Chapter 6. Introduction to Metabolism.
Metabolism
Energy and Life.
Chemistry of life is
organized into metabolic pathways.
Organisms transform
energy.
Energy transformation is
governed by two laws of thermodynamics
Organisms live at the
expense of free energy.
ATP powers chemical
reactions by coupling exergonic reactions to endergonic reactions.
Enzymes.
Enzymes speed up
chemical reactions.
Enzymes are substrate
specific.
Active site is catalytic
center.
Cells
physical and chemical environment affects enzyme activity.
The
Control of Metabolism.
Metabolic control often
depends on allosteric regulation.
Enzyme localization
helps order metabolism.
Metabolism,
Energy and Life.
Metabolism is the total chemical activity of a living organism.
Arises from
interactions between molecules within the orderly cell environment.
Thousands of
reactions occur every instant.
Chemistry
of Life is organized into metabolic pathways.
Elaborate
and complex road map of the thousands of chemical reactions that take place
inside the cell (Fig 6.1).
Metabolism
is concerned with managing the material and energy recourses of the cell.
Breaking
things down to release subunits and energy or building complex molecules
(macromolecules) and using energy.
Two basic
types of reactions:
Catabolic reactions-breakdown complex molecules into simpler ones releasing energy.
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Anabolic reactions link together simple molecules to form complex molecules storing
energy in chemical bonds.
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Protein synthesis from
amino acids.
Organisms
transform energy.
Two basic
types of energy are kinetic and potential.
Kinetic energy
is the energy of action.
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Energy that does work,
(alters the state or motion of matter) can exist as heat, light, electric and
mechanical.
Potential energy is the energy of state or position.
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Stored energy: chemical
bonds, concentration gradients and electrical potentials are all important in
biology.
Energy
transformations of life are subject to two laws of thermodynamics.
First Law
of Thermodynamics: Energy is neither created or destroyed it just changes
forms (transformed).
Second
Law of Thermodynamics: Not all energy is used and disorder tends to
increase (entropy increases).
An organism can increase its order at the expense of
the order around it (Fig 6.4).
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When energy is created some is unavailable to do work.
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No reaction is 100%
efficient (heat).
Organisms
live at the expense of free energy.
Reactions
that proceed without energy input are considered spontaneous while those
that do not proceed without an energy input are considered nonspontaneous.
Free
energy (G) is the portion of a systems energy that can perform work when temperature
is uniform throughout.
Free because it is available to do work (Fig. 6.5).
Total energy is called enthalpy (H), unusable
energy is entropy (S).
This is affected by absolute temperature
(T), in Kelvin (K) (K = oC + 273).
We are interested in the change in free energy
therefore the equation is DG=DH-TDS, from a starting state to ending state.
This equation indicates whether free energy is
released or consumed by a chemical reaction (Fig 6.6).
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-DG = energy released (exergonic), considered
spontaneous.
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+DG = energy consumed (endergonic), considered
nonspontaneous
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We will be able to
follow the release or consumption of energy during chemical reactions by
following the change (D) in free energy (G).
Ex: Exergonic reaction (cellular respiration):
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C6H12O6
+ 6O2 ΰ 6CO2 + 6H2O; DG = -686 kcal/mol
(-2870 kJ/mol).
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For every mole of
glucose (186 g) broken down by respiration 686 kcal of energy are made
available (released) for work.
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Reverse of this would be
photosynthesis and would cost 686 kcal (+686 kcal/mole glucose made, powered
by light energy).
If a reaction runs spontaneously from reactant A ΰ product B then the reverse (B ΰ A) requires energy.
At some concentration of A and B; the forward and
reverse reactions take place at the same rate this is a chemical equilibrium
(DG = 0).
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No observable change in
the system, even though individual reactions are still occurring.
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The idea
of free energy change and
thermodynamics are important for understanding how cells function, specifically
how biochemical reactions occur.
Exergonic reactions drive endergonic reactions (energy
coupling), a small molecule (ATP) is responsible for mediating most
energy coupling in cells.
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This will be important
when we discuss how energy is made in cells.
ATP
powers cellular work by coupling exergonic reactions to endergonic reactions.
Adenosine
triphosphate or ATP is the energy form in the cell used for action.
Consists
of the nitrogenous base adenine fused to ribose which has three phosphates (not
one) attached (Fig 6.8).
Hydrolysis of ATP yields adenosine diphosphate
(ADP) and an inorganic phosphate ion (Pi = HPO2-4)
as well as free energy (DG = -13 kcal/mol or 50 kj/mol ( -7.3/-30 under lab
conditions)).
