MCB 2000 Lecture Notes - Lecture 23: Pyruvate Dehydrogenase Complex, Acetyl-Coa, Pyruvate Dehydrogenase
16 May 2018
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Lecture 23 & 24
TCA Cycle
Outline
● TCA Cycle produces → 2 ATP, NADH & FADH
○ Main purpose is to capture all 8 electrons from acetyl CoA
○ ***** Should know how many NADH and FADH are produced
○ Also has anabolic functions, intermediates of TCA cycle are used for biosynthesis
○ Isomerizations
○ Thioester bonds
● All nutrients, fats, proteins, fatty acids → all these C skeletons give acetyl CoA
Overview of TCA cycle
○ First: oxidize Acetyl CoA + release CO2
○ Produces & delivers reducing equivalents (NADH) to the ETC
○ Regenerates OAA
○ Generates high energy GTP or ATP
○ Has two phases
■ Capture of e- by oxidizing the Cs of acetyl CoA
● Thioester bond: can be used in 2 ways
● Related to pyruvate dehydrogenase complex
● Links the 2 Cs from pyruvate to the CoA molecule
○ The CoA is what has the SH group
○ When linked to the 2Cs in the Pyruvate Dehydrogenase rxn,
forms the thioester bond
■ Regeneration of Oxaloacetate (OAA) - 4C molecule
TCA Cycle Chemistry
● Seems complicated way to oxidize acetate to CO2
○ Normal C-C cleaving bonds don’t work for acetyl-coA
○ Need to condense acetate w/ oxaloacetate + then carry out a beta-cleavage
○ TCA cycle combines this with oxidation to form Co2, regenerate oxaloacetate, capture all
energy as NADH & ATP
● Majority of Enzymes in TCA cycle all have a unique characteristic that they contribute to the cycle
Citrate Synthase
● Use 2 substrates: OAA & acetyl CoA (Condensation rxn)
○But it matters which substrate binds first
○ OAA must bind first, when it binds then conformation of enzyme changes
■ Creates the binding site for acetyl CoA
■ In absence of OAA, there is no binding site for acetyl CoA
○ Condensation rxn: linking 2 molecules together to form an intermediate
■ Split off a thioester bond, lots of energy released
■ Hydrolysis of thioester bond during condensation rxn to drive TCA cycle in the
forward direction
Coupled Rxns 1
● OAA is immediately used after its produced by citrate synthase
Document Summary
Tca cycle produces 2 atp, nadh & fadh. Main purpose is to capture all 8 electrons from acetyl coa. ***** should know how many nadh and fadh are produced. Also has anabolic functions, intermediates of tca cycle are used for biosynthesis. All nutrients, fats, proteins, fatty acids all these c skeletons give acetyl coa. First: oxidize acetyl coa + release co2. Produces & delivers reducing equivalents (nadh) to the etc. Capture of e- by oxidizing the cs of acetyl coa. Thioester bond: can be used in 2 ways. Links the 2 cs from pyruvate to the coa molecule. The coa is what has the sh group. When linked to the 2cs in the pyruvate dehydrogenase rxn, Regeneration of oxaloacetate (oaa) - 4c molecule forms the thioester bond. Seems complicated way to oxidize acetate to co2. Normal c-c cleaving bonds don"t work for acetyl-coa. Need to condense acetate w/ oxaloacetate + then carry out a beta-cleavage.
