Post on 27-Aug-2019
Glycolysis and Fermentation
O OH
HH
OH
OH
H
H
OH
CH2
H
HO
Glucose
H
C
C
CH3
O
O
HO
L-Lactate
2 ATP + 2 H2O2 ADP + 2 inorganic phosphate + + 2
O OH
HH
OH
OH
H
H
OH
CH2
H
HO
Glucose
2 ATP + 2 H2O2 ADP + 2 inorganic phosphate + + 2 CH2CH3
HO
Ethanol
+ 2 CO2
!G´° = +61.0 kJ/mol2 ADP + 2 inorganic phosphate 2 ATP + 2 H2O
Glucose 2 L-Lactic acid
Glucose + 2 ADP + 2 inorganic phosphate 2 ATP + 2 H2O
2 L-Lactic acid+
!G´° = –183.6 kJ/mol
!G´° = –122.6 kJ/mol
Overall Process
O OH
HH
OH
OH
H
H
OH
CH2
H
HO
Glucose
6 CO2 + 6 H2O6 O2 +!G´° = –2870 kJ/mol
Pyruvate and Lactate Glucose + 2 ADP + 2 phosphate → 2 Pyruvate + 2 ATP + 2 H2O
+ 2 NAD + 2 NADH
Glucose + 2 ADP + 2 phosphate → 2 L-Lactic acid + 2 ATP + 2 H2O
Glucose Transport
Most cells: Skeletal Muscle & Adipose Tissue: Liver:
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O OH
HH
OH
OH
H
H
OH
CH2
H
HO
Glucose
Outside
Inside
O OH
HH
OH
OH
H
H
OH
CH2
H
HO
Glucose
Glucose Phosphorylation
Saccharomyces cerevisiae hexokinase structures from pdb ID 2YHX (left) and 2YHX superimposed on 1HKG (right)
O OH
HH
OH
OH
H
H
OH
CH2
H
HO
Glucose Glucose-6-phosphate
ATP ADP
HexokinaseGlucokinase
O
PO O
O
O OH
HH
OH
OH
H
H
OH
CH2
H
!G´° = –16.6 kJ/mol
P
O
O
O O P
O
O
O
HH
OHOHH
CH2
H
O
N
N N
N
NH2
P
O
O
O
Adenosine Triphosphate(ATP)
!G´° = –30.5 kJ/mol
H2O+
O P
O
O
O
HH
OHOHH
CH2
H
O
N
N N
N
NH2
P
O
O
O
Adenosine Diphosphate(ADP)
+ P
O
O
O OH
Inorganicphosphate
0
0.2
0.4
0.6
0.8
1
0 2 4 6 8 10 12
v/Vmax
[Glucose] (mM)
Hexokinase (Km
= ~0.1 mM)
Glucokinase (K0.5
= ~ 10 mM)
Glycolysis
Fructose-6-phosphate
P
O
O
O O O
O
OH
CH2
OH
CH2 OHP
O
O
O OO OH
OH
OH
OH
CH2
Glucose-6-phosphate
Phosphoglucoisomerase
Fructose-1,6-bisphosphate
P
O
O
O OP
O
O
O O O
O
OH
CH2
OH
CH2
Phosphofructokinase
ATP
ADP
C
C
CH2 O
OH
OHH
PO O
O
CH2
C
C
O
O
HO H
PO O
O
H Dihydroxy-acetonephosphate
Glyceraldehyde3-phosphate
Triosephosphateisomerase
Aldolase
O
PO O
O
C
C
CH2 O
O
OHH
PO O
O1,3-bisphospho-glycerate
Glyceraldehyde-3-phosphatedehydrogenase
NAD+Pi
