CARBOHYDRATECARBOHYDRATE CARBOHYDRATECARBOHYDRATECARBOHYDRATECARBOHYDRATEMETABOLISMMETABOLISM METABOLISMMETABOLISMMETABOLISMMETABOLISM CONTENTSCONTENTS  IntroductionIntroduction  ClassificationClassification ofof CarbohydratesCarbohydrates  GlycolysisGlycolysis  GlycogenolysisGlycogenolysis  GlycogenesisGlycogenesis  CitricCitric acidacid cyclecycle  PentosePentose phosphatephosphate pathwaypathway  AppliedApplied aspectsaspects  RegulationRegulation ofof BloodBlood glucoseglucose NUTRITIONNUTRITION NutritionNutrition isis defineddefined asas ““thethe sciencescience ofof howhow thethe bodybody utilizesutilizes foodfood toto meetmeet requirementsrequirements forfor developmentdevelopment growth,growth, repairrepair andand maintenance”maintenance” NUTRIENTSNUTRIENTS

CARBOHYDRATES

FATS

PROTEINS

VITAMINS

MINERALS

WATER IntroductionIntroduction

InIn plants,plants, InIn Animals,Animals, Carbondioxide+waterCarbondioxide+water FatFat ++ proteinprotein

GlucoseGlucose carbohydratecarbohydrate (stored(stored asas starchstarch oror convertedconverted toto cellulose)cellulose) BiomedicalBiomedical ImportanceImportance

GlucoseGlucose isis aa majormajor carbohydratecarbohydrate ItIt isis aa majormajor fuelfuel ofof tissuestissues ItIt isis convertedconverted intointo otherother carbohydratescarbohydrates  GlycogenGlycogen forfor storage.storage.  RiboseRibose inin nucleicnucleic acids.acids.  GalactoseGalactose inin lactoselactose ofof milk.milk.  TheyThey formform glycoproteinsglycoproteins && proteoglycansproteoglycans  TheyThey areare presentpresent inin somesome lipoproteinslipoproteins (LDL)(LDL) ..  PresentPresent inin plasmaplasma membrane:glycocalyx.membrane:glycocalyx.  GlycophorinGlycophorin isis aa majormajor intergralintergral membranemembrane glycoproteinglycoprotein ofof humanhuman erythrocytes.erythrocytes. Carbohydrates

Monosaccharides Polysaccharide

Disaccharides Oligosaccharides MonosaccharidesMonosaccharides

Depending on carbon Depending on aldehyde or atoms ketone group •Trioses: Glycerose-Aldo Dihydroxyacetone-Ketone •Aldoses

•Tetroses Erythrose (A) Erythrulose (K) •Ketoses •Pentoses: Ribose (A) Ribulose (K)

•Hexoses: Glucose (A) Fructose (K) •Disaccharides •Maltose •Sucrose

Oligosaccharides •Maltotriose

Polysaccharides •Linear - Starch •Branched- Dextrin METABOLISMMETABOLISM

TheThe entireentire spectrumspectrum ofof chemicalchemical reactions,reactions, occuringoccuring inin thethe livingliving systemsystem areare referredreferred asas “Metabolism”.“Metabolism”.

TypesTypes ofof metabolicmetabolic pathwayspathways  AnabolicAnabolic pathways:pathways: ProteinProtein synthesis.synthesis.  CatabolicCatabolic Pathways:Pathways: OxidativeOxidative phosphorylation.phosphorylation.  AmphibolicAmphibolic pathways:pathways: CitricCitric acidacid cycle.cycle.

FoodFood moleculesmolecules simplersimpler moleculesmolecules

AmphibolicAmphibolic pathwaypathway AnabolicAnabolic CatabolicCatabolic 2H

P

Proteins,Proteins, carbohydrates,carbohydrates, CO2+H2OCO2+H2O lipids,lipids, nucleicnucleic acidsacids etc.etc. MetabolicMetabolic pathwayspathways maymay bebe studiedstudied atat differentdifferent levelslevels ofof organisation.organisation.

