Stages of Metabolism
Pyruvate Oxidation
Conversion to acetyl–CoA
• Catalyzed by pyruvate
dehydrogenase
• Decarboxylation - gives CO2
and aldehyde (uses thiamine
pyrophosphate)
• Oxidation - gives acetyl
group (uses FAD and NAD+ ,
makes NADH)
• Transfer to CoASH (uses
lipoic acid)
pyruvate
dehydrogenase
complex
O
C
O–
C
O
CoASH
CO2
S CoA
C
CH 3
pyruvate
NAD+
NADH + H +
O
CH 3
acetyl–CoA
Citric Acid Cycle Overview
In the citric acid cycle,
• Acetyl (2C) bonds to
oxaloacetate (4C) to form
citrate (6C).
• Oxidation and
decarboxylation reactions
convert citrate to
oxaloacetate.
• Oxaloacetate bonds with
another acetyl to repeat the
cycle.
Citric Acid Cycle
The citric acid cycle (stage 3)
• Operates under aerobic conditions only.
• Oxidizes the two-carbon acetyl group in
acetyl CoA to 2CO2.
• Produces reduced coenzymes NADH
and FADH2 and one ATP directly.
Citric Acid Cycle
Entry from Acetyl–CoA
Citric Acid Cycle
Citrate to Isocitrate
Citric Acid Cycle
First Oxidation
Key point: requires NAD+
Citric Acid Cycle
Second Oxidation
Key point: requires NAD+
Citric Acid Cycle
Substrate-Level Phosphorylation
Citric Acid Cycle
Third Oxidation
Citric Acid Cycle
Hydration
Citric Acid Cycle
Fourth Oxidation
Key point: requires NAD+
An acetyl group bonds with oxaloacetate to form citrate
Two decarboxylations remove two carbons as 2CO2
Four oxidations provide hydrogen for 3NADH and one FADH2.
A direct phosphorylation forms GTP (ATP).
Overall Chemical Reaction for
the Citric Acid Cycle
acetyl-SCoA + 3NAD+ + FAD + GDP + Pi + 2H2O
2CO2 + 3NADH + 3H+ + FADH2 + HS-CoA + GTP
One turn of the citric acid cycle produces:
2 CO2
3 NADH
1 FADH2
1 GTP (1ATP)
1 HS-COA
Pyruvate
(cytoplasm)
Pyruvate
(mitoc hondria)
CoASH
Fatty
acids
NADH + H +
CO 2
O
CH3C
Choles terol
SCoA
acetyl – CoA
Energized
acetyl group
Condensation
(very favorable
reaction)
CO2
CO2
CH2
HO
C
CO2
CH2
CO2
citrate
CO 2
Glucos e
C
Amino
ac ids
Citric Acid Cycle
NAD+
H
C
OH
H
C
CO2
Conversion of 3 o alcohol
into 2 o alcohol: Now
able to be oxidized
NAD+
Oxidative
decarboxylation
CH2
NADH + H +
CO2
is ocitrate
O
CO 2
CH 2
CO2
CO 2
C
oxaloacetate
O
Amino
acids
CH2
NADH + H +
Oxidation of
2 o alcohol
Oxidation
Ins ertion of double
bond as first step
towards regeneration
of oxaloacetate
CO 2
NAD+
CO2
HO
C
CO2
H
CH
CH2
CO2
H2O
L- malate
Addition
of water to
create a 2 o
alcohol.
C
FADH 2
fumarate
FAD CO 2
GDP
+ Pi
GTP
su ccinate
Heme
Amino
ac ids
CoASH
O
CO 2
NAD+
Oxidative decarboxylation
coupled to formation
of an energized molecule
CH 2
CH 2
CO2
CO2
-ketoglutarate
SCoA
CoASH
CH 2
HC
CH2
Substrate-level
phos phorylation.
The energized succinate
is us ed to drive the
phos phorylation of GDP.
CH 2
NADH + H +
CO 2
Amino
su ccinyl – Co A ac ids
Regulation of Citric Acid Cycle
The reaction rate for
the citric acid cycle
Increases when high levels
of ADP or NAD+ activate
isocitrate dehydrogenase and
-ketoglutarate dehydrogenase
Decreases when high levels
of ATP or NADH inhibit
isocitrate dehydrogenase.