ATP ADP
O
C
C
CH2 O
O
OHH
PO O
O
3-phospho-glycerate
O
PO O
O
O
C
C
CH2OH
O
H
O
PO O
O
O
C
C
CH2
O
Enolase
H2O
2-phospho-glycerate
Phosphoenolpyruvate
Phosphoglyceratekinase
Phosphoglyceratemutase
O
C
C
CH3
O
OH
Pyruvate
ATPADP
Pyruvatekinase
H
C
C
CH3
O
OH
HO
L-Lactate
Lactatedehydrogenase
NAD
NADH
NADH
H
H
P
O
O
O
O
O
O
H
H
H
O
H
H
C
H
2
O
H
C
H
2
O
H
P
O
O
O
O
O
O
H
H
H
O
H
O
H
H
H
O
H
C
H
2
H
Fructose-6-phosphateGlucose-6-phosphate
Phosphoglucoisomerase
P
O
O
O
O
O
O
H
H
H
O
H
O
H
H
H
O
H
C
H
2
H
P
O
O
O
O
H
H
O
H
O
H
H
H
O
H
C
H
2
H
O
O
H
Lys
N
H
2
+
H
Lys
N
H
2
P
O
O
O
O
H
O
O
H
H
H
O
H
C
H
2
H
O
O
H
H
H
O
H
H
P
O
O
O
O
H
O
O
H
H
H
O
H
C
H
2
H
O
O
H
H
H
N
H
N
N
H
N
N
H
N
N
H
N
+
H
Lys
N
H
2
+
H
Lys
N
H
2
Glu Glu
Glu Glu
Substrates: ATP, Fructose-6-phosphate Inhibitors: ATP, citrate, phosphoenolpyruvate Activators: AMP, ADP, Fructose-1,6-bisphosphate, Fructose-2,6-bisphosphate,
NH4+
Fructose-6-phosphate
P
O
O
O O O
OH
HOHH
CH2
OH
CH2 OH
Fructose-1,6-bisphosphate
P
O
O
O OP
O
O
O O O
OH
HOHH
CH2
OH
CH2
Phosphofructokinase
ATP ADP
H H
0
0.2
0.4
0.6
0.8
1
1.2
0 0.5 1 1.5 2 2.5 3
v/Vmax
[Fructose-6-phosphate] (mM)
Low ATP
1 mM ATP+ 0.1 mM AMP
1 mM ATP
T state Bacillus stearothermophilus phosphofructokinase pdb ID 6PFK R state Bacillus stearothermophilus phosphofructokinase pdb ID 4PFK
Aldolase
Homo sapiens aldolase bound to fructose-1,6-bisphosphate (pdb ID 4ALD)
C
H
2
1
C
2
C
3
C
4
C
5
C
H
2
6
O
O
O
O
H
H
O
H
H
O
H
H
P
P
O
O
O
O
O
O
C
H
2
1
C
2
C
3
C
4
C
5
C
H
2
6
O
O
N
+
O
H
H
O
H
O
H
H
P
P
O
O
O
O
O
O
Lys
E
n
z
H
H
N
H
2
Lys
E
n
z
O
C
O
Asp
E
n
z
C
H
2
1
C
2
C
3
O
N
O
H
H
P
O
O
O
Lys
E
n
z
H
O
C
O
H
Asp
E
n
z
C
4
C
5
C
H
2
6
O
O
H
O
H
H
P
O
O
O
C
H
2
1
C
2
C
3
O
N
O
H
H
P
O
O
O
Lys
E
n
z
H
O
C
O
Asp
E
n
z
H
C
H
2
1
C
2
C
3
O
N
+
O
H
H
P
O
O
O
Lys
E
n
z
H
H
O
C
O
Asp
E
n
z
C
H
2
1
C
2
C
3
O
O
H
H
P
O
O
O
H
O
N
H
2
Lys
E
n
z
–H2O
+H2O
Cleavage occursbetween C3 and C4(! to the carbonyl)
Glyceraldehyde3-phosphate
Fructose1,6-bisphosphate
Dihydroxyacetonephosphate
..
..