 AtAt tissuetissue levellevel  AtAt subcellularsubcellular levellevel OverviewOverviewOverviewOverview ofofofof

CarbohydrateCarbohydrateCarbohydrateCarbohydrate

MetabolismMetabolismMetabolismMetabolism CarbohydratesCarbohydrates  ServeServe asas primaryprimary sourcesource ofof energyenergy inin thethe cellcell  CentralCentral toto allall metabolicmetabolic processesprocesses Glucose Cytosol - anaerobic Hexokinase

Pentose Phosphate Glucose-6-P Glc-1- phosphate Shunt glycolysis glycogen

Pyruvate cytosol Pyruvate mitochondria (aerobic) Acetyl CoA FATTY ACIDS

Krebs Reducing equivalents AMINO cycle ACIDS

Oxidative Phosphorylation (ATP) GLYCOLYSIS GlycolysisGlycolysis

DefnDefn:: ItIt isis defineddefined asas sequencesequence ofof reactionsreactions ofof glucoseglucose toto lactatelactate && pyruvatepyruvate withwith thethe productionproduction ofof ATP.ATP. ItIt isis derivedderived fromfrom greekgreek wordword glycoseglycose -sweet-sweet oror sugar,sugar, lysis-lysis- dissolution.dissolution.

SiteSite:: CytosolicCytosolic fractionfraction ofof cellcell GLYCOLYSIS STAGE I STAGE II STAGE III BioenergeticsBioenergetics inin Glycolysis:Glycolysis: TotalTotal ofof 88 ATPATP isis formedformed inin glycolysis.glycolysis. OxidationOxidation ofof glucoseglucose inin aerobicaerobic condition:38condition:38 ATPATP AnaerobicAnaerobic condition:condition: 22 ATPATP BiomedicalBiomedical importanceimportance ofof GlycolysisGlycolysis

 PrincipalPrincipal routeroute ofof metabolism.metabolism.  ProductionProduction ofof acetylacetyl coAcoA inin citriccitric acidacid cycle.cycle.  MetabolismMetabolism ofof fructosefructose && galactose.galactose.  ProvidesProvides ATPATP inin absenceabsence ofof Oxygen.Oxygen. ClinicalClinical AspectsAspects

 HemolyticHemolytic Anaemias:Anaemias: InheritedInherited aldolasealdolase AA && pyruvatepyruvate kinasekinase deficiencies.deficiencies.  SkeletalSkeletal musclemuscle fatiguefatigue  InheritedInherited PyruvatePyruvate dehydrogenasedehydrogenase deficiency-deficiency- LacticLactic acidosisacidosis  FastFast growinggrowing cancercancer cellscells glycolysisglycolysis proceedsproceeds atat fasterfaster raterate –– increasedincreased acidicacidic environment-environment- implicationimplication inin certaincertain typestypes ofof cancer.cancer. MetabolismMetabolism ofof GlycogenGlycogen

 MajorMajor storagestorage formform ofof carbohydrate.carbohydrate.

 Glycogenesis:Glycogenesis: occursoccurs inin musclemuscle && liver.liver. BiomedicalBiomedical importanceimportance

 LiverLiver glycogenglycogen largelylargely concernedconcerned withwith transporttransport && storagestorage ofof hexosehexose units.units.  ForFor maintenancemaintenance ofof bloodblood glucoseglucose mainlymainly betweenbetween meals.meals. ClinicalClinical aspectsaspects GlycogenGlycogen storagestorage diseasesdiseases TypeType ofof disorderdisorder CauseCause ofof disorderdisorder TypeType II (Von(Von Gierke’sGierke’s Glucose-6-phosphataseGlucose-6-phosphatase disease)disease) deficiency.deficiency. TypeType IIII (Pompe’s(Pompe’s disease)disease) AcidAcid maltasemaltase deficiency.deficiency. TypeType IIIIII (Cori’s(Cori’s disease)disease) DebranchingDebranching enzymeenzyme deficiency.deficiency. TypeType IVIV (Andersen’s(Andersen’s disease)disease) BranchingBranching enzymeenzyme deficiency.deficiency. Muscle phosphorylase TypeType VV (Mcardle’s(Mcardle’s disease)disease) Muscle phosphorylase deficiency.deficiency. TypeType VIVI (Her’s(Her’s disease)disease) LiverLiver phosphorylasephosphorylase deficiency.deficiency.

