Chapter 15
15.1, 15.2, 15.4 (some)
Ying & Yang of Metabolism
Metabolism = Anabolism + Catabolism
Photosynthesis requires Respiration
Respiration requires Photosynthesis
Energy Production = Energy Consumption
Metabolism: breakdown and build up (synthesis)
Breakdown: Catabolism
Proteins to Amino Acids, Starch to Glucose, DNA/RNA to nucleotides
Synthesis: Anabolism
Amino Acids to Proteins, Glucose to Starch nucleotides to DNA/RNA
Metabolic Pathways
Two broad classes:
1. Those that convert energy into biologically useful forms are
called, catabolic pathways
Fuels (carbs & fats)  CO2 + H2O + useful energy:
catabolism
2. Those that require inputs of energy to proceed are called,
anabolic pathways
Useful energy + small molecules  complex molecules:
anabolism
Pathways that can be either anabolic or catabolic are referred to
as amphibolic pathways
Metabolic Pathways
The biochemical reactions in the living cell — the metabolism — is
organized into metabolic pathways
The pathways have dedicated purposes
Some are dedicated to extraction of energy
Some are dedicated to storage of fuels
Some are dedicated for synthesis of important building blocks
Some are dedicated to elimination of waste materials
The pathways can be represented as a map
Follow the fate of metabolites and building blocks
Identify enzymes that act on these metabolites
Identify points and agents of regulation
Identify sources of metabolic diseases
Homeostasis
Organisms maintain homeostasis by keeping the concentrations
of most metabolites at steady state
After brief adaptation, single-celled organisms (yeast and
bacteria) exhibit balanced, exponential, steady-state growth where
molecular proportions are maintained over large ranges of cell
density
In steady state, the rate of synthesis of a metabolite equals the
rate of breakdown of this metabolite
Cells maintain a dynamic steady state
As conditions change levels of intermediates stay close to the
same
Internal. Changes in amounts of fuel (ATP) regulate
the speed of processing
External. Remote changes sensed via hormones and
other messengers, change the levels of processing
Factors that Determine the Activity of Enzymes
Michaelis Menten Kinetics -- simplest case
for substrate effects
Reaction rates depend
on substrate
concentrations
according to enzyme
binding and turnover
characteristics
Usually it is a
rate limiting
step, one of the
1st few steps
Feedback inhibition
Feedback inhibition: (end product inhibition)
a late or final product of a multi-step pathway
inhibits an early enzyme in the pathway
(almost always at rate-limiting step).
Here, E1 is inhibited by isoleucine
(allosterically)
Only isoleucine inhibits E1 – none of the
other intermediates do
Isoleucine inhibits only E1 – not any of
the other enzymes (E2 – E5)
Feedback control
E1
A
E2
B
E3
C
E4
D
E
E4
D
A
E1
B
E2
E5
E
E6
F
G
E3
C
E7
E8
K
E9
L
E10
M
N
Metabolic Pathways
20
We Need Energy!
What do we do? move muscles, eat food, think, etc.
All of these activities are based upon chemical reactions, non spontaneous
reactions! To overcome a positive free energy, DG we need some other source
of free energy.
We need some sort of "free-energy currency,"
How about a molecule that can store and release free energy when it is
needed to power a given biochemical reaction?????
How “Free-Energy Currency” Works
Coupled reactions: separate chemical reactions may be added together to form
a net reaction.
DG for the net reaction = sum of the free-energy changes for the individual
reactions
Ex: phosphorylation of glycerol two reactions: the phosphorylation of glycerol the
dephosphorylation of ATP
Glycerol + HPO42- --> (Glycerol-3-P)2- + H2O
+
ATP4- + H2O --> ADP3- + HPO42- + H+
DGo'= +9.2 kJ (nonspontaneous)
Glycerol + ATP4- --> (Glycerol-3-P)2- +ADP3- + H+
DGo' = -21.3 kJ (spontaneous)
DGo' = -30.5 kJ (spontaneous)
dephosphorylation of ATP is spontaneous (DGo = -30.5 kJ) is often coupled with
nonspontaneous reactions to drive them forward.
The body's use of ATP as a free-energy currency is a very effective strategy to
cause vital nonspontaneous reactions to occur.
