cyt c oxidase.ppt

cytochrome c

1. Cytochrome C Oxidase

2. Introduction
•Cytochromecoxidase(EC1.9.3:1)istheterminal
enzymeoftherespiratorychainsofmitochondria
andaerobicbacteria.
•Electrontransferiscoupledtoprotontranslocation
acrossthemembrane,resultinginaprotonand
chargegradientthatisthenemployedbytheF
0F
1-
ATPasetosynthesizeATP.
•Defectsincytochromecoxidasefunctionarefound
inaclinicallyheterogeneousgroupofdisorders.
•Mostlyasaresultofgeneticdefectsofitsgenes,
especiallythosethatencodeassemblyproteins-
SURF1,SCO1,SCO2,COX10,andCOX15.

3. Introduction (con’d)
•Humancytochromecoxidaseiscomposedof13
subunits.
•threemajorsubunitsformthecatalyticcoreandare
encodedbymitochondrialDNA(mtDNA).
•Theremainingsubunitsarenuclear-encoded.
•Thecomplexcontainstwohemes,acytochrome
aandcytochromea
3,andtwocoppercenters,the
Cu
AandCu
Bcenters;thecytochromea
3andCu
Bform
abinuclearcenterthatisthesiteofoxygenreduction.
•Inpost-assemblymodifications,theenzymeis
dimerized,connectedbyacardiolipinmolecule,
whichisrequiredforactive/efficientenzymeaction.

4. Electron Transport Chain

5. Mitochondrial

6. The proton pumps are Complexes I,
III and IV.
Protons return thru ATP synthase

7. COMPLEX IV

8. The crystal structure of bovine cytochromecoxidase in a phospholipid bilayer

9. Summary
•Cytochromecoxidase(COX),theterminalenzyme
ofthemitochondrialrespiratorychain,isoneofthe
keyfunctionalandregulatorysitesofthe
mammalianenergymetabolism.
•Owingtotheimportanceoftheenzyme,
pathogeneticmutationsaffectingCOXfrequently
resultinsevere,oftenfatalmetabolicdisorders.
•Nosatisfactorytherapyiscurrentlyavailablesothat
thetreatmentremainslargelysymptomaticand
doesnotimprovethecourseofthedisease.

10. Summary
•Mostofthesemutationsarelocatedingenes
encodingCOX-specificassemblyproteinsincluding
SURF1,SCO1,SCO2,COX10,andCOX15.
•Despitetheidentificationofincreasingnumberof
mutations,theirpreciseetiopathogenetic
mechanisms,whicharenecessaryforthe
developmentoffuturetherapeuticprotocols,still
remaintobeelucidated.