TypeType VIIVII (Tarui’s(Tarui’s PhosphofructokinasePhosphofructokinase disease)disease) deficiencydeficiency

.. TypeType VIIIVIII LiverLiver phosphorylasephosphorylase kinase.kinase. CITRIC ACID CYCLE BiomedicalBiomedical importanceimportance  FinalFinal commoncommon pathwaypathway forfor oxidationoxidation ofof carbohydrates,carbohydrates, lipidslipids ,, && proteins.proteins.  MajorMajor rolerole inin gluconeogenesis,gluconeogenesis, transamination,transamination, deaminationdeamination && lipogenesis.lipogenesis.  VitaminsVitamins playplay aa keykey rolerole inin thisthis cyclecycle Eg;Eg; RiboflavinRiboflavin –– FAD.FAD. NiacinNiacin –– NAD.NAD. Thiamine.Thiamine. PantothenicPantothenic acidacid asas aa partpart ofof co-A.co-A. BioenergeticsBioenergetics :12:12 ATPATP perper cycle.cycle. PentosePentose PhosphatePhosphate PathwayPathway

AlternativeAlternative routeroute forfor metabolismmetabolism ofof glucoseglucose ItIt occursoccurs inin cytosolcytosol SequenceSequence ofof reactionsreactions occuroccur inin twotwo phasesphases 1.Oxidative1.Oxidative nonnon reversiblereversible phase-Formsphase-Forms NADPHNADPH 2.2. NonNon oxidativeoxidative reversiblereversible phase.-phase.- FormsForms riboseribose precursorsprecursors forfor nucleotidenucleotide synthesis.synthesis.

BiomedicalBiomedical importanceimportance

 GlutathioneGlutathione peroxidaseperoxidase protectsprotects erythrocyteserythrocytes againstagainst hemolysis.hemolysis.  PentosePentose usefuluseful inin synthesissynthesis ofof DNADNA && RNA.RNA.  NADPHNADPH isis requiredrequired forfor reductivereductive biosynthesisbiosynthesis ofof fattyfatty acidsacids && steroids.steroids.  NADPHNADPH isis requiredrequired inin synthesissynthesis ofof aminoamino acids.acids.  MicrosomalMicrosomal cytochromecytochrome P450P450 systemsystem bringsbrings detoxificationdetoxification ofof drugsdrugs && foreignforeign compounds.compounds. ClinicalClinical aspectsaspects

 ErythrocyteErythrocyte hemolysishemolysis  ImpairmentImpairment ofof generationgeneration ofof NADPHNADPH manifestsmanifests asas hemolysishemolysis whenwhen givengiven drugsdrugs likelike Antimalarial-Antimalarial- PrimaquinePrimaquine aspirinaspirin oror sulfonamides.sulfonamides.

(G6(G6 PD)PD) DeficiencyDeficiency::  ItIt makesmakes redred cellscells susceptiblesusceptible toto hemolysishemolysis  XX linkedlinked inheritanceinheritance  OnsetOnset ofof AnaemiaAnaemia isis rapidrapid  MildMild jaundicejaundice

 DefectsDefects inin FructoseFructose metabolismmetabolism  LackLack ofof hepatichepatic fructokinasefructokinase causescauses Fructosuria.Fructosuria.  AbsenceAbsence ofof HepaticHepatic aldolase-Hereditaryaldolase-Hereditary fructosefructose intolerance.intolerance.  Hypoglycemia,Hypoglycemia, vomiting,vomiting, sweating.sweating.  Albuminuria,Albuminuria, aminoaciduria.aminoaciduria.  ReducedReduced cariescaries incidence.incidence. ..  FructoseFructose && sorbitolsorbitol inin lenslens asssociatedasssociated withwith diabeticdiabetic cataract.cataract. GluconeogenesisGluconeogenesis

 SynthesisSynthesis ofof glucoseglucose fromfrom nonnon carbohydratecarbohydrate compoundscompounds isis calledcalled “gluconeogenesis”“gluconeogenesis”  SiteSite :: MainlyMainly occursoccurs inin LiverLiver && kidneykidney matrixmatrix inin cytosol.cytosol.