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The equilibrium is far to
the right (products) at equilibrium there is ten million times as much ADP as
ATP, ATP is continuously regenerated (Fig 6.10).
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Why is there more energy
in the P-P bonds?
ATP couples
exergonic and endergonic reactions.
Many enzyme-catalyzed reactions (exergonic) can
provide the energy to convert ADP to ATP (cellular respiration).
The
breakdown of this ATP then yields energy for other reactions (Fig 6.9).
Can be through a phosphorylated intermediate.
ATP lasts
less than one minute in the cell and on average 40 kg of ATP per day is
produced by a person at rest.
Enzymes:
Biological Catalysts.
DG may indicate how far the reaction proceeds
to completion but does not indicate the speed of the reaction.
Exergonic
reactions may be fast or slow.
Ex: Sucrose hydrolysis
is spontaneous but will happen imperceptibly until the enzyme sucrase is
added.
Enzymes (biological catalysts) speed up metabolic
reactions by lowering energy barriers.
A
catalyst is any substance that speeds up a reaction.
Most
biological catalysts are proteins called enzymes.
There are also RNA enzymes called ribozymes (Ch.
17).
Energy
barriers must be overcome for a reaction to proceed.
Includes breaking and reforming of chemical bonds.
Ex: Sucrose hydrolysis requires breaking the chemical bond
between glucose and fructose then forming water from H+ and OH-.
The energy
barrier represents the amount of energy needed to start the reaction, the activation
energy (EA) (Fig 6.12).
The activation energy moves the reactants from stable
to unstable, a state called the transition state.
Exergonic reactions need very little activation energy
while endergonic reactions need more.
The activation energy is often recovered so it does
not affect the DG.
Enzymes act to lower the activation energy, however, they
have no effect on equilibrium or DG.
Enzymes
are substrate specific.
Non-biological
catalysts do not show specificity like protein enzymes do.
Reactants
are substrates and they bind to the active site of an enzyme.
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Specificity results
from the 3-dimensional structure of the enzyme and substrate.
E + S ΰ ES ΰ E + P.
This active site is not rigid, the substrate can cause
the enzyme to change the shape of its active site, induced fit.
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Ex: Like a handshake.
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Ex: Hexokinase uses this
model for fitting around its substrate glucose.
Some active sites are more rigid and they fit like a
lock and key (lock and key model).
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Ex: The active site of
lysozyme neatly fits its substrate.
Enzymes use
the following mechanisms in order to change a reactant to a product: Orientation
of substrates, add charges to substrates or induce strain.
A
cells physical and chemical environment affects enzyme activity.
Enzyme
activity can be altered by environment (Ex: temp. and pH), chemicals and
concentration of substrate.
Substrate
concentration will affect reaction rate.
The more substrate the more possible collisions which
leads to more reactions per unit time (reaction rate).
Eventually in an enzyme catalyzed reaction, the enzyme
becomes saturated at a certain substrate concentration and rate levels
off.
Some enzymes
require added molecules for function.
Cofactors
are inorganic ions (copper, zinc and iron) that bind temporarily to enzymes and
are essential for function.
Inhibitors
of enzyme function can act reversibly or irreversibly (Fig 6.17).
Irreversible inhibition occurs when an inhibitor binds via a covalent bond
(often at the active site).
Reversible inhibition can occur at the active site (competitive
inhibition) or at a second site on the enzyme (noncompetitive inhibition).
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Competitive
inhibition occurs when the inhibitor
and substrate compete for the same active site.
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Noncompetitive
inhibition occurs when the inhibitor
binds outside the active site but in doing so renders the active site ineffective.
Enzymes are affected by
environmental conditions (Fig 6.16).
pH, temperature
and salinity can affect the function of an enzyme.
The Control of
Metabolism.
Metabolism
must be regulated in order to maintain homeostasis.
Metabolism
is therefore organized into pathways: A
+ an enzyme yields B; B + an enzyme yields C and so on.
Enzymes can
be regulated by their own production (gene level) or by enzyme activity.
Metabolic
control often depends on allosteric regulation (Fig 6.18).
Allosteric
enzymes (made of subunits) have a different response to substrate concentration
then other enzymes, they respond to fluctuating levels of regulators.
Allosteric
enzymes have a catalytic subunit and a regulatory subunit giving
extreme levels of control.
Feedback
inhibition (common) is the switching off of a metabolic pathway due to the
production of its end product (Fig 6.19).
Cooperativity
(Fig 6.20)is similar to allosteric activation in that binding of one
substrate stimulates catalytic activity.
Binding
may change the conformation of the other subunits and may amplify the response.
Cells
are not just bags of enzymes there are specific compartments for specific
enzymes as we saw in Chapter 7.