of the keratinocytes and a failure toof the keratinocytes and a failure todifferentiate rapidlydifferentiate rapidly

chronic, hereditary recurrent skinchronic, hereditary recurrent skin

disease marked by reddisease marked by red

spots/thickening and plaques coveredspots/thickening and plaques coveredwith scales.with scales.


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Therapeutic UsesTherapeutic Uses


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ReferencesReferences

Harpers Illustrated BiochemistryHarpers Illustrated Biochemistry

Textbook of Medical BiochemistryTextbook of Medical Biochemistry

by MN Chatterjeaby MN Chatterjea Biochemistry by U. SatyanaryanaBiochemistry by U. Satyanaryana


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AcknowledgementsAcknowledgements

Professor DoctorProfessor Doctor

Khawaja MuhammadKhawaja MuhammadFayyazFayyaz

Faculty of BiochemistryFaculty of BiochemistryDeptt.Deptt.

Ammar Akhtar Roll No. 176 2nd Year

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