Free-Energy
DG Gibbs Free energy
DGo Standard Gibbs Free energy
DGo’ Standard Gibbs Free energy at pH = 7
Coupling favorable & unfavorable reactions
A pathway must satisfy minimally two criteria:
1. The individual reactions must be specific, yielding only one
particular product or set of products.
Enzymes provide specificity
2. The entire set of reactions in a pathway must be
thermodynamically favored
A reaction can occur spontaneously only if DG, the change in
free energy, is negative
The overall free energy change for a chemically coupled series
of reactions is equal to the sum of the free-energy changes of
the individual steps
Coupling favorable & unfavorable reactions
AB+C
DG0’ = + 5 kcal mol-1
BD
DG0’ = - 8 kcal mol-1
*******************************************
AC+D
DG0’ = - 3 kcal mol-1
ATP is the universal currency of free energy
Metabolism is facilitated by the use of a common energy currency
Part of the free energy derived from the oxidation of foodstuffs
and from light is transformed into ATP - the energy currency
A large amount of free energy is liberated when ATP is hydrolyzed to ADP &
Pi, or ATP to AMP & PPi
ATP + H2O  ADP + Pi
ATP + H2O  AMP + PPi
DG0’ = -7.3 kcal mol-1
DG0’ = -10.9 kcal mol-1
Under typical cellular conditions, the actual DG for these hydrolyses is
approximately -12 kcal mol-1 or 30.5KJ/mol
ATP hydrolysis drives metabolism by shifting the equilibrium of coupled
reactions: by a factor of approximately 108
In a typical cell, an ATP molecule is used within a
minute of its formation.
During strenuous exercise, the rate of utilization of
ATP is even higher. So the supply of ATP must be
regenerated.
We consume food to provide energy for the body,
but the majority of the energy in food is not in the
form of ATP.
The body utilizes energy from other nutrients in the
diet to produce ATP through oxidation-reduction
reactions
Structures of ATP, ADP,& AMP
ATP high phosphoryl potential
Ex: phosphorylation of by two molecules: the phosphorylation of glycerol the
dephosphorylation of ATP
Glycerol-3-P + H2O --> Glycerol + HPO42-
DGo'= -9.2 kJ
ATP4- + H2O --> ADP3- + HPO42- + H+
DGo'= -30.5 kJ
Magnitude of DG dephosphorylation of ATP is much more spontaneous
(DGo'= -30.5 kJ) is than Glycerol 3P, has more tendency to transfer phosphate.
The body's use of ATP as a free-energy currency is a very effective strategy to
cause vital nonspontaneous reactions to occur.
ATP
ATP is an energy-rich molecule because its triphosphate unit
contains two phosphoanhydride bonds ( & )
ATP has a high phosphoryl-group transfer potential
Resonance structures of orthophosphate
Why does ATP have a high phosphoryl transfer potential?
DG0’ depends on the difference in free energies of products and
reactants, therefore, both must be considered
Three factors are important:
1. Resonance stabilization: ADP Pi have more stable resonance
2. Electrostatic repulsion: 4 negative charges so close!
3. Stabilization due to hydration: H2O prefers to surround ADP and Pi
Other Compounds with high phosphoryl transfer
potential
Phosphoryl transfer potential
is an important form of
cellular energy transformation
These compounds can
transfer a phosphoryl group
to ADP to form ATP
They couple carbon oxidation
to ATP synthesis
Intermediate position of ATP
enables ATP to function efficiently as a carrier of phosphoryl groups

Sources of ATP during exercise
16
In resting muscle, [ATP] = 4 mM, [creatine phosphate] = 25 mM
[ATP] sufficient to sustain 1second of muscle contraction
ATP-ADP cycle
100g of ATP in the body,
turnover is very high.
Resting human consumes
40 kg of ATP in 24 hours.
Strenuous exertion:
0.5 kg / minute.
2hr run: 60kg utilized
The oxidation of carbon
fuels is an important
source of cellular energy
AMP is a sensitive
indicator of Cellular
Energy Capacity
Glucose: chemical bonds are broken, free energy is released
The complete breakdown of glucose into CO2 occurs in two
processes:
glycolysis and the citric-acid cycle
But glycolysis and the citric-acid cycle produce a net total of only
four ATP or GTP molecules (GTP is an energy-currency molecule
similar to ATP) per glucose molecule.
This ATP yield is far below the amount needed by the body for
normal functioning, and in fact is far below the actual ATP yield
for glucose in aerobic organisms (organisms that use molecular
oxygen).