RegulationRegulation ofof gluconeogenesisgluconeogenesis

 InfluenceInfluence ofof Glucagon.Glucagon.  AvailabilityAvailability ofof substrates.substrates.  AlcoholAlcohol inhibitsinhibits gluconeogenesis.gluconeogenesis. ProteoglycansProteoglycans && GlycosaminoglycansGlycosaminoglycans SevenSeven glycosaminoglycansglycosaminoglycans 11 HyaluronicHyaluronic acidacid 22 ChondriotinChondriotin sulfatesulfate 33 KeratanKeratan sulfatesulfate II 44 KeratanKeratan sulfatesulfate IIII 55 HeparinHeparin 66 HeparanHeparan sulfatesulfate 77 DermatanDermatan sulfatesulfate MucopolysaccharidosesMucopolysaccharidoses

 MPSMPS  DefectDefect MPSMPS II (Hurler(Hurler syndrome)syndrome) Alpha-L-IduronidaseAlpha-L-Iduronidase

MPSMPS IIII (Hunter(Hunter syndrome)syndrome) IduronateIduronate sulfatasesulfatase

MPSMPS IIIAIIIA (Sanfilippo(Sanfilippo A)A) HeparanHeparan sulfatesulfate NN sulfatasesulfatase

MPSMPS IIIBIIIB (Sanfilippo(Sanfilippo B)B) Alpha-AcetylglucosaminidaseAlpha-Acetylglucosaminidase

MPSMPS IIICIIIC (Sanfilippo(Sanfilippo C)C) AcetylAcetyl transferasetransferase  MPSMPS IVAIVA (Morquio(Morquio A)A)  Galactose-6-sulfataseGalactose-6-sulfatase

 MPSMPS IVBIVB (Morquio(Morquio B)B)  BetaBeta galactosidasegalactosidase

 MPSMPS VIVI (Maroteaux(Maroteaux  NN acetylgalactosamineacetylgalactosamine 44 LamyLamy syndrome)syndrome) sulfatasesulfatase

 MPSMPS VIIVII (Sly)(Sly)  BetaBeta glucoronidaseglucoronidase Hunter’s syndrome FunctionsFunctions ofof glycoaminoglycansglycoaminoglycans

 StructuralStructural componentscomponents ofof extracellularextracellular matrix.matrix.  ActAct asas sievessieves inin extracellularextracellular matrix.matrix.  FacilitateFacilitate cellcell migration.migration.  CornealCorneal transparency.transparency.  AnticoagulantAnticoagulant (Heparin).(Heparin).  ComponentsComponents ofof synapticsynaptic && otherother vesicles.vesicles. GlycoproteinsGlycoproteins

OligosaccharideOligosaccharide (glycan)(glycan) covalentlycovalently attachedattached toto theirtheir polypeptidepolypeptide backbones.backbones. GlycoproteinGlycoprotein FunctionsFunctions CollagenCollagen StructuralStructural moleculemolecule MucinsMucins LubricantLubricant && protectiveprotective agentagent TransferrinTransferrin && TransportTransport molecule.molecule. CeruloplasminCeruloplasmin ImmunoglobulinImmunoglobulin moleculemolecule ImmunityImmunity AlkalineAlkaline phosphatasephosphatase EnzymaticEnzymatic activityactivity

RegulationRegulation ofof BloodBlood glucoseglucose

PostabsorptivePostabsorptive statestate:: BloodBlood glucoseglucose isis 4.5-4.5- 5.5mmol/L.5.5mmol/L.

