Energy Production - TCA and ETC Flashcards
True or False:
Pyruvate enters directly into Stage 3 (TCA)
False - has to be converted into acetyl coA first
Which enzyme converts pyruvate into acetyl coA?
Pyruvate dehydrogenase
What is the equation for the conversion of pyruvate into acetyl coA?
CH3COCOOH + CoA + NAD+ –> CH3CO~CoA + CO2 + NADH + H+
Where does the conversion of pyruvate to acetyl coA occur?
Mitochondrial Matrix
As pyruvate dehydrogenase is a large multi-enzyme complex, how many enzymes does it consist of?
5
Why is the conversion of pyruvate to acetyl coA sensitive to Vitamin B1 deficiency?
The different enzyme activities require various cofactors (FAD, thiamine pyrophosphate and lipoid acid) which are provided by B-vitamins
Why is the link reaction a key regulatory step?
It is irreversible - rate limiting
What does pyruvate dehydrogenase deficiency cause?
Lactic acidosis
What is pyruvate dehydrogenase activated by?
Pyruvate, CoA, NAD+, ADP and Insulin
What is pyruvate dehydrogenase inhibited by?
Acetyl-CoA, NADH, ATP, citrate
Where does the Kreb’s cycle occur?
Mitochondria
What are some feature of the Kreb’s cycle?
Single pathway
Acetyl converted to 2CO2
Oxidative (requires NAD+, FAD)
Some energy is produced as ATP and GTP
Produces some precursors for biosynthesis
How many cycles of TCA are there per glucose entering glycolysis?
Two
What does acetyl coA join with to form citrate (C6)?
Oxaloacetate (C4)
How many carbons does isocitrate have?
6
What is also produced from the production of a-ketoglutarate (C5) from isocitrate (C6)?
NADH and CO2
The C5 molecule a-ketoglutarate combines with CoA to produce succinyl-CoA (C4). What is also produced?
CO2 and NADH
What is produced when succinyl-CoA is converted into succinate?
GTP from GDP
What is produced when succinate is converted into fumerate?
FADH2
How is oxaloacetate produced?
Oxidation of malate (C4) - also converts NAD+ into NADH
How many NADH, FADH2 and GTP molecules are produced per glucose from TCA?
6 NADH
2 FADH2
2 GTP
How is TCA cycle regulated?
By energy availability i.e. ATP/ADP ratio and NADH/NAD+ ratio
Does TCA cycle function in the absence of O2?
No
What is stage 4 of catabolism and where does it occur?
Electron transport chain - occurs in mitochondria
What happens to NADH and FADH2 in the ETC?
Reoxidised
Which type of phosphorylation occurs in the ETC?
Oxidative phosphorylation
What happens to electrons in the ETC?
They are transferred through a series of carrier molecules with increasing electronegativity to O2 - the final electron acceptor
What is the role of H+ ions in the ETC?
Energy used to move H+ across membrane (a lot of energy released as heat) - H+ gradient established across inner mitochondrial membrane = proton motive force
What is the only way in which protons can return across the mitochondrial membrane?
Via ATP synthase - driving ATP synthesis
Why does NADH use 3 PTCs while FADH2 only uses 2?
Electrons in NADH have more energy than in FADH2
How many moles of ATP are synthesised per oxidation of 2 moles of NADH?
5 moles of ATP
How many moles of ATP are synthesised per oxidation of 2 moles of FADH2?
3 moles of ATP
How is oxidative phosphorylation regulated?
Eg
When [ATP] is high, no substrate for ATP synthase as [ADP] is low
Inward flow of H+ therefore stops
Concentration of H+ in intermitochondrial space increases
This prevents further H+ pumping - stops electron transport
What is an example of an inhibitor of electron transport?
Cyanide - prevents acceptance of electrons by oxygen
What do uncouplers do?
Increase the permeability of the mitochondrial inner membrane to protons
Dissipate the proton gradient, thereby reducing the proton motive force - no drive for ATP synthesis
What are some examples of uncouplers?
Dinitrophenol, dinitrocresol, fatty acids
What are Ox/Phos diseases?
Genetic defects in proteins encoded by mtDNA - decreases in electron transport and ATP synthesis
In brown adipose tissue, what is the degree of coupling controlled by?
Fatty acids (uncouplers) - allows extra heat generation
What naturally occurring uncoupling protein does brown adipose tissue contain?
Thermogenesis (UCP1)
In brown adipose tissue, in response to cold, what does noradrenaline activate?
- Lipase which releases fatty acids from triacylglycerol
- Fatty acid oxidation -> NADH/FADH2 -> electron transport
Fatty acids activate UCP1
UCP1 transports H+ back into mitochondria
So electron transport uncoupled from ATP synthesis meaning energy of PDF is then released as extra heat
What is brown adipose tissue found in?
Newborn infants to maintain heat and hibernating animals to generate heat to maintain body temperature
How many moles of ATP are produced per mole of glucose in respiration?
32 moles
