Electron Transport Chain Flashcards
What does glycolysis produce?
- 2 ATP
- Pyruvate
- 2 NADH
How many molecules of NADH are made from a single Acetyl CoA molecule?
3 NADH (from 1 pyruvate)
What is produced from one Acetyl CoA molecule?
- 3x NADH
- FADH2
- GTP
How many molecules of NADH are involved in the ETC?
8 overall
- 2 NADH from glycolysis
- 3 NADH from 1st Acetyl CoA
- 3 NADH from 2nd Acetyl CoA
How are the 2 molecules of NADH produced from glycolysis transfered into the mitochondria?
Malate shuttle
NADH transfers its electrons to OAA to make malate (then becomes NAD+)
Malate crosses mitochndrial membrane then is transfered into OAA (with NAD+ becoming NADH)
What is oxaloacetate converted into which can then allow it to cross the mitochondrial membrane?
Aspartate (via Glut -> a-KG)
What is aspartate converted back into in the cytosol after crossing the mitochondrial membrane?
OAA (via a-KG -> Glut)
What enzyme converts Dihydroxyacetone phosphate to Glycerol Phosphate (via NADH -> NAD+), donation of electron?
Glycerol Phosphate Dehydrogenase
What does the mitochondrial membrane version of Glycerol Phosphate Dehydrogenase do?
Converts Glycerol phosphate back into Dihydroxyacetone phosphate
- FAD -> FADH2
What does membranous Glycerol Phosphate Dehydrogenase produce / convert other than Dihydroxyacetone phosphate?
FADH2 (from FAD)
What is the disadvantage of the glycerol phosphate shuttle in comparison with the malate shuttle?
FADH2 (glycerol phosphate shuttle) cannot produce as many ATPs as NADH (which is produced from malate shuttle)
How does ETC generate energy?
Throigh extracting electrons from NADH and FADH2 to oxygen and in the process then generating energy (and water)
What is complex I also known as?
NADH Dehydrogenase
What does NADH dehydrogenase (complex I) do?
- Oxidises NADH (NADH -> NAD+)
- Transfers electrons (from NADH) to coenzyme Q (ubiquinone)
What is coenzyme Q also known as?
ubiquinone
What does CoQ shuttle electrons to?
Complex III
Where are the Electron transport complexes found?
On the inner membrane of the mitochondria
What is pumped into the inner membrane space by complex I?
H+ (later used to produce ATP)
What are CoQ10 supplements taken in conjunction with and why?
Statins
- Statins are thought to decrease CoQ levels
- No good data to support this
What is Complex II also known as?
Succinate dehydrogenase (TCA cycle)
How many electron transport complexes are there?
4
What are some of the key intermeadites of complex I?
- Flavin mononucleotide
- Iron sulfur compounds (FeS)
What does Complex II (Succinate dehydrogenase) transfer electrons to?
From Succinate (becomes fumarate)
- To FADH2
- Then to CoQ
What does succinate become as a result of complex II?
Fumarate
What is complex III also known as?
Cytochrome bc1 complex
What are the roles of complex III?
- Transfers electrons CoQ -> cytochrome c
- Pumps H+ to intermembrane space
What does cytochrome C pass the electrons to?
Complex 4
Where is cytochrome c found?
Inner membrane space
Where are all the complexes found?
On the inner membrane of the mitochondria
What are cytochromes made of?
Class of proteins:
- Contain a heme group
- Iron plus porphyrin ring
What is the makeup of the iron in Hgb in comparison with cytochromes?
- Hgb: Mostly Fe2+
- Cytochromes: Fe2+ or Fe3+ (goes back and forth)
Why does cytochromes changing between Fe2+ and Fe3+ benefit electron transport?
Means oxidation state can change with electron transport (can donate electrons)
What are cytochromes a b and c used in?
Electron transport
What is cytochrome P450 used in?
Drug metabolism
What are other names for complex IV?
- Cytochrome a + a3
- Cytochrome c oxidase (reacts with O2)
What element does complex IV contain?
Copper (Cu)
What does complex IV do?
- Pumps H+
- Combines electrons that have come at it from the other elements of the ETC with O2 to generate water
What are the 2 ways to produce ATP?
