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Biochemistry
Lecture 13
Citric Acid Cycle
Only a Small Amount of Energy
Available in Glucose is Captured in
Glycolysis
Glycolysis
G’° = -146 kJ/mol
2
GLUCOSE
Full oxidation (+ 6 O2)
G’° = -2,840 kJ/mol
6 CO2 + 6 H2O
Cellular Respiration: the big picture
• process in which cells consume O2 and produce CO2
• provides more energy (ATP) from glucose than glycolysis
• also captures energy stored in lipids and amino acids
• evolutionary origin: developed about 2.5 billion years ago
• used by animals, plants, and many microorganisms
• occurs in three major stages:
- acetyl CoA production
- acetyl CoA oxidation
- electron transfer and oxidative phosphorylation
Stage 1. Acetyl-CoA production
Stage 2. Acetyl-CoA Oxidation
Stage 3. Electron Transfer and
oxidative Phosphorylation
Where does this all happen?
Stage 1. Acetyl-CoA production
Stage 1: Acetyl-CoA Production
pyruvate + CoA + NAD+  acetyl CoA + CO2 + NADH
+ H+
3 steps required:
What is the purpose of creating the acetyl-CoA molec
PDC
Sequence of Events
in Pyruvate Decarboxylation
•
Step 1: Decarboxylation of pyruvate to an aldehyde
• Step 2: Oxidation of aldehyde to a carboxylic acid
• Step 3: Formation of acetyl CoA
• Step 4: Reoxidation of the lipoamide cofactor
• Step 5: Regeneration of the oxidized FAD cofactor
Structure of FMN
Structure of CoA
Arsenic Poisoning
Inhibit PDC by binding dihydrolipoamide
Arsenite ion: arsenic in
the 3+ oxidation state
E2
Use sulfhydryl
reagents to
compete for
binding to the
metal ion
Stage 2. Acetyl-CoA Oxidation
TCA Cycle Sequence of Events
Step 1: C-C bond formation to make citrate
Step 2: Isomerization via dehydration/rehydration
Step 3-4: Oxidative decarboxylations to give 2
NADH
Step 5: Substrate-level phosphorylation to give GTP
Step 6: Dehydrogenation to give reduced FADH2
Step 7: Hydration
Step 8: Dehydrogenation to give NADH
Sterospecificity
Step 3
Step 5.
Carbons are scrambled at succinate
*
Succinyl-CoA
Synthetase
Succinyl-CoA
1/2 *
Succinate
dehydrogenase
Succinate
1/2*
Step 7.
Products from one turn of the cycle
Net Effect of the Citric Acid Cycle
Acetyl-CoA + 3NAD+ + FAD + GDP + Pi + 2 H2O
2CO2 +3NADH + FADH2 + GTP + CoA + 3H+
•
carbons of acetyl groups in acetyl-CoA are
oxidized to CO2
• electrons from this process reduce NAD+ and FAD
• one GTP is formed per cycle, this can be
converted to ATP
• intermediates in the cycle are not depleted
Energy Yield