Decreases when high levels
of NADH or succinyl–CoA
inhibit -ketoglutarate dehydrogenase.
Formation of acetyl–CoA from pyruvate (catalyzed by pyruvate
dehydrogenase) also activated by ADP and inhibited by ATP and NADH.
Mitochondrial
Structure
FMN (Flavin mononucleotide)
FMN coenzyme
• Contains flavin,
ribitol,and
phosphate.
• Accepts 2H+ +
2e- to form
reduced
coenzyme
FMNH2.
Coenzyme Q (Q or CoQ)
Coenzyme Q (Q or CoQ) is
• A mobile electron carrier derived from quinone.
• Reduced when the keto groups accept 2H+ and 2e-
Cytochromes
Cytochromes (cyt) are
• Proteins containing
heme groups with
iron ions.
Fe3+ + 1eFe2+
• Abbreviated as cyt a,
cyt a3, cyt b, cyt c,
and cyt c1.
Electron Transport Chain
Cyt
c1
2 NADH + 2 H+ + O2
2 FADH2 + O2
2 NAD+ + 2 H2O
2 FAD + 2 H2O
Chemiosmotic Model of
Electron Transport
During electron flow Complexes I, III, and IV pump protons into the
intermembrane space creating a proton gradient.
Protons pass through ATP synthase to return to the matrix.
The flow of protons through ATP synthase provides the energy
for ATP synthesis (oxidative phosphorylation).
ATP Synthase
In ATP synthase
• Protons flow back to
the matrix through a
channel in the F0
complex.
• Proton flow provides
the energy that drives
ATP synthesis by the F1
complex
ATP from Electron Transport
From NADH (Complex I) provides
sufficient energy for 3ATPs
NADH + 3ADP + 3Pi
NAD+ + 3ATP
From FADH2 (Complex II) provides
sufficient energy for 2ATPs
FADH2 + 2ADP + 3Pi
FAD + 2ATP
Regulation of Electron Transport
The electron transport system is regulated by
High levels of ADP and NADH that activate
electron transport.
Low levels of ADP, Pi, oxygen, and
NADH that decrease electron transport activity.
ATP from Glycolysis
Reaction Pathway
ATP for One Glucose
ATP from Glycolysis
Activation of glucose
-2 ATP
Oxidation of 2 NADH (as FADH2)
4 ATP
Direct ADP phosphorylation (two triose)
4 ATP
6 ATP
Summary:
C6H12O6
glucose
2 pyruvate + 2H2O + 6 ATP
ATP from Two Pyruvates
Under aerobic conditions
• 2 pyruvate are oxidized to 2 acetyl CoA and 2 NADH.
• 2 NADH enter electron transport to provide 6 ATP.
Summary:
2 Pyruvate
2 Acetyl CoA + 6 ATP
ATP from Citric Acid Cycle
Reaction Pathway
ATP (One Glucose)
ATP from Citric Acid Cycle (2 acetyl-CoA)
Oxidation of 2 isocitrate (2NADH)
6 ATP
Oxidation of 2 -ketoglutarate (2NADH) 6 ATP
2 Direct substrate phosphorylations (2GTP) 2 ATP
Oxidation of 2 succinate (2FADH2)
4 ATP
Oxidation of 2 malate (2NADH)
6 ATP
24 ATP
Summary: 2Acetyl CoA + 24 ADP + 24 Pi
4CO2 + 2H2O + 24 ATP + 2 CoASH
ATP from Glucose
One glucose molecule undergoing complete oxidation
provides:
From glycolysis
6 – 8 ATP
From 2 pyruvate
6 ATP
From 2 acetyl CoA
24 ATP
36-38 ATP
Overall ATP Production for one glucose
C6H12O6 + 6O2 + (36 – 38)ADP + (36 – 38) Pi
glucose
6CO2 + 6H2O + (36 – 38) ATP
ATP Energy from Glucose
The complete
oxidation of
glucose yields
• 6 CO2
• 6 H2O
• 36-38 ATP