3. The complex of physical and chemical
processes occurring within a living cell or
organism that are necessary for the
maintenance of life.
In metabolism some substances are broken
down to yield energy for vital processes while
other substances, necessary for life, are
synthesized.
4.
5.
6. 1. Occurs in the cytosol outside the
mitochondria.
2. The breakdown of glucose to 2 pyruvate
molecules.
7. 1. Glycolysis begins with addition of 2
phosphate groups, activating glucose to react.
2. Two separate reactions use 2 ATP.
3. Glucose, a C6 molecule, splits into two C3
molecules, each with a phosphate group.
11. 2. Phosphoglucose Isomerase catalyzes:
glucose-6-P (aldose) fructose-6-P (ketose)
H O
O H
H
O HH
O H
CH 2O PO 3
2
H
O H
H
1
6
5
4
3 2
CH 2O PO 3
2
O H
CH 2O H
H
O H H
H HO
O
6
5
4 3
2
1
glucose-6-phosphate fructose-6-phosphate
Phosphoglucose Isom erase
12. 3. Phosphofructokinase catalyzes:
Fructose-6-P + ATP fructose-1,6-bisP + ADP
CH 2O PO 3
2
O H
CH 2O H
H
O H H
H HO
O
6
5
4 3
2
1 CH 2O PO 3
2
O H
CH 2O PO 3
2
H
O H H
H HO
O
6
5
4 3
2
1
ATP ADP
Mg
2+
fructose-6-phosphate fructose-1,6-bisphosphate
Phosphofructokinase
13. 4. Aldolase catalyzes:
fructose-1,6-bisphosphate
dihydroxyacetone-P + glyceraldehyde-3-P
.
6
5
4
3
2
1CH 2O PO 3
2
C
C
C
C
CH 2O PO 3
2
O
HO H
H O H
H O H
3
2
1
CH 2O PO 3
2
C
CH 2O H
O
C
C
CH 2O PO 3
2
H O
H O H+
1
2
3
fructose-1,6-
bisphosphate
Aldolase
dihydroxyacetone glyceraldehyde-3-
phosphate phosphate
Triosephosphate Isom erase
14. 5. Triose Phosphate Isomerase (TIM) catalyzes:
dihydroxyacetone-P glyceraldehyde-3-P
6
5
4
3
2
1CH 2O PO 3
2
C
C
C
C
CH 2O PO 3
2
O
HO H
H O H
H O H
3
2
1
CH 2O PO 3
2
C
CH 2O H
O
C
C
CH 2O PO 3
2
H O
H O H+
1
2
3
fructose-1,6-
bisphosphate
Aldolase
dihydroxyacetone glyceraldehyde -3-
phosphate phosphate
Triosephosphate Isom erase
15. C
C
CH 2O H
O O
H O PO 3
2
2
3
1
C
C
CH 2O PO 3
2
O O
H O H
2
3
1
3-phosphoglycerate 2-phosphoglycerate
Phosphoglycerate M utase
C
C
CH2OPO3
2
O O
H OPO3
2
2
3
1
2,3-bisphosphoglycerate
An active site histidine side-chain
participates in Pi transfer, by
donating & accepting phosphate.
The process involves a
2,3-bisphosphate intermediate.
16. 9. Enolase catalyzes:
2-phosphoglycerate phosphoenolpyruvate + H2O
C
C
C H 2O H
O O
H O PO 3
2
C
C
C H 2O H
O O
O PO 3
2
C
C
C H 2
O O
O PO 3
2
O H
2
3
1
2
3
1
H
2-phosphoglycerate enolate intermediate phosphoenolpyruvate
Enolase
17. 10. Pyruvate Kinase catalyzes:
phosphoenolpyruvate + ADP pyruvate +
ATP
C
C
CH 3
O O
O
2
3
1
A D P A T P
C
C
CH 2
O O
O PO 3
2
2
3
1
p h o sp h o en o lp yru vate p yru vate
P yru v ate K in ase
18. C
C
CH 3
O O
O
2
3
1
A D P A T PC
C
CH 2
O O
O PO 3
2
2
3
1
C
C
CH 2
O O
O H
2
3
1
phosphoenolpyruvate enolpyruvate pyruvate
Pyruvate K inase
26. Glucose + 2 ADP + 2 NAD+ + 2 Pi ---
--
> 2 Pyruvate + 2 ATP + 2 NADH + 2
H+
ATP utilized: 2
ATP produced: 4
NADH produced:2X3= 6
Total : 10- 2 = 8
Energy (Aerobic)
27. Glucose
2 Pyruvate
2 Ethanol 2 Acetyl-CoA 2 Lactate
4 CO 2 + 4 H 2O
Glycolysis
2 CO 2 –O 2 –O 2
+O 2
+O 2
CO 2
(yeast) (muscle)
28. What are the possible fates of pyruvate?
•Ethanol (fermentation)
•Acetyl coA (mammals and others)
•TCA/Krebs cycle
•Lactate (mammals and others)
•End product of anaerobic glycolysis
•Gluconeogenesis in liver via the Cori cycle
29. In the presence of oxygen pyruvate is transported
into the mitochondria where it enters the next
major metabolic pathway for the production of
ATP energy.
If there is no oxygen present then the pyruvate is
converted to a substance called lactate
The reaction involves nucleophilic attack of the C6 hydroxyl O of glucose on P of the terminal phosphate of ATP. ATP binds to the enzyme as a complex with Mg++.
The mechanism involves acid/base catalysis, with ring opening, isomerization via an enediolate intermediate, and then ring closure. A similar reaction catalyzed by TriosephosphateIsomerase will be presented in detail.
This highly spontaneous reaction has a mechanism similar to that of Hexokinase. The Phosphofructokinase reaction is the rate-limiting step of Glycolysis.
The reaction is an aldol cleavage, the reverse of an aldol condensation.
Glycolysis continues from glyceraldehyde-3-P. TIM's Keq favors dihydroxyacetone-P. Removal of glyceraldehyde-3-P by a subsequent spontaneous reaction allows throughput
This dehydration reaction is Mg++-dependent. 2 Mg++ ions interact with oxygen atoms of the substrate carboxyl group at the active site.The Mg++ ions help to stabilize the enolate anion intermediate that forms when a Lys extracts H+ from C #2.
This phosphate transfer from PEP to ADP is spontaneous. PEP has a larger DG of phosphate hydrolysis than ATP.Removal of Pi from PEP yields an unstable enol, which spontaneously converts to the keto form of pyruvate. Required inorganic cations K+ and Mg++ bind to anionic residues at the active site of PyruvateKinase.