For each glucose molecule the body processes, the body
actually gains approximately 30 ATP molecules!
So, how does the body generate ATP?
oxidative phosphorylation
NADH and FADH2. are molecules that are oxidized (i.e., give up
electrons) spontaneously.
The body uses these reducing agents (NADH and FADH2) in an
oxidation-reduction reaction and it is the free energy from these redox
reactions that is used to drive the production of ATP.
To make ATP, energy
supplied by the food we eat
must be absorbed.
This energy is used to
synthesize reducing agents
NADH and FADH2
NADH and FADH2 are
needed to produce ATP.
oxidative phosphorylation: oxidation of NADH; reaction coupled to a
phosphorylation of ADP the reduction reaction (gaining of electrons) that
accompanies the oxidation of NADH. In this case, molecular oxygen
(O2) is the electron acceptor
phosphorylation
ADP3- + HPO42- + H+ --> ATP4- + H2O DGo= +30.5 kJ
(nonspontaneous)
oxidation
NADH --> NAD+ + H+ + 2e- DGo= -158.2 kJ (spontaneous)
reduction
1/2 O2 + 2H+ + 2e- --> H2O DGo= -61.9 kJ (spontaneous)
Net reaction
ADP3- + HPO42- + NADH + 1/2 O2 + 2H+ --> ATP4- + NAD+ + 2 H2O
DGo= -189.6 kJ (spontaneous)
cells use oxygen (to oxidize NADH) after the break down the glucose
and store its energy in molecules of ATP.
the energy in glucose cannot be used by cells until it is stored in ATP
Without oxygen, cellular respiration could not occur because oxygen
serves as the final electron acceptor in the electron transport system.
The electron transport system would therefore not be available.
Overview of respiration
You need:
1. Source of Energy
Phototroph: light
Chemotroph: compounds
2. Source of Electrons
3. Carrier of Electrons
molecules that accept electrons from electron donors and donate them
to electron acceptors, creating an energy-producing electron transport
chain
4. Final Electron Acceptor
The Metabolic Pathway of Cellular Respiration
Cellular respiration is the process breaking down food
molecules (ex glucose) CO2 and H2O.
Why??.... So we can release the energy released that keeps
food molecules together is trapped in the form of ATP
ATP is used for all energy-consuming activities of the cell
Name some
The Metabolic Pathway of Cellular Respiration
Cellular respiration is an example of a
metabolic pathway: A series of chemical
reactions in cells –building or degradation
process
Enzymatic pathways: series of dependent chemical reactions.
The end product depends on the successful completion of five
reactions, each mediated by a specific enzyme.
The enzymes usually located close to each other... in an organelle or in
the membrane of an organelle make fast
Intermediate products tend not to accumulate equilibrium effects
minimized
The Metabolic Pathway of Cellular Respiration
All of the reactions involved in cellular respiration can be
grouped into two phases
Glycolysis: the breakdown of glucose to pyruvic acid
The Krebs cycle and Electron transport: the complete
oxidation of pyruvic acid to carbon dioxide and water
A Road Map for Cellular Respiration
Cytosol
Mitochondrion
High-energy
electrons
carried
mainly by
NADH
High-energy
electrons
carried
by NADH
Glycolysis
2
Glucose
Pyruvic
acid
Krebs
Cycle
Electron
Transport
Energy will be stored in form of
ATP (potential) energy
Bond breaking of ATP  ADP + Pi
will create energy (kinetic energy)
Energy Storage
Cellular Respiration
C6H12 O6 + 6O2 6H2O + 6CO2 + 38 ATP
Photosynthesis
6H2O + 6CO2 + light  C6H12 O6 + 6O2
Nitrification
NH4  NO2 to NO3
Ammonia to Nitrite to Nitrate
Ammonification
N2  NH4
Energy Storage
Cellular Respiration
C6H12 O6 + 6O2 6H2O + 6CO2 + 38 ATP
Photosynthesis
6H2O + 6CO2 + light  C6H12 O6 + 6O2
Nitrification
NH4  NO2 to NO3
Ammonia to Nitrite to Nitrate
Ammonification
N2  NH4
Respiration
Overview
– O2 and glucose to CO2 + H2O + energy($$)
– C6H12O6 + O2  6CO2 + 6H2O + 38 ATP
– Glucose is highly reduced; contains energy
– Oxygen receives the electrons to form energy
4 separate reactions
– Glycolysis, Transition Reaction, Krebs Cycle, Electron
Transport,
Requires Oxygen at end!