AfterAfter carbohydratecarbohydrate mealmeal:: 6.5-7.2mmol/L6.5-7.2mmol/L

DuringDuring fastingfasting :: 3.3-3.9mmol/L3.3-3.9mmol/L BloodBlood GlucoseGlucose

Glycogenolysis DIET

Gluconeogenesis MetabolicMetabolic && hormonalhormonal mechanismsmechanisms regulateregulate bloodblood glucoseglucose levellevel MaintenanceMaintenance ofof stablestable levelslevels ofof glucoseglucose inin bloodblood isis byby  Liver.Liver.  ExtrahepaticExtrahepatic tissues.tissues.  HormonesHormones .. LiverLiver ExtrahepaticExtrahepatic tissuestissues  FreelyFreely permeablepermeable toto glucoseglucose  RelativelyRelatively impermeableimpermeable viavia GLUT-2GLUT-2 transporter.transporter. toto glucose.glucose.  PassagePassage throughthrough cellcell membranemembrane isis raterate limitinglimiting  PassagePassage isis facilitatedfacilitated step.step. throughthrough variousvarious enzymes.enzymes.

 GlucoseGlucose isis phosphorylatedphosphorylated  ItIt hashas directdirect effecteffect onon entryentry byby hexokinasehexokinase onon entryentry intointo ofof glucoseglucose intointo thethe cell.cell. cellcell

RoleRoleRole Of ofof insulininsulin Insulin RegulationRegulation ofof bloodblood glucoseglucose levelslevels InsulinInsulin AnabolicAnabolic inin responseresponse toto hyperglycemiahyperglycemia LiverLiver  StimulatesStimulates glycogenglycogen synthesis,synthesis, glycolysis,glycolysis, andand fattyfatty acidacid synthesissynthesis MuscleMuscle  StimulatesStimulates glycogenglycogen synthesissynthesis AdiposeAdipose tissuetissue  StimulatesStimulates lipoproteinlipoprotein lipaselipase resultingresulting inin uptakeuptake ofof fattyfatty acidsacids fromfrom chylomicronschylomicrons andand VLDLVLDL  StimulatesStimulates glycolysisglycolysis forfor glycerolglycerol phosphatephosphate synthesissynthesis (precursor(precursor toto triglycerides)triglycerides) RoleRole inin insulininsulin inin loweringlowering bloodblood glucoseglucose GlucagonGlucagon

 ProducedProduced byby AA cellscells ofof isletsislets ofof langerhanslangerhans ofof pancreaspancreas  ActionsActions oppositeopposite toto Insulin.Insulin.  ItsIts secretionsecretion isis stimulatedstimulated byby hypoglycemia.hypoglycemia.  ItIt stimulatesstimulates glycogenolysisglycogenolysis && gluconeogenesisgluconeogenesis fromfrom aminoamino acidsacids && lactate.lactate. RegulationRegulation ofof bloodblood glucoseglucose levelslevels byby GlucagonGlucagon Catabolic,Catabolic, inin responseresponse toto hypoglycemiahypoglycemia LiverLiver  ActivatesActivates glycogenglycogen degradation,degradation, gluconeogenesisgluconeogenesis AdiposeAdipose tissuetissue  StimulatesStimulates lipolysislipolysis andand releaserelease ofof fattyfatty acidsacids RoleRole ofof glucagonglucagon RoleRole ofof thyroidthyroid hormonehormone It stimulates glycogenolysis & gluconeogenesis. HypothyroidHypothyroid HyperthyroidHyperthyroid  FastingFasting bloodblood glucoseglucose isis  FastingFasting bloodblood glucoseglucose isis lowered.lowered. elevatedelevated  PatientsPatients havehave decreaseddecreased  PatientsPatients utiliseutilise glucoseglucose abilityability toto utiliseutilise glucose.glucose. atat normalnormal oror increasedincreased  PatientsPatients areare lessless raterate sensitivesensitive toto insulininsulin thanthan normalnormal oror hyperthyroidhyperthyroid patients.patients. GlucocorticoidsGlucocorticoids

 GlucocorticoidsGlucocorticoids areare antagonisticantagonistic toto insulin.insulin.

 InhibitInhibit thethe utilisationutilisation ofof glucoseglucose inin extrahepaticextrahepatic tissues.tissues.  IncreasedIncreased gluconeogenesisgluconeogenesis ..

EpinephrineEpinephrine

 SecretedSecreted byby adrenaladrenal medulla.medulla.

 ItIt stimulatesstimulates glycogenolysisglycogenolysis inin liverliver && muscle.muscle.

