oregonstate.edu

Acetyl-CoA and the Citric Acid Cycle Dr. Kevin Ahern Respiration Conversion of nutrients into useful energy for the cell Carbohydrates - Sugars Proteins - Amino Acids

Fats - Fatty Acids & Glycerol Acetyl-CoA Pyruvate Dehydrogenase Ethanol Mitochondrial Enzyme

Very large multimeric complex Three subunits - E1, E2, E3 CO2 No O2 NAD+

NADH Pyruvate NAD+ Ba Acetaldehyde ct An

+ er NAD ia im O2 & al

s Ye as NADH t NADH + CO2

E1 Subunit of Pyruvate Dehydrogenase Acetyl-CoA NAD+ Acetaldehyde

NADH Ethanol Alcohol Dehydrogenase Pyruvate Dehydrogenase

Pyruvate E1 CO2 Bacteria / Yeast TPP-Acetaldehyde(Mostly in low O ) Acetaldehyde

2 E2 Electron transfer to lipoamide-S-S Acetyl-Lipoamide

FAD E3 FADH2 NAD+ NADH

Acetyl-CoA TPP-Acetaldehyde Acetyl-Lipoamide E2

E1 Pyruvate r e f s S n

r a - St n id e o r t am c e El lipo

to E3 Acetyl-CoA Lipoamide Oxidized/Reduced

Be careful not to confuse PD with the PD Phosphatase or the PD Kinase These Hormones Inactivate PD (Favor Phosphorylation) These ions Activate

(Favor Dephosphorylation) PD = Pyruvate Dehydrogenase Phosphorylation Inactivates Dephosphorylation Activates PD Kinase Puts Phosphate on PD Phosphatase Takes Phosphate off

Acetyl-CoA + Very Negative GG Citrate Synthase

+ H Aconitase +

NAD+ Isocitrate Dehydrogenase +

NADH + CO2 First oxidative decarboxylation + NAD+

+ CoASH -ketoglutarate dehydrogenase + NADH + CO2

Second oxidative decarboxylation + GDP + Pi Succinyl-CoA Synthetase

+ GTP + CoASH Symmetrical Product Only Substrate Level Phosphorylation in Cycle Succinyl-CoA Synthetase Mechanism + FAD

Succinate Dehydrogenase Third Oxidation of Cycle + FADH2 Succinate Dehydrogenase

nzyme is embedded in inner mitochondrial membrane Only enzyme of Citric Acid Cycle not found in matrix Electron Movement Reaction

+ H2O Fumarase + NAD+ Malate Dehydrogenase

Very positive GG Reaction pulled by citrate synthase reaction Fourth and final oxidation of cycle

+ NADH Citric Acid Cycle Summary Input 2 Carbons (1 Acetyl CoA) Release 2 CO2 Molecules Four Oxidations 3 NADH, 1 FADH2, 1 GTP Per Turn of Cycle

Each Citric Acid Cycle Intermediate Functions in Other Pathways Citrate - Glyoxylate Cycle, Allosteric Effector, Shuttle System Isocitrate - Glyoxylate Cycle a-Ketoglutarate - Amino Acid/Nitrogen Metabolism Succinyl-CoA - Heme Synthesis, Amino Acid Metabolism Succinate - Glyoxylate Metabolism, Odd Chain Fatty Acid Metabolism

Fumarate - Nucleotide Metabolism Malate - Shuttle System Oxaloacetate - Gluconeogenesis, Amino Acid Metabolism Anaplerotic / Cataplerotic Arnon-Buchanan Cycle

Two per turn of cycle Isocitrate Lyase Isocitrate Succinate + Glyoxylate

+ Malate Synthase Acetyl-CoA + Glyoxylate +

L-Malate Glyoxylate Cycle Summary Input 4 Carbons (2-Acetyl CoA) Releases 0 CO2 Molecules Produces One Extra Oxaloacetate Two Oxidations

1 NADH, 1 FADH2 1(extra ) Oxaloacetate Per Turn of Cycle Net Synthesis of Glucose from Acetyl-CoA Citric Acid Cycle Summary Input 2 Carbons (1 Acetyl CoA) Releases 2 CO2 Molecules Four Oxidations 3 NADH, 1 FADH2, 1 GTP Per Turn of Cycle No Net Synthesis of Glucose from Acetyl-CoA

The Animals Dilemma No net glucose synthesis from fat Ketone Body Metabolism

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