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.