Download 3 Physio Enzymes and Glycolysis

Physiology
Unit1
ENZYMESANDCELLULARMETABOLISMOF
GLUCOSEBYGLYCOLYSIS
InPhysiologyToday
CharacteristicsofEnzymes
• Function:Biologicalcatalysts
• Almostallenzymesareproteins
• Speedupchemicalreactionsbyreducingactivation
energy
• Donotthemselvesbecomepartofthereaction
• Donotcatalyzereactionsthatwouldnottakeplace
anyway
• Areveryspecificinthereactionstheycatalyze
Enzymes:OrganicCatalysts
• Livercatalase(theenzyme)
– H2O2 (thesubstrate)
• isanoxidizingagentthatisextremelytoxictocells
– Neutralizedbyanenzyme,catalase,presentin
manytissues
H 2O 2
+
H 2O
H 2O 2
+
catalase
catalase
O2
Enzyme-substrate complex
catalase
Enzyme-SubstrateComplex
• Lockandkeymodel
– Activesiteisthespecificshape(perfectfit)to
accommodatethesubstrate
InducedFitModel
• Substrateinducesashapechangeinthe
activesitethatcreatesthe“perfectfit”
Coenzymes/Cofactors
• Coenzymes areorganicmoleculesthatare
requiredbycertainenzymestocarryout
catalysis
– Coenzymes bindtotheactivesite
• Cofactors areoftenclassifiedasinorganic
substancesthatarerequiredfor,orincrease
therateof,catalysis
– Donotbindtotheactivesite
– Someenzymesrequiremultiplecofactors
Coenzymes
OrganicMolecules
Coenzyme
TransfersorCoenzymefor
NAD+
electrons(2e-)
NADP
electron
FAD
electrons(2e-)
CoA
acylgroup(CH3-C=O)
CoQ
electrons
Thiamine(vitaminB1)
Aldehydes(CHO)
Pyridoxine(vitaminB6)
aminogroups(NH2)
Biotin(vitaminB7)
carbondioxide(CO2)
VitaminB12
alkylgroups(hydrocarbons)
Cofactors
MetalIonsasCofactors
Cofactor
EnzymeorProteinCofactorfor
Zn2+
Carbonicanhydrase
Zn2+
Alcoholdehydrogenase
Fe3+,Fe2+
Cytochromes,hemoglobin
Fe3+,Fe2+
Ferridoxin
Cu2+,Cu+
Cytochromeoxidase
K+,Mg2+
Pyruvatephosphokinase
Ca2+
Na+ channelgating
ReactionRate
• Rateofenzyme-catalyzedreactionsmeasured
bytheratesubstratesareconvertedto
products
• Factorsinfluencingrate:
– Temperature
– pH
– [cofactorsandcoenzyme]
– [enzymeandsubstrate]
– Stimulatoryandinhibitoryeffectsofproductsof
enzymeaction
EffectofTemperature
• Rateofreactionincreases
astemperatureincreases.
• Reactionrateplateaus,
slightlyabovebody
temperature(37o C).
• Reactionratedecreasesas
temperatureincreases.
• Enzymesdenatureathigh
temperatures.
EffectofpH
• Eachenzymeexhibits
peakactivityatnarrow
pHrange(pHoptimum).
• pHoptimumreflectsthe
pHofthebodyfluidin
whichtheenzymeis
found.
• IfpHchanged,soisno
longerwithintheenzyme
range;reactionwill
decrease.
• Why?
Effectof[Substrate]
• Ataspecific[enzyme],
rateofproductformation
increasesasthe
[substrate]increases
• Plateauofmaximum
velocityoccurswhen
enzymeissaturated
• Additional[substrate]
doesnotincreasereaction
rate
RegulatingEnzymeActivity
1.
2.
3.
4.
Allostericmodulation(activators,inhibitors)
Covalentmodulation
Denaturation
Endproductinhibition
Allofthese
involveachange
inthe
conformation of
theenzyme!
Denaturation
• Permanent changeinproteinshape
renderingtheproteinnonfunctional
• temperature,pHchanges
substrate
functional
denatured
EndergonicandExergonicReactions
• Endergonic
– Energyin
– Productsmustcontain
morefreeenergythan
reactants
• Exergonic:
– Energyout
– Convertmoleculeswith
morefreeenergyto
moleculeswithless
– Releaseenergyintheform
ofheat(measuredin
calories)
FormationofATP
• FormationofATP
requirestheinputof
energy
• Thisenergyisreleased
whenATPhydrolyzedto
ADPandpi
– 7Kcal
• ATPistheuniversal
energytransfer
moleculeofthecell
Oxidation-ReductionReactions
•
•
•
•
Reduced=substancegainselectrons
Oxidized=substanceloseselectrons
Redoxreactionsarecoupled
Usuallyinvolvesthetransfer
of2H+ ratherthanfree
Remember….
electrons
Electronshave
tocomefrom
somewhereand
gosomewhere!
MetabolicPathways
Sequenceofenzymaticreactionsthatbeginswith
initialsubstrate,progressesthroughintermediates
andendswithafinalproduct
CellularRespiration
• Glycolysis:
– occursinthecytosol
• Krebscycle:
– occursinthematrixof
themitochondria
• ETS:
– occursonthecristaeof
themitochondria
Glycolysis
• Althoughfats,proteins,andcarbohydrates
canbeusedbythebodyasanenergysource,
glycolysisoperatesonly oncarbohydrates
• Glycolysisisananaerobic process
• Duringglycolysis:
– Glucoseisbrokendowntotwomoleculesof
pyruvicacid(pyruvate)
– Energycarriermoleculesarereduced,producing
ATPandNADH+H+
Glycolysis
Glycolysis