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Lecture 1

Introduction to Metabolism

Metabolism
The sum of the chemical changes that
convert nutrients into energy and the
chemically complex products of cells.
Hundreds of enzyme reactions organized
into discrete pathways.
Substrates are transformed to products
via many specific intermediates.
Metabolic maps portray the reactions.
Intermediary metabolism.
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A Common Set of Pathways


Organisms show a marked similarity
in their major metabolic pathways.
Evidence that all life descended
from a common ancestral form.
There is also significant diversity.

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The Sun is Energy for Life


Phototrophs use light to drive
synthesis of organic molecules.
Heterotrophs use these as building
blocks.
CO2, O2, and H2O are recycled.

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Metabolism
Metabolism consists of catabolism
and anabolism
Catabolism: degradative pathways
Usually energy-yielding!

Anabolism: biosynthetic pathways


energy-requiring!

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Catabolism and Anabolism


Catabolic pathways converge to a
few end products.
Anabolic pathways diverge to
synthesize many biomolecules.
Some pathways serve both in
catabolism and anabolism.
Such pathways are amphibolic.
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Organization in Pathways

Pathways consist of sequential steps.


The enzymes may be separate.
Or may form a multienzyme complex.
Or may be a membrane-bound
system.
New research indicates that
multienzyme complexes are more
common than once thought.
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Multienzyme complex

Separate
enzymes

Membrane
Bound System
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Organization of Pathways
Closed Loop
(intermediates recycled)

Linear
(product of rxns
are substrates for
subsequent rxns)
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Spiral
(same set of
enzymes used
repeatedly)

Metabolism Proceeds in
Discrete Steps
Enzyme specificity defines
biosynthetic route.

Controls energy input and


output.
Allow for the establishment
of control points.
Allows for interaction
between pathways.

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Regulation of Metabolic Pathways

Pathways are regulated to allow the organism to


respond to changing conditions.
Most regulatory response occur in millisecond
time frames.
Most metabolic pathways are irreversible under
physiological conditions.
Regulation ensures unidirectional nature of
pathways.
Flow of material thru a pathway is referred to
as flux.
Flux is regulated by supply of substrates,
removal of products, and activity of enzymes

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Enzyme Regulation of Flux


Common mechanisms
Feedback inhibition product of pathway down
regulates activity of early step in pathway

Feedforward activation metabolite produced early in


pathway activates down stream enzyme.

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Metabolic Control Theory

Pathway flux is regulated by multiple


enzymes in a pathway.
Control coefficient determined for each
enzyme. = D activity / D enzyme
concentration.
Enzymes with large control coefficients
important to overall regulation.
Recent finding suggest that the control of
most pathways is shared by multiple
pathways enzymes.

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Regulating Related Catabolic and


Anabolic Pathways
Anabolic & catabolic pathways involving
the same compounds are not the same.
Some steps may be common to both.
Others must be different - to ensure
that each pathway is spontaneous.
This also allows regulation mechanisms to
turn one pathway and the other off.
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Metabolic Pathways are not at


Equilibrium
Metabolic pathways are not at equilibrium
A <-> B
Instead pathways are at steady state.
A -> B -> C
The rate of formation of B = rate of utilization of B.
Maintains concentration of B at constant level.
All pathway intermediates are in steady state.
Concentration of intermediates remains constant even
as flux changes.

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Thermodynamics and
Metabolism

Standard free energy A + B <-> C + D

DGo =-RT ln[C][D]/[A][B]

DGo = -RT ln Keq

DGo < 0 (Keq>1.0) Spontaneous forward rxn

DGo = 0 (Keq=1.0) Equilibrium

DGo > 0 (Keq <1.0) Rxn requires input of energy

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DG (not DGo) is important in vivo

DG = DGo + RT ln Q
Q (mass action ratio) = [C][D]/[A][B]
Actual [reactants] and [products] used to
determine Q.
Because reactions are at steady state not
equilibrium, Q does not equal Keq
When Q is close in value to Keq = near-equilibrium
rxn (reversible)

If Q is far from Keq = metabolically irreversible


rxn.
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ATP is the energy currency


of cells.
In phototrophs, light
energy is transformed into
the light energy of ATP.
In heterotrophs,
catabolism produces ATP,
which drives activities of
cells.
ATP cycle carries energy
from photosynthesis or
catabolism to the energyrequiring processes of
cells.
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ATP

Phosphoric Acid Anhydrides


ADP and ATP are
examples of phosphoric
acid anhydrides
Large negative free
energy change on
hydrolysis is due to:
electrostatic repulsion
stabilization of
products by ionization
and resonance
entropy factors
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Phosphoryl-group Transfer

Energy produced from a rxn can be coupled to


another rxn that requires energy to proceed.
Transfer of a phosphate group from high energy
phosphorylated compounds can activate a substrate
or intermediate of an energy requiring rxn.
A-P + ADP -> A + ATP, ATP +C-> ADP + C-P
The ability of a phosphorylated compound to
transfer a phosphoryl group is termed its
phosphoryl-group-transfer-potential.

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Phosphoryl-group Transfer

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