Acetyl-CoAandtheCitricAcidCycle

Dr.KevinAhern

Respiration

Conversionofnutrientsintousefulenergyforthecell

Carbohydrates-Sugars

Proteins-AminoAcids

Fats-FattyAcids&Glycerol

Acetyl-CoA

PyruvateDehydrogenase

MitochondrialEnzyme

VerylargemultimericcomplexThreesubunits-E1,E2,E3

E1 Subunit of Pyruvate Dehydrogenase

Pyruvate Acetaldehyde

Acetyl-CoA

CO2

NADH + CO2

NAD+

Bacteria & Yeast

AnimalsNAD+

NADH

O2

No O2

Ethanol

NADHNAD+

Acetaldehyde EthanolAlcohol

Dehydrogenase

NADH NAD+

Pyruvate

TPP-Acetaldehyde

Acetyl-Lipoamide

Acetyl-CoA

E1

E2

E3

CO2

Electron transfer to lipoamide-S-S

Pyru

vate

Deh

ydro

gena

se

FADFADH2NAD+

NADH

AcetaldehydeBacteria / Yeast

(Mostly in low O2)

Pyruvate

TPP-AcetaldehydeAcetyl-Lipoamide

Electron transfer

to lipoamide-S-S

Acetyl-CoA

E1

E2

E3

Lipoamide Oxidized/Reduced

PD = Pyruvate Dehydrogenase Phosphorylation Inactivates Dephosphorylation Activates PD Kinase Puts Phosphate on

PD Phosphatase Takes Phosphate off

These Hormones Inactivate PD (Favor Phosphorylation)

These ions Activate (Favor D

ephosphorylation)Be careful not to confuse PD with the PD Phosphatase

or the PD Kinase

Acetyl-CoA

+

+ H

Citrate Synthase

Very Negative ΔG°’

Aconitase

+ NAD+

+ NADH + CO2

Isocitrate Dehydrogenase

First oxidative decarboxylation

+ NAD+ + CoASH

+ NADH + CO2

α-ketoglutarate dehydrogenase

Second oxidative decarboxylation

+ GDP + Pi

+ GTP + CoASH

Succinyl-CoA Synthetase

Symmetrical ProductOnly Substrate Level

Phosphorylation in Cycle

Succinyl-CoA Synthetase Mechanism

+ FAD

+ FADH2

Succinate Dehydrogenase

Third Oxidation of Cycle

Succinate Dehydrogenase

Enzyme is embedded in inner mitochondrial membrane Only enzyme of Citric Acid Cycle not found in matrix

Reaction

Electron Movement

+ H2O

Fumarase

+ NAD+

+ NADH

Malate Dehydrogenase

Fourth and final oxidation of cycle

Very positive ΔG°’ Reaction pulled by

citrate synthase reaction

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

IsocitrateLyase

Isocitrate Succinate+Glyoxylate

+

MalateSynthase

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

TheAnimals’Dilemma

Nonetglucosesynthesisfromfat

KetoneBodyMetabolism