TCA - Cellular Respiration: three stages Stage 1 . Acetyl...

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Unformatted text preview: Cellular Respiration: three stages Stage 1 . Acetyl CoA production from glucose, lipids and amino acids Stage 2 . Acetyl CoA oxidation via TCA Cycle = yielding reduced electron carriers & CO 2 Stage 3 . Electron transport and oxidative phosphorylation oxidation of these carriers and oxidative phosphorylation to make ATP *************************************************** Acetyl CoA HS-CoA Space filled Acetyl A high energy bond 0- Conversion of pyruvate to acetyl-CoA -- A major Stage 1 setup Enzyme = pyruvate dehydrogenase complex Location = mitochondrial matrix CH 3 CH 3 C=O + NAD + + HS-CoA C=O +NADH+CO 2 COO- S-CoA Pyruvate Acetyl-CoA (A high energy compound) Irreversible-- irreversible means acetyl-CoA cannot be converted backward to pyruvate; hence fat cannot be converted to carbohydrate Complex of 2.5 x 10 6 Da, including multiple copies of three enzymes pyruvate dehydrogenase (=E 1 ) has coenzyme = thiamine pyrophosphate (TPP) dihydrolipoyl transacetylase (=E 2 ) has coenzymes lipoate and CoA dihydrolipoyl dehydrogenase (= E 3 ) has coenzymes FAD and NAD + S-- S-- TPP FAD E 1 E 2 E 3 N A D + Also contains regulatory kinase & phosphatase thiamine pyrophosphate (TPP) lipoic acid aka lipoamide Flavin mononucleotide = FMN Flavin adenine dinucleotide = FAD Riboflavin = ring + ribitol i soalloxazine ring ribitol Reduced form = FADH 2 Transfer 2 H atoms with 2e- or 2H Reaction AH 2 + E-FMN = A +E-FMNH 2 Partial reactions of PDH : introduction of pyruvate onto TPP in E 1 hydroxyethyl-TPP H H O O CO 2 O- O-C-C-CH 3 H-CCH 3 TPP E 1 E 1 Transfer to lipoamide of E 2 hydroxyethyl-TPP + O CH 3 + TPP S C S S HS E 2 E 2 lipoamide-E 2 acetyl-lipoamide-E 2 (disulfide,oxidized) (reduced) Note concurrent oxidation to acetyl and reduction of S E 2 then transfers acetyl to CoA; acetyl-CoA leaves . E 3 uses its bound coenzyme FAD to oxidize lipoamide back to disulfide thereby generating FADH 2 . FAD is recovered from FADH 2 via reducing NAD to NADH. An NADH is generated. Regulation of Pyruvate Dehydrogenase Irreversible reaction must be tightly controlled-- three ways 1. Allosteric Inhibition-- inhibited by products: acetyl-CoA and NADH -- inhibited by high ATP 2. Allosteric activation by AMP Ratio ATP/AMP important 3. Phosphorylation/dephosphorylation of E 1 subunit P i E 1-OH ATP (active) phosphatase kinase activator = activator = insulin acetyl-CoA indirectly NADH, not cAMP H 2 O E 1-OP ADP (inactive) kinase inhibitors = pyruvate, ADP CITRIC ACID CYCLE = TCA CYCLE = KREBS CYCLE TCA = tricarboxylic acid cycle Definition:...
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TCA - Cellular Respiration: three stages Stage 1 . Acetyl...

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