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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
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
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
Metabolism
• Metabolism consists of catabolism
and anabolism
• Catabolism: degradative pathways
– Usually energy-yielding!
• Anabolism: biosynthetic pathways
– energy-requiring!
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
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
Mutienzyme complex
Separate
enzymes
Membrane
Bound System
Organization of Pathways
Closed Loop
(intermediates recycled)
Linear
(product of rxns
are substrates for
subsequent rxns)
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
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
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
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 impt to
overall regulation.
• Recent finding suggest that the control of most
pathways is shared by multiple pathwayt
enzymes
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
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.
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
DG (not DGo’) is impt 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 = nearequilibrium rxn (reversible)
• If Q is far from Keq = metabolically
irreversible rxn.
• 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
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
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.
Phosphoryl-group Transfer