Glucose
Oxygen
Carbon
dioxide
Water
Energy
Steps in Respiration
Electron Donors
– Organic Compounds (Glucose preferred)
Electron Carriers
– NAD to NADH
– FAD to FADH
Electron Acceptors-Terminal
– O2 to H2O
Phosphorylation Reactions
– ADP to ATP
Recurring motifs in metabolic pathways
Unifying themes include, common metabolites, reactions, and
regulatory schemes.
Activated carriers exemplify modular design and economy of
metabolism, eg ATP is an activated carrier of phosphoryl groups
1. Activated carriers of electrons for fuel oxidation
NAD+ / NADH and FAD / FADH2
2. An activated carrier of electrons for reductive biosynthesis
NADP+ / NADPH
3. An activated carrier of two-carbon fragments
CoenzymeA, eg Acetyl CoA
Structure of nicotinamide-derived electron
carriers
Oxidized
forms
Nicotinamide adenine
dinucleotide (NAD+),
R=H
Nicotinamide adenine
dinucleotide
phosphate (NADP+),
R = PO32Prominent carriers of
high-energy electrons
Reaction type for NAD+ as electron acceptor
Structure of flavin adenine dinucleotide (FAD)
Oxidized form
Isoalloxazine ring of riboflavin
Electron carrier,
accepts 2 electrons,
& 2 protons
FMN
AMP
57
Reaction type for FAD as electron
acceptor
Electrons & protons carried by isoalloxazine ring
FAD
FADH2
Coenzyme A
Activated carrier of two-carbon fragments
Acyl groups linked to CoA by thioester bonds: high acyl grouptransfer potential (transfer is exergonic)
Acetyl CoA carries an activated acetyl group just like ATP carries
an activated phosphoryl group
Structure of Coenzyme A
B vitamin
Activated carriers

A small set of carriers responsible for most interchanges
of activated groups in metabolism
Thousands of metabolic reactions: down
to 6 types
1. Oxidation-reduction reactions
The two reactions are components of the citric acid cycle, which
completely oxidizes the activated two-carbon fragment of
acetyl CoA to two molecules of CO2
Oxidation of succinate & malate generates useful energy by
transferring electrons to carriers FAD & NAD+
2. Ligation reactions
Form bonds by using energy from ATP cleavage
Oxaloacetate can be used in the citric acid cycle, or converted
into amino acids such as aspartic acid
3.Isomerization reactions
Rearrange particular atoms within the molecule, often
in preparation for subsequent reactions, eg. oxidation-reduction
Component of citric acid cycle. Hydroxyl group of citrate moved
from tertiary to secondary position followed by oxidation-reduction
and decarboxylation
4. Group transfer reactions
Play a variety of roles. eg. phosphoryl group transfer to glucose
Reaction traps glucose
in the cell
67
5. Hydrolytic reactions
Cleave bonds by the addition of water:
common means employed to break down large molecules
6. The addition of functional groups
covalent cat
To double bonds or the removal of groups to form double bonds,
catalyzed by lyases. Example from glycolysis in reaction (7)
Glycolysis
Most completely understood
biochemical pathway
Plays a key role in energy
metabolism by providing
significant portion of energy
utilized by most organisms
Splits the 6-C sugar (glycolysis)
Generates two molecules of
ATP per molecule of glucose
Converts two NAD+ to NADH
per molecule of glucose
Ethanol Fermentation
Lactic Acid Fermentation
Fermentation of glucose to
ethanol:
Wine making & baking both
exploit this process
From Lehninger
Principles of Biochemistry
2 Pyruvic acid
Glucose
Figure 6.8
The types of reactions occurring in glycolysis:
1)phosphoryl transfer: kinase
2) phosphoryl shift: mutase
3) isomerization: isomerase
4) dehydration: dehydratase
5) aldol cleavage: aldolase
6 CH OPO 2
2
3
5
O
H
4
OH
H
OH
3
H
H
2
H
1
OH
OH
glucose-6-phosphate
Glycolysis takes place in the cytosol of cells.
Glucose enters the Glycolysis pathway by conversion to
glucose-6-phosphate.
Initially there is energy input corresponding to cleavage
of two ~P bonds of ATP.