Cytochrome C Flashcards
What is Cytochrome C capable of doing?
Accept electrons and then transfer it off to another protein
Capable of undergoing oxidation and reduction
What doesn’t Cytochrome C bind?
Doesn’t bind to oxygen
What complexes are the electrons transported between?
Complexes III (Coenzymes Q -Cyt C reductase)
IV (Cyt C oxidase)
What allows for the electrons to transport between the two complexes?
Co-factors
In humans what encodes for Cytochrome C?
CYCS gene
How is Cytochrome C involved in Phosphatase phosphorylation?
Involved in the last step
Transfers electrons at the last step in the production of cellular energy
How is Cytochrome C involved in the electron transport chain?
Cytochrome C is like a small cellular wire which electrons can flow through
Carries one electron per trip, each time binds to electron and moves across.
Electricity is the flow of electrons within a conductive mater, such as metal wire
Electricity powers many cellular processes
Electrons may be picked up from one particular place, then delivered where needed
How are electrons involved with breathing?
Electrons are from breakdown of sugar (Make ATP) and end up being attached to oxygen forming water. This the fate of oxygen we breathe and why we breathe.
Which electron carrier is used?
Heme group which is the prosthetic group
What is the job of the Heme group?
Pick up and transport electrons
What is the protein surrounding the Heme group used for?
Protein is like a scaffold, carrying the heme group
Can change the properties of the prosthetic group
Depending on its environment it will more or less except an electron, or donate differently
How does the Heme group attach the electron?
Ion attaches to electron and passes it on
The Ion coordinated to a porphyrin acting as a tetradentate ligand (N), and to one or two axial ligands (amino acids).
Where are the electrons gathered from?
From cytochrome bc1 complex and delivers to cytochrome oxidase complex
What are the structural features of cytochrome C proteins?
together
loop
100 AA’s (12kDa), high conserved in eukaryotes, differing by only a few residues
Alpha Helical fold
Functionally conserved
Contains characteristic CXXCH (cysteine-any-any-cysteine-histidine) AA’s motif that binds heme
How is Cytochrome C involved in Apoptosis?
CytoChrome C is released by mitochondria, in response to pro-apoptotic stimuli (Ca^2+ changes in BCL-2 protein expression, ROS etc).
Diffuses out to interact with proteins (InsP3 receptor, Caspase-9).
Further Ca2+ release stimulates more cytochrome c is released
Explain Apoptosis
Release of cytochrome c from mitochondria
binding to protein Apaf-1
Causing it to assemble into seven-fold-ring
Caspases, activated by binding to the ring of CARD domains on the assembled apoptosome
How is Apoptosis involved in development?
Normal development
Maintenance of tissues homeostasis
Effective immune system
Disturbance implicated in numerous pathological conditions ranging from degenerative disorders to autoimmunity to cancer
What are the characteristic biochemical changes in cells undergoing apoptosis?
1) Chromosomal DNA cleaved into fragments
2) Change in the plasma membrane, For example, Phosphatidylserine in outer leaflet
3) Loss of electrical potential across the inner membrane of the mitochondria
4) Relocation of cytochrome c from intermembrane space of mitochondria to cytosol
What are the symptoms of necrosis?
1) Cellular swelling
2) Membranes are broken
3) ATP is depleted
4) Cell lyses, eliciting an inflammatory reaction
5) DNA fragmentation random and smeared
6) Vivo, whole areas of the tissues are affected
What are the symptoms of Apoptosis?
1) Cellular condensation
2) Membranes remain intact
3) Requires ATP
4) Cell phagocytosed, no tissue reaction
5) Ladder-like DNA fragmentation
6) In vivo, individual cells appear affected
Explain the Apoptotic pathway: Extrinsic pathway
Death lings- Death receptors- Initiator caspase 8- Effect Caspase 3- Programmed cell death
Explain the Apoptotic pathway: Intrinsic pathway
DNA damage and p53- Mitochondria/Cytochrome C - initiator Caspase- Effect Caspase 3- Programmed Cell death
What are the inhibitors of Cytochrome C?
Cyanide and azide bind tightly to cytochrome oxidase complex, stopping electron transport, reducing overall ATP production.
How does the intrinsic pathway of apoptosis depend on the mitochondria?
Release of cytochrome C from mitochondrium
Binds to Apa1, activating Apaf1 with the help of hydrolysis of bound dATP to dADP
Apaf1 forms complex called Apoptosome by the release of dADP in exchange for dATP (or ATP)
Recruitment of other proteins such as procaspase-9 which is activated
The caspase-9 is cleaved, activating executioner procaspase
The caspase cascade is then activated leading to Apoptosis
How does pro-apoptotic BH3-only and Anti-apoptotic Bd2 proteins regulate the intrinsic pathway of apoptosis?
Regulates the release of proteins
Found in the mitochondria
How is Cytochrome C in relation to Apoptosome?
Cyt c binds apoptotic to peptidase starting factor Apaf-1
Recruits and activates procasepase-1
Caspase-9 activates other caspases
Caspases degrade proteins and active endonucleases
Give a brief rundown of the Cytochrome C conclave
Cytochrome c binds to Apaf-1 forming Caspase 9 -> Caspase 3 -> Apoptose substrate -> Cell death
Caspase 3 can also go of to form IAP,, which can produce Smac and omi
It can also go to caspases
