2. TCA cycle Flashcards
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?
- Electron transport chain
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.
What is UCP1?
Naturally occurring thermogenin uncoupling protein in brown adipose tissue.
Role in heat generation.
What age group have the most brown adipose tissue present?
Newborn infants
How do inhibitors and uncouplers differ?
With uncouplers electron transport continues but with heat production rather than ATP production whereas with inhibitors both the transport of electrons and ATP production stop.
What is the anabolic role of the TCA cycle?
Provide intermediates for the synthesis of various important molecules such as haem, fatty acids, glutamate and aspartate
How are superoxide radicals produced by mitochondria?
During oxidative phosphorylation about 0.1 - 2% of electrons do not reach the end of the electron transport chain and they prematurely reduce oxygen to from superoxide radicals (O2-).
What processes does the TCA cycle provide precursors for?
- Amino acid synthesis
- Haem synthesis
- Fatty acid synthesis
- Glucose synthesis
