What enzyme converts pyruvate to Acetyl CoA?
Pyruvate dydrogenase
Which vitamin deficiency affects PDH?
Vitamin B1 - cofactors
What molecules activate PDH?
Pyruvate NAD+ ADP Insulin = low energy signals
How is PDH activated?
Dephosophorylated
How is PDH inactivated?
Phosphorylated
What molecules inhibit PDH activity?
Citrate
ATP
NADH
Acetyl CoA
What will happen if there is PDH deficiency?
Pyruvate built up, NAD+ restored by conversion to lactate…lactic acidosis
Where does the TCA cycle happen?
Mitochondria
What are the 2 key rate-limiting enzymes in the TCA cycle?
isocitrate dehydrogenase
alpha-ketoglutarate dehydrogenase
What is the net production of NADH, GTP and FADH2 from one glucose in the TCA cycle?
6 NADH
2 FADH2
2 GTP
(2 Acetyl CoA per glucose)
Does the TCA cycle happen in absence of O2?
No, as no NAD+ and FAD
By what process are ATP and GTP synthesised in glycolysis and TCA cycle?
substrate- level phosphorylation
Where does the electron transport chain happen?
Inner mitochondrial membrane
What 2 processes are there in stage 4 of carbohydrate metabolism?
2. Oxidative phosphorylation
How many protein translocating complexes are there in the ETC?
3
Which PTC do NADH and FADH2 feed into?
NADH -1
FADH2 -2 as it has less energy so only pumps 4H+ across
What is the final electron acceptor?
O2 - becomes H20
What is the function of pumping hydrogen ions into the inter membrane space?
Hydrogen gradient is established - proton motive force which is used to synthesise ATP
How is ATP synthase regulated?
When [ATP] is high, there is no ADP substrate.
Inward flow of H+ stops and [H+] in intermembrane space increases, preventing electron transport.
Reverses with ADP available.
How does cyanide affect electron transport?
Inhibitor of complex IV (cytochrome c).
Prevents acceptance of electrons by O2, the electon transport chain stops and the proton motive force driving ATP synthesis fails
What do uncouplers do?
Increase the permeability of the mitochondrial inner membrane to protons.
Protons bypass ATP synthase. Thus, instead of being converted to ATP, the energy from the electron transport chain is released as heat.
What are examples of uncouplers?
Fatty acids
Dinitrophenol
Efficiency of oxidative phosphorylation depends on what?
Tightness of coupling (impermeability of IMM)
How does brown adipose tissue carry out thermogenesis?
In response to cold, NA activates lipase which releases FA from TAG.
FA are oxidised to produce NADH and FADH2 which enter ETC.
FA activates UCP1 to uncouple ETC.
Energy of pmf is released as heat.