Lecture notes 2

first the e1 bound tpp related to vitamin b1 absence

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Unformatted text preview: 2 ­ + NAD+ + CoA ­SH  ­> CH3 ­CO ­S ­CoA + NADH + CO2 –  ΔGo’ =  ­ 8 kcal/mole •  Catalyzed by pyruvate dehydrogenase complex –  E1 (24 α2β2 tetramers), E2 (8 α3 trimers ), and E3 (6 αβ dimers) •  “Stoichiometric” cofactors –  NAD+ –  CoA ­SH •  “CatalyFc” cofactors –  Thiamine pyrophosphate –  Lipoic Acid (fajy acid) –  FAD How it starts... •  First the E1 bound TPP (related to vitamin B1, absence of which causes beriberi) …does some carbanion chemistry on pyruvate... … and now the “aldehyde” gets oxidized by running into oxidized lipoate on E2... “AcFve aldehyde” …and then the dramaFc wrap ­up is trapped by the CoA This thioester While the electrons from substrate stay with the lipoamide and ... ….go first to a bound FAD ….and finally end up in a NADH mobile e ­ carrier The components of which can be broken down into... •  THE ENZYMES: •  E1: pyruvate dehydrogenase •  E2: Dihydrolipoyl transacetylase •  E3: Dihydrolipoyl dehydrogenase All of which occurs in a factory which is enormous... •  Located in the matrix of the mitochondrion and larger than ribosomes Blueprint of the factory... * E2’s assemble to form the octameric core : [(E2)3]8 * E1’s assemble in a dimeric way on each of the twelve edges of the cube...
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