MCB 2000 Lecture Notes - Lecture 22: Oxidative Decarboxylation, Acetyl-Coa, Lipoamide
16 May 2018
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Lecture 22
Pyruvate Dehydrogenase Reaction
Pyruvate Dehydrogenase Complex (PDC)
● Very important enzyme in metabolism
● not part of glycolysis or TCA cycle; but the connecting link
● Located in Matrix of Mitochondria
○ Is a large complex
○ Structure is determined in the early 2000s
Structure Pictures
● E1: Pyruvate Dehydrogenase, Quaternary structure (2 Alpha 2 Beta)
● E2: Transacetylase (3 Alpha)
● E3: Dihydrolipoyl Dehydrogenase (Alpha Beta)
○ Don’t need to know proper names but know which rxns they catalyze
● Type of rxn is Oxidative Decarboxylation: Loss of CO2 & an oxidation/reduction rxn
○ What is oxidation/reduction
■ Oxidation: Loss of E, NADH → NAD+
■ Reduction: Gain of E, NAD+ → NADH
● Think of an “electron” as being an H
○ Forms 2 Carbon Molecule Acetyl CoA & capture elections as NADH
■ Essentially creates a very important molecule (acetyl Coa) ; also captures
electrons in form of NADH
○ 2 types of vitamins used
PDC uses several coenzymes for its catalytic mechanism
● Vitamin Coenzymes - catalytic, covalently bound (if they take part in the chemistry they must be
reset to their original chemical state, they are used repeatedly)
○ Thiamine Pyrophosphate (TPP) - B vitamin
○ Lipoic Acid
○ Flavin Adenine Dinucleotide (FAD/FADH2) - is covalently bound, carries out oxidation
reduction
● Vitamin Coenzymes - stoichiometric, not bound (come on and off the enzyme, not reset by the
enzyme )
○ CoA
○ NAD+
3 Step Rxn
1. Pyruvate (3C) will lose a CO2 → decarboxylation
2. Next, 2 e- come off → oxidation
3. Remainder is transferred to CoA → product is acetyl CoA
- *there is a thioester covalent bond (high energy
)
- Irreversible, only goes in one direction
Mechanism of Steps: Step 1
● Step 1 → decarboxylation of pyruvate
○ Carbanion + Pyruvate = Hydroxyethyl-TPP + CO2
○ E1
● Step 2 → oxidation & transfer
○ Hydroxyethyl form loses proton + Lipoamide = Carbanion TPP + Acetyl Lipoamide
○ E1
○ Acetyl group forms + transferred to lipoamide (lipoamide is bound to E2)
Document Summary
Not part of glycolysis or tca cycle; but the connecting link. Structure is determined in the early 2000s. E1: pyruvate dehydrogenase, quaternary structure (2 alpha 2 beta) Don"t need to know proper names but know which rxns they catalyze. Type of rxn is oxidative decarboxylation: loss of co2 & an oxidation/reduction rxn. Oxidation: loss of e, nadh nad+ Reduction: gain of e, nad+ nadh. Think of an electron as being an h. Forms 2 carbon molecule acetyl coa & capture elections as nadh. Essentially creates a very important molecule (acetyl coa) ; also captures electrons in form of nadh. Pdc uses several coenzymes for its catalytic mechanism. Vitamin coenzymes - catalytic, covalently bound (if they take part in the chemistry they must be reset to their original chemical state, they are used repeatedly) Flavin adenine dinucleotide (fad/fadh2) - is covalently bound, carries out oxidation.
