TCA cycle & ETC Flashcards
Relate the TCA cycle and oxidative phosphorylation to the overall map of metabolism and discuss its relevance.
- It’s the final common pathway for the catabolism of carbohydrates, amino acids & fatty-acids.
- It’s responsible for the bulk of ATP production in oxidative metabolism.
- Acts as a reservoir of chemical intermediates for anabolic metabolism.
Relevance:
- Generation of one molecule GTP (energy) as well as NADH and FADH2 which can be used to make ATP in e- transport chain.
Describe the TCA cycle reaction sequence and the sub-cellular location of the enzymes involved.
A cyclic pathway of 8 reactions:
Identify the steps at which chemical energy is captured.
In the presence of oxygen, 1 glucose molecule can produce a max of 30-32 ATP.
- Net 2 ATP and 2 NADH + H in glycolysis.
- 2 NADH + H in pyruvate oxidation.
- 2 ATP in, 6 NADH + H, 2 FADH2 in TCA cycle.
Identify the steps at which regulatory processes occur in the TCA cycle.
The TCA Cycle is regulated at three key points:
- Citrate Synthase
- Isocitrate Dehydrogenase (rate limiting step)
- a- Ketoglutarate Dehydrogenase
Activators: ADP & Ca2+
Inhibitors: ATP, GTP, NADH, Succinyl-CoA
Outline the energy yield (as ATP) from the catabolism of glucose under aerobic and anaerobic conditions.
In anaerobic conditions, pyruvate converts to lactate through anaerobic glycolysis. Anaerobic respiration results in the production of 2 ATP molecules.
Aerobic respiration:
Discuss chemiosmotic theory and the coupling of the electron transport chain to ATP synthesis
- The chemiosmotic theory involves the transfer of protons across an electrochemical gradient to generate ATP.
- This occurs within the ETC and is the final common pathway for NADH and FADH2 produced in catabolism and the TCA cycle.
- The ETC is tightly coupled to the process of oxidative phosphorylation via the ATP synthesis system for the production of useful energy for metabolism in the form of ATP. These processes are present in all mitochondria.
What is oxidative phosphorylation?
- Oxidative phosphorylation the process by which ADP is phosphorylated to ATP via the movement of electrons through the mitochondrial ETC and the associated consumption of oxygen to form H2O.
Where does ETC take place?
- ETC happens in the inner mitochondrial membrane (where ETC proteins are).
- NADH are transported here via substrate shuttles.
What are the two substrate shuttles that carry electrons into the inner mitochondrial membranes.
- Glycerol 3-phosphate (via glycerophsophate dehydrogenase)
- Malate-aspartate (via malate dehydrogenase)
Which shuttle produces more ATP?
Malate-aspartate (1 NADH oxidised and 1 NADH reduced = 3 ATP)
*Glycerol 3-phosphate 1 NADH oxidised to 1 FADH2 reduced = 2 x ATP
How many complexes are in the ETC?
4 complexes (I to IV): Each complex accepts & donates e-’s to mobile carriers
And ATP synthase
What are carriers of the ETC?
- They receive and donate e-.
- Cytochrome C and CoQ.
List the ETC multi protein complexes.
- NADH-Q reductase complex (Fe-sulphur centre)
- Succinate dehydrogenase complex: FADH2 & CoQ
- Cytochrome C reductase complex: (Cytochrome (Fe ion) centre for e- transport)
- Cytochrome C oxidase: copper and cytochrome e- carriers.
How does ATP synthase produce ATP?
- Free Energy released as electrons passed from complex to complex.
- This is used to pump H+ across the membrane thereby generating a membrane potential.
- H+ move back to the mitochondrial matrix through specific proton channel (found in Complex V: Fo unit)
- H+ passage through F0 causes rotation.
- F0 rotation= conformational change F1 allowing binding of ADP + Pi (ATP)
What is uncoupling?
- The breakdown of the gradient due to a membrane leakage or damage.
- This happens via:
1. Uncoupling proteins (proton leak, heat energy production in brown adipose tissue)
2. Synthetic uncouplers (Aspirin overdose + salicylates = no ATP synthase, heat energy release & fever)
3. Endogenous uncouplers (Free FA & bilirubin at ^ conc. = jaundice + brain damage in infants)
