TCA cycle Flashcards
What are the three main things to follow when going through the TCA cycle rxns?
-# of carbons and where they are
-movement of electrons
-follow the energy (delta G)
How many reactions are there in TCA cycle?
8 reactions
What is the output from 1 acetyl-CoA?
-2 CO2
-1 ATP
-3NADH/H+
-1 FADH2
Roughly how much ATP is 1 NADH equivalent to?
~2.5 ATP = 1 NADH
roughly how much ATP is 1 FADH equivalent to?
~1.5 ATP = 1 FADH
What is a metabolon?
-group of enzymes performing reactions with a common function
-these enzymes can be localized in organelle or part of organelle
-seen in glycolysis, gluconeogen, FA synth, and ETC
What is substrate channeling?
-when the product of one rxn directly becomes the substrate for the next rxn
-used for small molecules (1-2C)
-uses biological tethers
-ex. Co-A in acetyl-CoA
What is important about Acetyl-CoA?
-important intermediate
-product of pyruvate oxidation
-product of fatty acid metabolism
-chemical bonds are energetically rich
-carries 2C acetyl group
Step 1: citrate synthase
-condensation synthesis
-acetyl-coA (2C) + oxaloacetate (4C) -> citrate (6C)
-irreversible
-favourable rxn
Step 2: Aconitase
-isomerization (sort of) = two steps of dehydration then hydration
-citrate (6C) -> isocitrate (6C)
-reversible
-near 0 G
What is the intermediate for the two step reaction of aconitase enzyme?
cis-Aconitate
Step 3: Isocitrate Dehydrogenase
-oxidation decarboxylation
-isocitrate (6C)-> a-ketoglutarate (5C) + CO2
-produces NADH/H+
-irreversible
-favourable rxn
Step 4: a-ketoglutarate dehydrogenase
-oxidation decarboxylation
-a-ketoglutarate (5) -> succinyl-CoA (4) + CO2
-NADH/H+ produced
-irreversible -> Rate Limiting
-very favourable reaction
What are the parts of the a-ketoglutarate dehydrogenase complex?
-multienzyme
-E1 = TPP decarboxylase
-E2 = dihydrolipoyl transferase
-E3 = dihidyrolipoyl dehydrogenase
Of the carbons lost in the first 4 steps of TCA, are they from the acetyl CoA or the oxaloacetate?
-they are from the oxaloacetate
-still have both C from the acetyl CoA
Step 5: Succinyl CoA Synthase
-substrate-level phosphorylation
-succinyl-CoA (4C) -> succinate (4)
-1 ATP produced via water
-reversible rxn
-near 0 G
Step 6: Succinate Dehydrogenase
-oxidation
-succinate -> fumarate
-produces an FADH2
-reversible
-near 0 G
What is fumarate?
a trans-dioic acid
What is important about succinate dehydrogenase enzyme?
-bound to mito inner membrane
-part of Complex 2 in ETC
-near equilibrium = reversible
-FAD covalently bound
-uses FADH2 to reduce alkane to alkene because potential too low for NAD+
Step 7: Fumarase
-hydration
-fumarate (4C) + water -> malate (4C)
- reversible
-energy not used or produced
-near 0 G
Step 8: Malate Dehydrogenase
-oxidation
-Malate (4C) -> oxaloacetate (4C)
-reversible
-makes NADH/H+
-near 0 G = driven forward by product removal
Which steps of TCA are irreversible?
step 1, 3, 4
Which steps of TCA are reversible?
steps 2, 5, 6, 7, 8
Which steps produce NADH?
steps 3, 4, 8
Which step produces ATP?
step 5
What step produces FADH2?
step 6
What is an anaplerotic rxn?
rxns that replenish levels of TCA intermediates
What does NADH inhibit?
all three dehydrogenases
name 3 allosteric regulators in TCA regulation
-ATP
-Ca2+
-Succinyl CoA
What is regulation based on in TCA?
-substrate availability
What are the fates of the carbon atoms removed from TCA?
CO2
What are the fate of the electrons removed from TCA?
mostly NADH (some ATP and FADH2)
What are reducing equivalents?
-chemical species which transfer the equivalent of one electron in redox reactions
-NADH is a key carrier
