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Chemistry 2100
Lecture 13
Metabolism
• digestion: hydrolysis
• degradation: nutrients acetyl CoA
• TCA Cycle: acetyl CoA CO2 + NADH / FADH2
• oxidative phosphorylation: NADH / FADH2 ATP
Stages of Catabolism
Catabolic Pathways
• Two principal types of compounds participating in the common catabolic pathway are:– AMP, ADP, and ATP: agents for the
storage and transfer of phosphate groups.
– NAD+/NADH and FAD/FADH2: agents for the transfer of electrons in biological oxidation-reduction reactions
N
N
N
N
NH2
OHOH
CH2
O OH
O
OH
O
OH
O
OHPOPOPO
Ad
Adenosine Triphosphate
H2O
7500 cal/mol
O P O P O P O
O
O
O
O
O
O
Ad
O P O
O
O
Ad O P O P O
O
O
O
O
+ +
H2O
7500 cal/mol
O P O P O P O
O
O
O
O
O
O
Ad
O P O
O
O
Ad O P O P O
O
O
O
O
+ +
H2O
7500 cal/mol
O P O P O P O
O
O
O
O
O
O
Ad
O P O
O
O
Ad O P O P O
O
O
O
O
+ +
H2O
31.4 kJ/mol
O P O P O P O
O
O
O
O
O
OAd
O P O
O
OAd O P O P O
O
O
O
O
+ +
+ + +R C
O
OH HO R' R C
O
O R'4000 cal/mol H2 O
Coupled Reactions (and why we need them)
+ + +R C
O
OH HO R' R C
O
O R'4000 cal/mol H2 O
+ + +R C
O
OH HO R' R C
O
O R'4000 cal/mol H2 O
+ + +R C
O
OH H O R' R C
O
O R'16.7 kJ/mol H2 O
R C
O
OH +2500 cal/mol O P O P O P O
O
O
O
O
O
O
Ad
R C
O
O AdO
O
OP O P O P O
O
O
O
O
+
+
R C
O
OH +2500 cal/mol O P O P O P O
O
O
O
O
O
O
Ad
R C
O
O AdO
O
OP O P O P O
O
O
O
O
+
+
R C
O
OH +2500 cal/mol O P O P O P O
O
O
O
O
O
O
Ad
R C
O
O AdO
O
OP O P O P O
O
O
O
O
+
+
R C
O
OH +10.5 kJ/mol O P O P O P O
O
O
O
O
O
OAd
R C
O
O AdO
O
OP O P O P O
O
O
O
O
+
+
R C
O
O AdO
O
OP
O AdO
O
OP+
+
+ 6000 cal/mol
HO R'
R C
O
O R'
R C
O
O AdO
O
OP
O AdO
O
OP+
+
+ 6000 cal/mol
HO R'
R C
O
O R'
R C
O
O AdO
O
OP
O AdO
O
OP+
+
+ 6000 cal/mol
HO R'
R C
O
O R'
R C
O
O AdO
O
OP
O AdO
O
OP+
+
+25.1 kJ/mol
H O R'
R C
O
O R'
R C
O
O R'
H O R'R C
O
OH + ATP
+ AMP + PP + 14.6 kJ/mol
+
NAD+/NADH– NAD+ is a two-electron oxidizing agent, and is reduced to
NADH.– NADH is a two-electron reducing agent, and is oxidized to
NAD+. The structures shown here are the nicotinamide portions of NAD+ and NADH.
– NADH is an electron and hydrogen ion transporting molecule.
NAd
CNH2
OH
H+ 2e-
NAd
CNH2
OH H
+ +
NAD+
(oxidized form)NADH
(reduced form)
:
FAD/FADH2
– FAD is a two-electron oxidizing agent, and is reduced to FADH2.
– FADH2 is a two-electron reducing agent, and is oxidized to FAD.
– Only the flavin moiety is shown in the structures below.