- Substrate level phsophoryation (via an enzyme)
- Oxidative phosphorylation
Where is the only place where oxidative phosphorylation can occur?
Mitochondria
What enzyme leaks H+ ions out of the inner membrane space?
ATP Synthase
How does ATP Synthase create ATP?
H+ ions from inner membrane space travel across and are energy rich so can convert ADP to ATP
- Converts proton charge gradient -> ATP
What is another name for ATP synthase?
Complex 5
What is the process by which protons move down the gradient?
Chemiosmosis
- Uses electrochemical gradient
- Known as a proton motive force
What is the P/O ratio?
Amount of ATP generated per molecule of O2
What is the P/O ratio for NADH and FADH2?
- 2.5 - 3 per NADH
- 1.5 - 2 per FADH2
How can the 2NADHs produced from glycolysis produce ATP?
Malate shuttle -> 2 NADH (6 ATP)
Glycerol-3-Pi shuttle -> 2 FADH2 (4 ATP)
How many ATPs can be produced from GTP?
1
How may molcules of ATP are roughly made from one molecule of Acetyl-CoA?
12 ATP
- 3 NADH -> 9 ATP
- 1 FADH2 -> 2 ATP
- 1 GTP -> 1 ATP
How many molecules of ATP are made per glucose?
30 / 32 molecules (depending on whether malate or glycerol-3-Pi shuttle is used for the 2 NADH from glycolysis)
What are the 2 main ways by which drugs/poisons can disrupt oxidative phsophorylation?
- Block/inhibit electron transport
- Allow H+ to leak out of inner membrane space (‘uncoupling of electron trnasport / oxidative phosphorylation)
How does rotenone (insecticide) disrupt the ETC?
- Binds to complex I, preventing electron transfer (reduction) to CoQ
How does Antimycin A (antibiotic) disrupt the ETC?
- Binds to complex III (bc1 complex)
What 2 substances bind to complex IV?
- Carbon monoxide (binds to a3 in Fe2+ state - competes with O2)
- Cyanide (bind a3 in Fe3+ state)
What does cyanide bind to?
Complex IV
- a3 in Fe3+ state
- RBCs not affected as not in Fe3+ state mostly
What does CO bind to?
Complex IV
- a3 in Fe2+ state
- Competes with O2
What are the symptoms of cyanide poisoning?
- Headaches, confusion
- Tachycardia, hypertension
- Tachypnea
- Bright red venous blood (due to increased O2 content)
- Almond smell
- Lactic acidosis (anaerobic metabolism)
What substance may cuase cyanide poisoning?
What is it used for?
Nitroprusside
- Treatment of hypertnesive emergencies
- Toxic levels woth prolonged infusions
- Contains 5 cyanide groups per molecule
How can cyanide / nitroprusside poisoning be treated?
Nitrites (amyl nitrite)
How do nitrites (amyl nitrite) work?
- Converts Fe2+ -> Fe3+ in Hgb (methemoglobin)
- Fe3+ in Hgb binds cyanide, protect mitochondria
What do uncoupling agents do?
Pierce the inner membrane, making holes so H+ molecules leak out, meaning they cannot be utilised by ATP synthase
What are examples of uncoupling agents (allow H+ to leak out of inner membrane space)?
- 2,4 dinitrophenol (DNP) (weight loss med)
- Aspirin (overdoes)
- Brown fat
What is a mjor sign of aspirin overdose (uncoupling agents)?
Fever
- Uncoupled oxidative phosphorylation
- H+ ions leaking out generate heat
What substance does brown fat (found in newborns and hibernating animals) contain which gives it uncoupling capabilities?
Uncoupling protein 1 (UCP-1, thermoegenin)
How does Uncoupling protein 1 (UCP-1, thermoegenin), found in brown fat, work?
Sympathetic stimulation (NE, B receptors) leads to lipolysis, does not generate ATP as: - Electron transport does not work properly, ATP not produced, instead H+ ions released, generating heat
How can Oligomycin A affect the ETC?
- Inhibits ATP synthase
- H+ cannot move through enzyme
- Trapped
- Oxidative phosphprylation stops
- ATP not generated
What is oligomycin A?
Macrolide antiB not used clinically