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Welcome to Metabolism…..
Time to put some LIFE into the subject
What is Life?
What are the properties of life?
Movement
Turnover of components
Reproduction of one’s kind
Energy Transformations
Chemical Energy is the Dominant Energy
Form in a Living System
Metabolism:
The process by which a living system
derives or uses energy through
chemical change
Energy
A
B
Anabolism: Synthesis. Putting free
energy to work
Endergonic
Catabolism: Degradation. Deriving free energy
Exergonic
ATP: Energy currency. The standard that is used
to gauge all energy compounds
The 5 Rules of Energy Metabolism
Rule: Living system are able to conserve energy
Rule: Heat is wasted energy
Heat is energy that cannot be conserved
Rule: Living systems will do their utmost to prevent
lost of free energy as heat
Rule: Exergonic biochemical transformations channel
a large part of the free energy into chemical
bonds of the product.
Rule: Catabolic reactions drive anabolic reactions
O
O
O
HO-P-O~P-O
O
O
C ~O-P-O
O
O
Phosphoanhydride
bond
+ NH2
O
Acylphosphate
bond
(mixed anhydride)
C
HO-P~ NH
O
High Energy
Compounds
N
CH2-COO-
CH3
Nitrogen-Phosphate
bond
Phosphocreatine
Enol-phosphate
bond
OOC
O
C~O-P-OH
CH2 O
O
Phosphoenol pyruvate
(PEP)
Thioester
bond
CH3-C~S-CoA
Acetyl-Coenzyme A
(Acetyl-CoA)
See Strategies
p.173-174
Careful- Phosphate Esters are Not High Energy!
-CH2O H
Alcohol
O
Water
+ HO P OH
O
Acid
Phosphate ester (low energy)
Putting High Energy Concepts to Work
O
Low energy phosphate ester
C H
+ ADP
H- C-OH O
NO REACTION
CH2O-P O
Glyceraldehyde O
3-PO4
O
High energy phosphoanhydride
O
C O-P-O
O
+ ADP
H- C-OH O
CH2O-P O
1,3-bisPO4
O
glycerate
O
C O
H- C-OH O
+ ATP
CH2O-P O
O
WHY?
Chemical reactions depend on breaking and
making bonds
Breaking a bond makes energy available to make
a bond
Breaking a phosphate ester bond (low energy) does
not release energy sufficient to make an
phosphoanhydride bond (high energy)
ERGO: You can’t use a spitball to fire a cannon
Coupled Reactions
Glucose + Pi
ATP + H2O
Glucose-6-P + H2O
Go’ = +13.8 kJ/mol
ADP + Pi
Go’ = - 30.5 kJ/mol
Coupling depends on a common intermediate
in both reactions
Glucose + Pi
Glucose-6-P + H2O
ATP + H2O
ADP + Pi
Glucose + ATP
Glucose-6-P + ADP
Go’ = - 16.7 kJ/mol
Anaerobic
Aerobic
Oxidized
cofactors
(recycle back
Reduced
cofactors
(drive Ox Phos)
The Glycolysis Pathway
•
•
•
•
•
Major anaerobic pathway in all cells
NAD+ is the major oxidant
Requires PO4
Generates 2 ATP’s per glucose oxidized
End product is lactate (mammals) or ethanol
(yeast)
• Connects with Krebs cycle via pyruvate
Glycolysis
Two Stages
a-D-Glucose
OH
1. Hexose stage
2. Triose stage
Hexose
CH2OH
O
Hexokinase
Glucose-6-Phosphate
ATP
CH2OPO3
O
OH
Phosphoglucoisomerase
Fructose-6-Phosphate
CH2OPO3
O CH2OH
OH
CH2OPO3
O CH2OH
Fructose-6-Phosphate
OH
ATP
Phosphofructokinase-I
CH2OPO3
O CH2OPO3
Fructose 1,6-Bisphosphate
OH
CHO
CH2OPO3
C=O
Aldolase
CH2OH
Dihydroxyacetone-Phosphate
H-C-OH
CH2OPO3
Glyceraldehyde-3-Phosphate
Hexose Stage Reactions
CHO
OPO3
2OH
Fructose-6-Phosphate
C-OH
=O
Glucose-6-Phosphate
HO-C
C-OH
Fructose 1,6-Bisphosphate
C-OH
CH2OH
PO3
Phosphoglucoisomerase
HEXOKINASE
Phosphofructokinase-I
o
G
Kj/mol
Goo=
-14.2kJ/mol
kJ/mol
G
== -16.7
+1.7
ATP
Preparing for the Triose Stage
ALDOLASE
Fructose 1,6bisphosphate
CH2OP
C=O
HO-C-H
..
H-C-OH
C-OH
CH23OH
PO3=
CH2OP
C=O
CH
CH23OH
DihydroxyAcetone Phosphate
CH2OP
C=O
HO-C-H
..
H
+
CHO
H-C-OH
Dihydroxy
Acetone
Phosphate
(DHAP)
C-OH
CH2OP
Glyceraldehyde-3-P
Triose Stage
Dihydroxy
acetone
phosphate
(DHAP)
CH2OPO3
CHO
Glyceraldehyde
3-phosphate
H-C-OH
C=O
CH2OH
CH2OPO3
Triose phosphate isomerase
CHO
PO4
H-C-OH
CH2OPO3 NAD+
Glyceraldehyde-3-P
Dehydrogenase
O
C ~OPO3
COO
H-C-OH
ADP
CH2OPO3
NADH
+ H+ 1,3 bisphosphoglycerate
H-C-OH
ATP CH OPO
2
3
3-phosphoPhosphoglycerate
glycerate
Kinase
COO
COO
H-C-OH
H-C-OPO3
CH2OPO3
3-PGA
-H2O
C~OPO3 PEP
CH2OH
2-PGA
Phosphoglyceromutase
COO
CH2
ADP
Enolase
Pyruvate kinase
ATP
Back to Glycolysis
COO NADH + H+ COO
C=O
HO-C-H
CH3
L-lactate
NAD+
CH3
Pyruvate
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