TCA And Oxidative Phosphorylation Flashcards
What does Pyruvate Dehydrogenase do?
Catalyses the conversion of pyruvate to acetyl CoA, producing CO2 and NADH
Where is Pyruvate Dehydrogenase found
Mitochondrial matrix
Why is Pyruvate Dehydrogenase sensitivity to a vitamin B1 deficiency
The enzyme activity requires cofactors and B vitamins provide these factors
True or false: the reaction catalysed by pyruvate dehydrogenase is reversible
False. It’s irreversible making it a key regulatory step
What activates pyruvate dehydrogenase
Pyruvate, CoA, NAD+, ADP and Insulin (low energy signals)
What inhibits Pyruvate Dehydrogenase
Acetyl CoA, NADH, ATP, citrate (high energy signals)
True or False: Pyruvate cannot be formed from acetyl-CoA
True, the loss of CO2 is irreversible
What does a deficiency in pyruvate dehydrogenase lead to
Lactic acidosis (increase in blood lactate levels)
Where does the TCA cycle occur
Mitochondrial matrix
What does TCA stand for
Tricarboxylic Acid cycle
Outline the Kreb’s cycle
- Acetyl CoA binds with the 4 carbon oxaloacetate to form the 6 carbon citrate
- citrate is converted into the 6 carbon isocitrate
- isocitrate dehydrogenase oxidises isocitrate causing the loss of CO2 and production of NADH
- alpha-ketoglutarate is oxidised by alpha-ketoglutarate dehydrogenase causing the loss of CO2 and production of NADH
- compound is modified releasing CoA and producing GTP
- FADH2 is produced
NADH produced to reform oxaloactetate
For 1 molecule of glucose what is produced in the TCA cycle
6 NADH
2 FADH2
2 GTP
What are isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase regulated by
High energy signals (ATP and NADH)
True of false: alpha-ketoglutarate dehydrogenase is inhibited by its product
True
How does the Kreb’s cycle allow for anabolic reactions
It supplies intermediates for biosynthetic processes
Give some example of interconversions allowed by the Kreb’s cycle
- citrate to fatty acids
- alpha-ketoglutarate into amino acids
- oxaloacetate into glucose and amino acids
Does the Kreb’s cycle occur in the absence of oxygen
No, as the NADH and FADH2 cant offload their hydrogen and so there are no free NAD+ and FAD to pick up hydrogen so the TCA stops
By the end of the Kreb’s cycle how much ATP has been produced per glucose
4 ATP
Where does oxidative phosphorylation occur
Inner mitochondrial membrane
What happens to NADH and FADH2 in oxidative phosphorylation
They are reoxidised
Outline the electron transport which occurs before oxidative phosphorylation
NADH and FADH2 offload their electrons through a series of protein translocating complexes. As the electrons are transferred through the chain to oxygen they release energy which move hydrogen across the membrane
Energy from what allows the Hydrogen ions to pass into the intermitochondrial space
Energy is released when the electrons are transferred through the protein carrier molecules
Why are the electrons transferred through more than one carrier molecule in steps
So that energy is contained and you have more control on the production so less energy is wasted
How many hydrogen ions travel through the membrane due to 1 molecule of NADH offloading it’s electron pair
6
How many hydrogen ions are transferred through the carrier molecules when 1 molecule of FADH2 offloads it’s electron pair
4
Why does NADH allow to movement of more hydrogen ions
It’s a higher energy molecule
What proportion of the energy released by the movement of electrons is used to pump hydrogen ions across the membrane
30% the rest is lost as heat
Why is a hydrogen ion gradient allowed to build up
The inner mitochondrial membrane is very impermeable so hydrogen ions can move through easily, they had to move through the carrier molecules
What is the proton motive force
The hydrogen ion gradient across the inner mitochondrial membrane
What does ATP synthase catalyse
The production of ATP from ADP + Pi as hydrogen ions flow through the enzymes down their electrochemical gradient
How many protein translocation complexes do NADH and FADH2 use
NADH -3
FADH2 -2
What happens if the proton motive force is increased
More ATP is synthesised
Oxidation of 2 moles of NADH and FADH2 produce how many moles of ATP
NADH- 5
FADH2 - 3
What happens to oxidative phosphorylation if ATP concentration is high
There is a low ADP concentration so there’s no substrate for ATP synthase so the inward flow of hydrogen ions stops and the H+ conc in the intermitochondrial space increases stopping the electron transport chain
What regulates electron transport and oxidative phophorylation
ATP concentrations
What does an inhibitor of oxidative phosphorylation do
Blocks the electron transport by preventing the acceptance of electrons by oxygen
Give an example of an oxidative phosphorylation inhibitor
Cyanide and carbon monoxide
What are uncouplers
Molecules that increase the permeability of the inner mitochondrial membrane to protons so dissipate the proton gradients reducing the proton motive force so there’s no drive for ATP synthesis
Give 3 examples of uncouplers
Fatty acids, dinitrophenol and dinitrocresol
What are oxidative phosphorylation diseases
Genetic defects in proteins encoded by mtDNA which lead to a decrease in electron transport and ATP synthesis
What naturally occurring uncoupling protein does brown adipose tissue contain
Thermogenin
How does brown adipose tissue produce extra heat
In response to the cold and noradrenaline lipase releases fatty acids from triacylglycerol and then go on to activate thermogenin (or is oxidised).
What does thermogenin do?
Transports H+ back into the mitochondria so the energy from the proton motive force is released as extra heat
What mechanism of ATP production is the major process in cells requiring large amounts of energy
Oxidative phosphorylation
Which mechanism for ATP production can occur in the absence of oxygen (to some extent)
Substrate level phosphorylation
How does energy coupling occur in substrate level phosphorylation
Directly through the formation of high energy from hydrolysis bonds (phosphoryl group transfer)
How does energy coupling occur in oxidative phosphorylation
Energy coupling occurs indirectly through generating and using the proton motive force
Where does substrate level phosphorylation take place
In the cytoplasm and mitochondrial matrix
What is the net yield of ATP from 1 molecule of glucose following the Kreb’s cycle (taking into account the NADH and FADH produced)
32