 ItIt diminishesdiminishes thethe releaserelease ofof insulininsulin fromfrom pancreas.pancreas. OtherOther HormonesHormones

AnteriorAnterior pituitarypituitary hormoneshormones GrowthGrowth hormonehormone::  ElevatesElevates bloodblood glucoseglucose levellevel && antagonizesantagonizes actionaction ofof insulin.insulin.  GrowthGrowth hormonehormone isis stimulatedstimulated byby hypoglycemiahypoglycemia (decreases(decreases glucoseglucose uptakeuptake inin tissues)tissues)  ChronicChronic administrationadministration ofof growthgrowth hormonehormone leadsleads toto diabetesdiabetes duedue toto BB cellcell exhaustion.exhaustion. SEXSEX HORMONESHORMONES

 EstrogensEstrogens causecause increasedincreased liberationliberation ofof insulin.insulin.

 TestosteroneTestosterone decreasedecrease bloodblood sugarsugar level.level. HyperglycemiaHyperglycemia HypoglycemiaHypoglycemia  Thirst,Thirst, drydry mouthmouth  SweatingSweating  PolyuriaPolyuria  Trembling,poundingTrembling,pounding  Tiredness,Tiredness, fatiguefatigue heartheart  BlurringBlurring ofof vision.vision.  Anxiety,Anxiety, hungerhunger  Nausea,Nausea, headache,headache,  Confusion,Confusion, drowsinessdrowsiness  HyperphagiaHyperphagia  SpeechSpeech difficultydifficulty  MoodMood changechange  Incoordination.Incoordination.  InabilityInability toto concentrateconcentrate ClinicalClinical aspectsaspects

Glycosuria:Glycosuria: occursoccurs whenwhen venousvenous bloodblood glucoseglucose concentrationconcentration exceedsexceeds 9.5-10.0mmol/L9.5-10.0mmol/L

Fructose-1,6-BiphosphataseFructose-1,6-Biphosphatase deficiencydeficiency causescauses lacticlactic acidosisacidosis && hypoglycemia..hypoglycemia.. DiabetesDiabetes MellitusMellitus

AA multi-organmulti-organ cataboliccatabolic responseresponse causedcaused byby insulininsulin insufficiencyinsufficiency Muscle  ProteinProtein catabolismcatabolism forfor gluconeogenesisgluconeogenesis Adipose tissue  LipolysisLipolysis forfor fattyfatty acidacid releaserelease Liver  KetogenesisKetogenesis fromfrom fattyfatty acidacid oxidationoxidation  GluconeogenesisGluconeogenesis fromfrom aminoamino acidsacids andand glycerolglycerol Kidney  KetonuriaKetonuria andand cationcation excretionexcretion  RenalRenal ammoniagenesis.ammoniagenesis. RoleRole ofof carbohydratescarbohydrates inin dentaldental cariescaries  FermentableFermentable carbohydratescarbohydrates causescauses lossloss ofof cariescaries resistance.resistance.  CariesCaries processprocess isis anan interplayinterplay betweenbetween oraloral bacteria,bacteria, locallocal carbohydratescarbohydrates && toothtooth surfacesurface

BacteriaBacteria ++ Sugars+Sugars+ TeethTeeth OrganicOrganic acidsacids

CariesCaries RoleRole ofof carbohydratescarbohydrates inin periodontalperiodontal

diseasedisease AbnormalAbnormal ExcessiveExcessive carbohydratecarbohydrate glucoseglucose metabolismmetabolism intakeintake

DiabetesDiabetes MellitusMellitus ObesityObesity

PeriodontalPeriodontal diseasedisease PeriodontalPeriodontal diseasedisease ReferencesReferences

 TextText bookbook ofof BiochemistryBiochemistry –Harper.–Harper. Satyanarayan.Satyanarayan. AA CC Deb.Deb.  TextText bookbook ofof PhysiologyPhysiology –Ganong.–Ganong.  TextText bookbook ofof OralOral PathologyPathology –– Shafers.Shafers.  PrinciplesPrinciples && practicepractice ofof Medicine-Davidson.Medicine-Davidson.  NutritionNutrition && oraloral healthhealth –– TheThe DentalDental clinicsclinics ofof NorthNorth America.America. Thank you