AdN
N
N
NHH3C
H3C O
O
+ 2H+ + 2e-H3C
H3C O
OH
HAdN
N
N
NH
FAD FADH2
Carbohydrate Catabolism • glycolysis: glucose pyruvate acetyl CoA
• TCA Cycle: acetyl CoA CO2 + NADH / FADH2
• oxidative phosphorylation: NADH / FADH2 ATP
-2-2
(enediol)
isomerase
H OH
CH O
CH2OH
H OH
CH O
PO3CH2O
H OH
H OH
HO H
H OH
H OH
HO H HO H
O
OHH
H
C
CH2O PO3
H OH
H OHMg +2
hexokinase
ATP ADP
glucose fructose-6-phosphateglucose-6-phosphate
Glycolysis
-2-2
(enediol)
isomerase
H OH
CH O
CH2OH
H OH
CH O
PO3CH2O
H OH
H OH
HO H
H OH
H OH
HO H HO H
O
OHH
H
C
CH2O PO3
H OH
H OHMg +2
hexokinase
ATP ADP
glucose fructose-6-phosphateglucose-6-phosphate
-2-2
(enediol)
isomerase
H OH
CH O
CH2OH
H OH
CH O
PO3CH2O
H OH
H OH
HO H
H OH
H OH
HO H HO H
O
OHH
H
C
CH2O PO3
H OH
H OHMg +2
hexokinase
ATP ADP
glucose fructose-6-phosphateglucose-6-phosphate
-2-2
(enediol)
isomerase
H OH
CH O
CH2OH
H OH
CH O
PO3CH2O
H OH
H OH
HO H
H OH
H OH
HO H HO H
O
OHH
H
C
CH2O PO3
H OH
H OHMg +2
hexokinase
ATP ADP
glucose fructose-6-phosphateglucose-6-phosphate
-2-2
(enediol)
isomerase
H OH
CH O
CH2OH
H OH
CH O
PO3CH2O
H OH
H OH
HO H
H OH
H OH
HO H HO H
O
OHH
H
C
CH2O PO3
H OH
H OHMg +2
hexokinase
ATP ADP
glucose fructose-6-phosphateglucose-6-phosphate
Mg +2
hexokinase
ATP ADP
-2
-2
-2
-2
HO H
O
PO3CH2O
CH2O PO3
H O H
H OH
CH2O
OHH
PO3
OH
HHO
H
CH2O
O
PO3
fructose-1,6-diphosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
aldolase(enediol)
•
•H
phosphofructokinase
Mg +2
hexokinase
ATP ADP
-2
-2
-2
-2
HO H
O
PO3CH2O
CH2O PO3
H O H
H OH
CH2O
OHH
PO3
OH
HHO
H
CH2O
O
PO3
fructose-1,6-diphosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
aldolase(enediol)
•
•H
Mg +2
hexokinase
ATP ADP
-2
-2
-2
-2
HO H
O
PO3CH2O
CH2O PO3
H O H
H OH
CH2O
OHH
PO3
OH
HHO
H
CH2O
O
PO3
fructose-1,6-diphosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
aldolase(enediol)
•
•H
Mg +2
hexokinase
ATP ADP
-2
-2
-2
-2
HO H
O
PO3CH2O
CH2O PO3
H O H
H OH
CH2O
OHH
PO3
OH
HHO
H
CH2O
O
PO3
fructose-1,6-diphosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
aldolase(enediol)
••
•
•
H
H
Mg +2
hexokinase
ATP ADP
-2
-2
-2
-2
HO H
O
PO3CH2O
CH2O PO3
H O H
H OH
CH2O
OHH
PO3
OH
HHO
H
CH2O
O
PO3
fructose-1,6-diphosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
aldolase(enediol)
••
•
•H
H
Mg +2
hexokinase
ATP ADP
-2
-2
-2
-2
HO H
O
PO3CH2O
CH2O PO3
H O H
H OH
CH2O
OHH
PO3
OH
HHO
H
CH2O
O
PO3
fructose-1,6-diphosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
aldolase(enediol)
••
•
•H
H
Mg +2
hexokinase
ATP ADP
-2
-2
-2
-2
HO H
O
PO3CH2O
CH2O PO3
H O H
H OH
CH2O
OHH
PO3
OH
HHO
H
CH2O
O
PO3
fructose-1,6-diphosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
