Transcript Metabolic pathways

Metabolic pathways
What do we mean by metabolism?
• Metabolism is the collective term for the
reactions that
thousands of biochemical _________
occur within a living cell.
enzymes
• These reactions are catalysed by __________
and are part of metabolic ____________.
pathways
A (very) simple metabolic pathway:
Substance 1
Substance 2
Enzyme 1
Substance 3
Enzyme 2
Intermediate
Substrate
__________
Product
__________
Metabolite
Enzyme 1
Enzyme 2
What do we mean by metabolism?
• Metabolism is the collective term for the
thousands of biochemical reactions that occur
within a living cell.
• Six characteristics of metabolic pathways:
• These pathways are integrated (i.e. connected), they do not
proceed in isolation.
• These pathways are tightly controlled.
• These pathways can have reversible and irreversible steps
• Metabolic pathways may exist that can bypass steps in a
pathway thereby providing alternative routes.
• Enzymes often act in groups or as multi-enzyme complexes.
DNA and RNA polymerases are part of multi-enzyme
complexes.
• There are two types of pathways
Types of metabolic pathways
• Anabolic pathways: involve biosynthetic
protein
processes (e.g. _________synthesis).
They
require energy.
__________
• Catabolic pathways: involve the breakdown of
respiration
molecules (e.g. ______________).
They
release energy.
__________
catabolic and
• Energy is transferred between __________
____________
pathways by ______.
anabolic
ATP
Glucose +
oxygen
Catabolic
pathway
CO2 +
water
Protein
ATP
Anabolic
pathway
Amino
acids
What do you remember about
enzymes?
• They are proteins and can be denatured at
high temperatures
• They speed up (i.e. catalyse) a chemical
reaction that transforms substrate(s) into
product(s) and do not get used up/ modified
in the process.
• They have an active site in which the substrate
binds.
Enzymes: activation energy
heat
• If there is enough _______energy
given to a
molecule, its chemical bonds will become
highly unstable.
transition
• This stage is called ___________state
• In the ___________state,
chemical bonds can
transition
broken
be ___________and
a chemical reaction can
take place.
• Can this heat energy be provided within cells for
chemical reactions to take place?
• NO!
• How can enzyme speed up reactions?
• Instead, the substrate(s) is being contorted by the
enzyme into a highly unstable state (i.e. transition
state) so that chemical bonds can be broken.
• The energy needed to contort the molecule into a
highly unstable state is referred to as ACTIVATION
energy.
Activation energy diagram
Enzymes lower the activation energy
needed for a reaction to take place
Summary
• Activation energy is the energy needed to contort
the molecule into a highly unstable state
(Transition state) so that chemical bonds can be
broken and a chemical reaction can take place.
• Out with cells, this energy is provided in the form
of heat energy.
• In cells, enzymes lower the activation energy
needed for a chemical reaction so that they can
take place at lower temperatures.
Enzymes: active site and induced fit
In N5: this was the story (not anymore!):
The active site of an enzyme is a groove or a hollow
created by the chemical structure of and the bonding
between the enzyme’s amino-acids.
The substrate shows affinity (chemical attraction) to
the active site.
The specificity of an enzyme is attributed to a
compatible fit between the shape of its active site and
that of its substrate.
• When the reaction involves 2 or more reactants,
the active site has a role in orientating reactants.
Active Site: summary
• What is an active site?
• The active site of an enzyme is a groove or a hollow created
by the chemical structure of and the bonding between the
enzyme’s amino-acids.
• Why does the substrate bind to the active site?
• The substrate shows affinity (chemical attraction) to the
active site.
• What the basis of the specificity of an enzyme?
• The specificity of an enzyme is attributed to a compatible
fit between the shape of its active site and that of its
substrate.
• When the reaction involves 2 or more reactants, what does
the active site do?
• the active site has a role in orientating reactants.