Triose Phosphate Isomerase
Saccharomyces cerevisiae triose phosphate isomerase bound to 2-phosphoglycolate (pdb ID 2YPI)
C
C
CH2 O
OH
OHH
PO O
O
CH2
C
C
O
O
HO H
PO O
O
H
Dihydroxyacetonephosphate
Glyceraldehyde3-phosphate
C
C
CH2 O
OHH
OH
PO O
O
Enediolintermediate
C
C
CH3
OH
OMethyl glyoxal
Mid-point of Glycolysis
Glyceraldehyde-3-phosphate dehydrogenase
O OH
HH
OH
OH
H
H
OH
CH2
H
HO
Glucose
+ 2 ATP
C
C
CH2 O
OH
OHH
PO O
O
Glyceraldehyde-3-phosphate
+ 2 ADP2
1. Hexokinase2. Phosphoglucoisomerase3. Phosphofructokinase4. Aldolase5. Triose phosphate isomerase
C
C
C
H
2
O
O
H
O
H
H
P
O
O
O
O
P
O
O
O
C
C
C
H
2
O
O
O
H
H
P
O
O
O
Glyceraldehyde3-phosphate
1,3-bisphosphoglycerate
Glyceraldehyde-3-phosphatedehydrogenase
NAD+Pi NADH
C
C
C
H
2
O
O
H
O
H
H
P
O
O
O
O
P
O
O
H
O
N
N
H
2
O
N
A
D
H
S
H
His
N
N
H
2
O
N
A
D
H
S
C
C
C
H
2
O
O
H
O
H
H
P
O
O
O
His
H
N
N
H
2
O
N
A
D
H
H
H
S
C
C
C
H
2
O
O
O
H
H
P
O
O
O
His
H
S
C
C
C
H
2
O
O
O
H
H
P
O
O
O
His
H
O
P
O
O
O
C
C
C
H
2
O
O
O
H
H
P
O
O
O
S
H
His
Glyceraldehyde3-phosphate
+ +
1,3-bisphosphoglycerate
Phosphoglycerate kinase
Thermotoga maritima phosphoglycerate kinase (pdb ID 1VPE)
O
P
O
O
O
C
C
C
H
2
O
O
O
H
H
P
O
O
O
O
C
C
C
H
2
O
O
O
H
H
P
O
O
O
1,3-bisphosphoglycerate
Phosphoglycerate kinase
ADP ATP
3-phosphoglycerate
Phosphoglycerate mutase
O
C
C
C
H
2
O
O
O
H
H
P
O
O
O
O
P
O
O
O
O
C
C
C
H
2
O
H
O
H
3-phosphoglycerate 2-phosphoglycerate
Phosphoglyceratemutase
O
C
C
C
H
2
O
O
O
H
H
P
O
O
O
O
P
O
O
O
O
C
C
C
H
2
O
O
H
P
O
O
O
N
N
O
P
O
O
N
N
N
N
O
P
O
O
N
N
O
P
O
O
O
O
C
C
C
H
2
O
H
O
H
3-phosphoglycerate
2,3-bisphosphoglycerate
2-phosphoglycerate
Enolase
O
CO
CH O P
O
O
OCH2
OH
2-phosphoglyceratePhosphoenol pyruvate
O
CO
C O P
O
O
OCH2Enolase
H2O
O
CO
CH O P
O
O
OCH2
OH
NN
His
H
O O
Glu
OHH
H
O O
Glu
Mg2+
O
CO
C O P
O
O
OCH2
OH
NNH
His
H
O O
Glu
H
O O
Glu
Mg2+
OHH
O
CO
C O P
O
O
OCH2
OH
NNH
His
H
O O
Glu
H
O O
Glu
Mg2+
OHH
Homarus gammarus (lobster) enolase bound to 2-phosphoglycolate and manganese (pdb ID 1PDZ)
Pyruvate kinase
Reaction ∆G´° (kJ/mol) Approximate ∆G under
erythrocyte cellular conditions (kJ/mol)
Hexokinase -16.7 -33.9
Phosphoglucoisomerase +1.67 -2.92
Phosphofructokinase -14.2 -18.8
Aldolase +23.9 -0.23
Triose phosphate isomerase +7.56 +2.41
GAP dehydrogenase +6.30 -1.29
Phosphoglycerate kinase -18.9 +0.1
Phosphoglycerate mutase +4.4 +0.83
Enolase +1.8 +1.1
Pyruvate kinase -31.7 -23.0
Lactate dehydrogenase -25.2 -14.8
CH3C
O
C
O
O
Pyruvate
+ ATPCH2C
O
C
O
O
Phosphoenolpyruvate
P
O
O OO P
O
O
O
HH
OHOHH
CH2
H
O
N
N N
N
NH2
P
O
O
O
Adenosine Diphosphate(ADP)
!G´° = +14.4 kJ/mol CH2C
O
C
O
O
Enolpyruvate
!G´° = –46 kJ/molCH2C
O
C
O
O
Enolpyruvate
Pyruvate Reduction
Fructose Metabolism
O
C
C
CH3
O
O
Pyruvate
H
C
C
CH3
O
O
HO
L-Lactate
Lactatedehydrogenase
NADNADH
O
C
C
CH3
O
OH
Pyruvate
Pyruvatedecarboxylase
OC
CH3
H
Acetaldehyde
CH2CH3
HO
Ethanol
Alcoholdehydrogenase
NADNADHCO2
Fructose Fructose-6-phosphateHexokinase
ATP ADP
Fructokinase
Dihydroxyacetone phosphate+
GlyceraldehydeFructose-1-phosphate
Fructose-1-phosphatealdolase
ATP ADP
Fructose