aldolase(enediol)
••
•
•H
H
Mg +2
hexokinase
ATP ADP
-2
-2
-2
-2
HO H
O
PO3CH2O
CH2O PO3
H O H
H OH
CH2O
OHH
PO3
OH
HHO
H
CH2O
O
PO3
fructose-1,6-diphosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
aldolase(enediol)
••
•
•H
H
••
N
H
C
O
NH2
AD
dehydrogenase
1,3-bisphospho glycerate NADH
NAD +
glyceraldehyde 3-phosphate
+
HPO4-2
+
C
CH2O
OHH
O
PO3
PO3O
N
C
O
NH2
HH
AD
C
CH2O
OHH
H
PO3
O
-2
-2
-2
CH2O PO3
mutase
glyceric acid 2-phosphate
OH PO3
O OHC
HCH2O
glyceric acid 3-phosphate
OHH
HO OC
glyceric acid1,3-diphosphate
OHH
PO3O OC
PO3CH2O
kinaseMg +2
ATPADP
-2
-2 -2
-2
1,3 bisphospho
glycerate
CH2O PO3
mutase
glyceric acid 2-phosphate
OH PO3
O OHC
HCH2O
glyceric acid 3-phosphate
OHH
HO OC
glyceric acid1,3-diphosphate
OHH
PO3O OC
PO3CH2O
kinaseMg +2
ATPADP
-2
-2 -2
-2
1,3 bisphospho
glycerate
CH2O PO3
mutase
glyceric acid 2-phosphate
OH PO3
O OHC
HCH2O
glyceric acid 3-phosphate
OHH
HO OC
glyceric acid1,3-diphosphate
OHH
PO3O OC
PO3CH2O
kinaseMg +2
ATPADP
-2
-2 -2
-2
1,3 bisphospho
glycerate
3-phospho
glycerate
CH2O PO3
mutase
glyceric acid 2-phosphate
OH PO3
O OHC
HCH2O
glyceric acid 3-phosphate
OHH
HO OC
glyceric acid1,3-diphosphate
OHH
PO3O OC
PO3CH2O
kinaseMg +2
ATPADP
-2
-2 -2
-2
1,3 bisphospho
glycerate
3-phospho
glycerate
2-phospho
glycerate
CH2O PO3
mutase
glyceric acid 2-phosphate
OH PO3
O OHC
HCH2O
glyceric acid 3-phosphate
OHH
HO OC
glyceric acid1,3-diphosphate
OHH
PO3O OC
PO3CH2O
kinaseMg +2
ATPADP
-2
-2 -2
-2
H
O2-phospho
glycerate
CH2O PO3
mutase
glyceric acid 2-phosphate
OH PO3
O OHC
HCH2O
glyceric acid 3-phosphate
OHH
HO OC
glyceric acid1,3-diphosphate
OHH
PO3O OC
PO3CH2O
kinaseMg +2
ATPADP
-2
-2 -2
-2
H
O
(-H2O)
-2
COHO
O
CH2
PO3enolase
COHO
O
CH2
Hkinase
Mg +2
ATPADP
2-phospho
glycerate
(-H2O)
-2
COHO
O
CH2
PO3enolase
COHO
O
CH2
Hkinase
Mg +2
ATPADP
(-H2O)
-2
COHO
O
CH2
PO3enolase
COHO
O
CH2
Hkinase
Mg +2
ATPADP
(-H2O)
-2
COHO
O
CH2
PO3enolase
COHO
O
CH2
Hkinase
Mg +2
ATPADP
(-H2O)
-2
COHO
O
CH2
PO3enolase
COHO
O
CH2
Hkinase
Mg +2
ATPADP
pyruvic acid
COHO
O
CH2 H
pyruvate
H+
NAD HCOHO
O
CH3 CH3
HHO
O OHCNAD +
pyruvic acid (–)-lactic acid
H OH
Anaerobic Glycolysis
pyruvate lactic acid
H+
NAD H NAD +
decarboxylase
CO 2 H
CH3
O
H
CH3
OHH
COHO
O
CH3
pyruvic acid acetaldehyde ethanol
Fermentation
pyruvate acetaldehyde
ethanol
(-H+)
NAD HNAD +COHO
O
CH3
++ H S CoA CO2
SCoA
CH3
O
acetyl CoApyruvic acid
TriCarboxylic Acid Cycle Prep
pyruvate
Acetyl-CoA production
Acetyl-CoA Oxidation
Electron Transfer and Oxidative Phosphorylation
Where does this all happen?
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
Oxidative Phosphorylation
