Metabolism - TCA and ETC Flashcards
What does the TCA produce per glucose?
6NADH 2FADH 2GTP ------------ = 20ATP
Where does the TCA occur and what does it require?
Occurs in the mitochondria and is oxidative, so requires NAD+. It also requires O2
What does krebs provide in terms of metabolites?
Produces metabolites that can be used in biosynthesis processes
- oxaloacetate and citrate for FA transportation to cytoplasm for FA synthesis
- oxaloacetate and alphaketoglutarate for a/a transamination
How is the TCA regulated?
1) . Energy availability
- stimulated by low ATP to ADP ratio
- stimulated by low NADH to NAD+ ratio
- inhibited by high ATP to ADP ratio
- inhibited by high NADH to NAD+ ratio
2) . Isocitrate dehydrogenase converts isocitrate into alphaketoglutarate.
- When lots of krebs is occurring, citrate builds up and inhibits isocitrate dehydrogenase.
- Isocitrate dehydrogenase is also inhibited allosterically by NADH and stimulated allosterically by ADP.
2) .
Where does oxidative phosphorylation occur?
The mitochondria
What occurs in oxidative phosphorylation?
1). NADH in matrix passes its electrons to PTC1 (carriers in inner mitochondrial membrane), FAD2H starts at PTC2 as it is lower in energy.
2). Energy is released at each ‘jump’ the electron makes between carriers
= energy used to transfer H+ into the inner membrane space.
= some energy lost as heat
3). Electrons leave the carriers and are accepted by H+ and O2 to form water at the end.
4). A pmf has been established. It is now dissipated by ATP synthase, allowing the H+ to return to the matrix
= drives ADP + Pi ——> ATP
How is oxidative phosphorylation regulated?
1) . Inhibited by a high ATP to ADP ratio
- low ADP = no substrate for ATP synthase = pmf isn’t dissipated as much = inward flow stops = H+ conc builds up in the inner membrane space = ETC stops.
2). CO and CN- both bind to O2 with a high affinity
= no final acceptor for electrons at end of ETC = can’t continue down ETC = no pmf generated.
What do uncouplers do?
They increase the permeability of the inner mitochondrial membrane to H+ = pmf can be dissipated without driving ADP + Pi —-> ATP
= energy is lost as heat.
How does brown adipose tissue use uncouplers?
1). Noradrenaline is released as a response to the cold
= activates lipase = fatty acids are released.
2). Fatty acids activate UCP1 and undergo beta oxidation to obtain NADH which drives ETC
3). UCP1 transports H+ back into mitochondrial matrix after being pumped into inter membrane space = uncoupling of ETC and ATP synthesis (as H+ no longer has to drive ATPase)
= H+ dissipates and is captured as heat.
What is substrate level phosphorylation?
ADP + Pi —–> ATP
Compare and contrast substrate level phosphorylation and oxidative phosphorylation.
- OP requires a membrane associated complex (PTCs), SLP requires soluble enzymes only.
- OP energy coupling occurs by building and dissipation of a pmf, in SLP, it is via formation of a high energy bond by phophoryl group transfer.
- OP requires O2, whereas SLP can be anaerobic to an extent.
- OP is the major ATP synthesis route, SLP is minor.
