Pyruvate E pyruvate dehydrogenase CH3-C—C E, dihydrolipoyl transacetylase oxidized Eg dihydrolipoyl dehydrogenase Ipoynyslne HC-H TPP FAD TPP FAD CO E1)E2 NADH+H+ CH3-C-S FAD TPP E1E2 NAD+ oxidized lipoyllysine reduced FADH lipoyllysine CoA-SH TPPE1 E2 E3 E1E2Es CHa-C-SCoA TPP AD Acetyl-CoA The oxidative decarboxylation of pyruvate is catalyzed by a multienzyme complex: pyruvate dehydrogenase complex
The oxidative decarboxylation of pyruvate is catalyzed by a multiezyme complex: pyruvate dehydrogenase complex
R R C N-C—CH C N-C-CH H++b-0=C8++⊙C HO-C—C CH S-C CH. S-C R Pyruvate Carbanion of TPP Addition compound 00 C eN-C-CH, CO C-CH3 N-C--CH HO-C--C HO-C=C ←→HO-C-C s-C CH S-C CH R R R Addition compound Resonance forms of ionized hydroxyethyl- TPP With the help of TPP, pyruvate is decarboxylated identical reaction as catalyzed by pyruvate decarboxylase
With the help of TPP, pyruvate is decarboxylated: identical reaction as catalyzed by pyruvate decarboxylase
Oxidized Reduced Acetylated orm fc orm form LCH HS-CH2 CH3-C-S-CH2 CH CHe CHe 2 S CH HS-CH HS--CH Lipoic CH2 CH CH2 aci CHa CH2 Dihydrolipoyl CH2 C=0 HN CH2 The lipoyllysyl group CH 2 serves as the lectron of e. CH2 CH2 and acetyl carriers CH N Polypeptide chain of H Eo(dihydrolipoyl transacetylase)
Dihydrolipoyl The lipoyllysyl group serves as the lectron and acetyl carriers
Reactive thiol group NH H H H CH3 aDenine HS--CH2-CH2-l -CH2-CH -CH2-0-P-0-P-0-CH2 O B-Mercapto- O OHCH3 ethylamine HH Pantothenic acid Ribose-3′ phosphate O OH O=P-0 CHa-c S-CoA 3'-Phosphoadenosine diphosphate Acetyl-CoA Coenzyme A Coenzyme A(CoA-SH): discovered in 1945 by Lipmann, one of the carrier molecules deliver activated acyl groups(with 2-24 Carbons) for degradation or biosynthesis
Coenzyme A (CoA-SH): discovered in 1945 by Lipmann, one of the “carrier molecules”, deliver activated acyl groups (with 2-24 Carbons) for degradation or biosynthesis
3. The complete oxidation of pyruvate in animal tissues was proposed to undergo via a cyclic pathway O2 consumption and pyruvate oxidation in minced muscle tissues were found to be stimulated by some four-carbon dicarboxylic acids(Fumarate, succinate. malate and oxaloacetate five-carbon dicarboxylic acid(o -ketoglutarate ) or Six-carbon tricarboxylic acids (citrate, isocitrate, cis-aconitate A small amount of any of these organic acids stimulates many folds of pyruvate oxidation! Malonate inhibits pyruvate oxidation regardless of which active organic acid is added
3. The complete oxidation of pyruvate in animal tissues was proposed to undergo via a cyclic pathway • O2 consumption and pyruvate oxidation in minced muscle tissues were found to be stimulated by some four-carbon dicarboxylic acids (Fumarate, succinate, malate and oxaloacetate, five-carbon dicarboxylic acid (a-ketoglutarate ), or six-carbon tricarboxylic acids (citrate, isocitrate, cis-aconitate). • A small amount of any of these organic acids stimulates many folds of pyruvate oxidation! • Malonate inhibits pyruvate oxidation regardless of which active organic acid is added!