TCA Cycle/OXPHOS Flashcards
3 Products of TCA Cycle (& ATP that comes from them) per acetyl-CoA oxidized
3 NADH - 9 ATP
1 FADH2 - 2 ATP
1 GTP - 1 ATP
5 Steps in PDH Complex
Pyruvate decarboxylase ejects CO2 from pyruvate and binds it to TPP
Dihydrodrolipoyl transacetylase moves it to oxidized lipoamide
Acetyl group then transferred to CoA to form acetyl CoA
The sulfhydryl (reduced) lipoamide oxidized back to form via FAD-dependent dihydrolipoyl dehydrogenase
FADH2 reoxidized to FAD by dihydrolipoyl dehydrogenase by reducing NAD+
5 Vitamins/Coenzymes Associated w/ PDH Complex
TPP Lipoic Acid CoA FAD NAD
Regulation of PDH Complex (2)
PDH Kinase phosphos and inactivates it, while PDH phosphatase activates it
3 Activators/1 Inhibitor of PDH Kinase
A: ATP, acetyl-CoA, and NADH (so shut off PDH complex when have high energy)
I: Pyruvate
Activator of PDH Phosphatase
Ca++
1st Step of TCA Cycle
Citrate synthase joins acetyl-CoA and oxaloacetate to citrate, consuming water and expelling CoA
1st Irreversible step
2nd Step of TCA Cycle
Aconitase isomerizes citrate to isocitrate
3rd Step of TCA Cycle
Isocitrate dehydrogenase converts isocitrate to alpha-ketoglutarate
1st NADH producing step
1st CO2 expelling step
2nd irreversible step
2 Activators/2 Inhibitors of Isocitrate dehydrogenase
I: ATP/NADH
A: ADP/Ca++
4th Step of TCA Cycle
alpha-Ketoglutarate dehydrogenase complex converts alpha-ketoglutarate to succinyl-CoA 2nd energy producing step, NADH 2nd CO2 expelling step Consumes CoA 3rd irreversible step
alpha-Ketoglurate dehydrogenase complex (activator, 2 inhibitors, comparison)
Almost identical to PDH complex, including 5 coenzymes (TPP, lipoamide, CoA, FAD, NAD)
A: Ca++
I: NADH, succinyl-CoA
5th Step of TCA Cycle
Succinate thiokinase converts succinyl-CoA to succinate
Uses substrate-level phosphorylation to create GTP from inorganic phosphate (VERY uphill)
Expels CoA
6th Step of TCA Cycle
Succinate dehydrogenase oxidizes succinate to create a double bond to form fumarate
Produces FADH2
7th Step of TCA Cycle
Fumarase adds across fumarate double bond to convert it to L-Malate
8th Step of TCA Cycle
Malate dehydrogenase converts L-Malate to Oxaloacetate
Generates 3rd NADH
4 Oxidation Reactions of TCA Cycle
Isocitrate, alphaketoglutarate, and malate dehydrogenase - NADH each
Succinate dehydrogenase - FADH2
Substrate-level Phosphorylation Reaction of TCA Cycle
Succinate thiokinase creates GTP from GDP + inorganic phosphate
3 Irreversible Reactions of TCA Cycle
Citrate synthase
Isocitrate dehydrogenase
alpha-ketoglutarate dehydrogenase complex
4 AA Entry Points in TCA Cycle (& reason)
alpha-ketoglutarate Succinyl-CoA Fumarate Oxaloacetate Enter to go to gluconeogenesis if starving
Complex I
NADH Dehydrogenase, forms FMNH2 from FMN via NADH + H+
Complex II
Succinate dehydrogenase, forms FADH2 from FAD via conversion of succinate into fumarate
CoQ
e- acceptor b/w Complexes I/II and III, accepts from FMNH2 and FADH2 to form CoQH2
Complex III
Cytochrome bc1, Fe3+ that accepts reduction to Fe2+
Cytochrome C
B/w III and IV, Fe3+ reduced to Fe2+ again
Complex IV
Cytochrome c oxidase, Fe3+ to Fe2+ again but then uses it to convert 1/2O2 to H2O
Energetic Coupling of OXPHOS (2)
As you go through the chain, the compounds become better oxidizing agents (accepting e-s); the E0 goes from negative to positive
H+ Pumps
Complexes I, III, and IV change shape as e-s pass through, pumping H+ from matrix to IM space
Difference in NADH/FADH2 ATP # Generation
NADH starts oxphos at Complex I so it hits all 3 pumps (and forms 3 ATP per), FADH2 enters at Complex II so only gets proton pumps from III and IV (and thus 2 ATP per)
Uncoupled Protons
Proton leaks uncoupled from ATP synthase allows protons to reenter matrix w/out capturing energy as ATP, generates heat