Biochemistry I, Spring Term
Lecture 27
March 29, 2013
Introduction to Metabolism
Required reading in Horton: 10.1-10.5. Nelson: 13.1 Bioenergetics and Thermodynamics.
Key Points




Catabolism
Anabolism
Glycolysis
Fatty acid metabolism
Metabolic pathways are:
1. Conserved in different organisms.
2. Overall irreversible (but most of the
individual steps are not)
3. Consist of a number of small changes.
4. Usually committed after the initial steps
5. Regulated (usually at initial step(s))
6. Compartmentalized in eukaryotes



Citric acid (TCA, Krebs) cycle
Electron transport
Oxidative phosphorylation (ATP
synthesis)
What you need to know:
1. Input and output metabolites
2. Steps that control flux
3. How flux is controlled
4. Cellular location of metabolic Steps
5. Selected enzyme mechanisms
6. Selected substrates/products
What you should not do: Memorize pathways.
Catabolism [degradative] – conversion of a diverse set
CH OH
Glucose
O
of compounds to a small number of simple
OH
ATP
[hexokinase]
OH OHOH
compounds for energy production.
ADP
Glucose-6-P
[isomerase]
Anabolism [synthetic] – conversion of a small number of
Fructose-6-P
ATP
[phosphofructokinase]
simple compounds to complex organic molecules.
2
Central Pathways of Energy Production:
Intracellular locations:




Glycolysis - cytosol
Fatty Acid Oxidation: Inner matrix of mitochondria
Citric Acid Cycle: Inner matrix of mitochondria
Oxidative Phosphorylation: Inner membrane of
mitochondria
Energy Currency:
Stored in the following
ways:
 "High energy" chemical
species (i.e.
phosphoanhydride
bonds in ATP):
 Redox compounds
 Membrane potentials
(concentration gradient
and voltage difference)
ADP
Fructose-1-6-P
[aldolase]
glyceraldehyde-3-P [triose phos. isomerase] dihydroxyacetone
phosphate
[glyceraldehyde-3-P
+ Pi NAD+
dehydrogenase]
NADH 1,3 bisphosphoglycerate
ADP
[phosphoglycerate kinase]
ATP
3-phosphoglycerate
[phosphoglycerate mutase]
2-phosphoglycerate
H2O
[enolase]
phosphoenol pyruvate
ADP
[pyruvate kinase]
ATP
Pyruvate CH3
O
O
O
Energy Utilization:



Chemical synthesis
reactions (e.g. protein
synthesis, DNA
synthesis
Mechanical work (e.g.
transport, muscle
function)
Electrical work (e.g.
nerve conduction)
1
Biochemistry I, Spring Term
Lecture 27
March 29, 2013
Glucose
Overall Energy Interconversion During Oxidation
of Glucose:
Overall Reaction: C6H12O6 + 6 O2 → 6CO2+6 H2O +
Energy (ATP) Go = -2823 kJ/mol
Glycolysis
Glycolysis + Citric Acid Cycle: C6H12O6 + 6H2O →
6CO2 + 24H+ + 24 e- + 4ATP
Electron Transport (oxidative phosphorylation): 24 e- +
6O2 +24 H+ →12 H2O + proton gradient across
membrane.
O
O
O
N
N
N
ATP
Synthase
ADP + P
ATP
TCA
NH2
NH2
O P O P O P O
O
O
O
Mitochondrial
Membrane
(inner)
Elec
Trans
ATP synthesis: Proton gradient + ADP & Pi → ATP
(Enzyme is also called ATPase, reverse reaction was 1st
studied.)
N
cytosol
O
ATP
OH OH
(adenosine triphospate)
N
N
O
O
O P O P O
O
O
ADP
O
N
N
O
OH OH
+
O P O
O
Pi
General Enzyme Nomenclature:
Name - usually consists of three parts:
i) the substrate is used to name the enzyme,
Keep in mind that many enzymatic reactions
run in both directions in metabolism,
consequently the “product” may be used to
name the enzyme.
ii) the nature of the chemical reaction.
iii) most names end in “-ase”
Enzymes Involved in Group Transfer Reactions:
A. Phosphatase: Removes a phosphate group from
a substrate, no ATP/ADP required. A phosphatase
is distinct from an ATPase.
B. Kinase: transfers a phosphate group from ATP to
another compound (i.e. hexokinase, galactose
kinase, pyruvate kinase). A kinase is distinct from
an ATPase
C. Mutase: Common use is to move phosphates to
different positions on sugars (i.e. phosphoglycerate
mutase).
D. Dehydrogenase: Removes/adds hydrogens by
oxidation/reduction. Usually require NAD+/NADH
or FAD/FADH2 as co-factors/co-substrates).
E. Isomerase: converts one isomer to another (i.e.
phosphoglucoisomerase,
triose
phosphate
isomerase)
F. Enolase: converts C=C group to alcohol. No
change in oxidation state.
G. Synthase: Usually an enzyme that combines two
things to make a new compound.
O
A
O
P O
O
CH2
O
OH
H
O
H2C
O
O
+
OH
OH
OH OH
Glucose
OH
OH OH
Glucose-6-P
O P O
O
Pi
NH2
NH2
H
B
N
N
O
O
H2C
O
O
O
O P O P O P O
O
O
O
OH
OH
OH OH
N
N
O
C
O H
OO
P O
H
O
O
O
O
OH
COOH
H
O
H
COOH
succinate
fumarate
O
P
O
OH
O
P
OH
O
O
O
O
dihydroxyacetone phosphate
F
O
glyceraldehyde-3-phosphate
COOH
H
COOH
+
H2O
H
COOH
H
H
H
OH
COOH
fumarate
malate
NH2
G
O
O P O P O
O
O
ADP
NH2
N
N
N
O
+
O
OH OH
N
N
N
O
O
O
O P O
O
O P O P O P O
O
O
O
Pi
ATP
N
N
O
OH OH
N
N
O
OH OH
H
H
O
ADP
(adenosine diphosphate)
O
O
O
O
O P O P O
O
O
Glucose-6-P
COOH
E
P O
O
CH2
O
OH
COOH
H
H
O
N
N
OH
2-phosphoglycerate
3-phosphoglycerate
D
P
O
OH
OH OH
OH OH
ATP
(adenosine triphosphate)
O
Glucose
O
O
2