Induced fit
Induced fit
When the substrate enters the active site,
the shape of the active site and that of the
enzyme changes due to…………
Induced fit
When the substrate enters the active site,
the shape of the active site and that of the
enzyme changes …….due to chemical
interactions between the substrate and the
active site.
• This change in shape is called the
induce fit
______________and
it makes the active site
fit even more snuggly around
the___________.
substrate
• As a result, the conditions for the chemical
reaction to take place are optimized as the
activation
energy
_____________needed
to reach the
transition
lowered
___________state
is increased/lowered.
• Homework:
• Booklet, Qs p18: 1,2,5,6,7,9,10
• Book p85, Q1-2-3-4
Control of metabolic pathways
• Regulation can be controlled by intracellular
and extracellular signal molecules.
Control of metabolic pathways
What are the two types of genes that need to be regulated?
Genes only
expressed
sometimes e.g.
lipase to digest
fats
Genes always
expressed
e.g. enzymes for
respiration
Control of metabolic pathways
Genes only
expressed
sometimes e.g.
lipase to digest
fats
• How are genes from these metabolic pathways
controlled?
• Control by selective gene expression
• What does that mean?
• Genes coding for enzymes which are not always
needed can be switched on/off.
• Control of MP is by the presence or absence of a
particular enzymes.
Control of metabolic pathways
Genes always
expressed
e.g. enzymes for
respiration
• How are genes from these metabolic
pathways regulated?
• Control through the regulation of the rate of
reaction:
Are you sure that you understand the meaning of
the “rate of reaction?”
• Rate of reaction: change of concentration of a
substance per unit of time.
• Measured by either the decreasing
concentration of the substrate or the
increasing concentration of a product.
Extra bit
• The rate of reaction is the speed of a reaction,
i.e. how fast it happens.
• At a low rate of reaction, the reaction happens
slowly.
• At a high rate of reaction, the reaction
happens fast.
• A rate of reaction can increase (reactions
happen increasingly faster) or decrease
(reactions happen increasingly slower)
Control of metabolic pathways
Genes always
expressed
e.g. enzymes for
respiration
• The control through the regulation of the rate
of reaction can take place in three ways:
1- control by the concentration of
substrate/product
2- control through competitive and noncompetitive inhibitor
3- control through feedback inhibition
The effect of substrate concentration on the rate of reaction
B
A
1/ What is the limiting factor in A?
The effect of substrate concentration on the rate of reaction
B
A
1/ What is the limiting factor in A?
In A, the limiting factor is the substrate concentration
The effect of substrate concentration on the rate of reaction
B
A
2/ As the reaction stopped in B?
The effect of substrate concentration on the rate of reaction
B
A
2/ As the reaction stopped in B?
Not, the rate of reaction is high, in other words the
reaction takes place very quickly but at a steady rate.
The effect of substrate concentration on the rate of reaction
B
A
3/ What is the limiting factor in B? (Why does the rate of
reaction eventually stop increasing?)
The effect of substrate concentration on the rate of reaction
B
A
3/ What is the limiting factor in B? (Why does the rate of reaction
eventually stop increasing?)
The limiting factor in B is not substrate concentration, nor
temperature (enzymes are working at maximum rate), it has to be
enzyme concentration (all active sites are involved in the reaction)
or another sort of control such as feedback inhibition (see later).
Control of the rate of reaction
1- control by the concentration of
substrate/product.
The presence of a substrate or the removal of a
product will have an effect on both
– the rate of reaction
– drive a sequence of reactions in a particular
direction, i.e. towards equilibrium.
.
Most
enzymatic
reactions
are reversible
Extra bit: Understanding chemical
equilibrium
• When reversible reactions reach equilibrium the
forward and reverse reactions are still happening but
at the same rate, so the concentrations of reactants
and products do not change.
Extra bit: Do enzymes change
equilibrium?
• They don’t, they just make it happen faster.
Control of the rate of reaction
1- control by the concentration of
substrate/product
2- control through competitive and noncompetitive inhibitor
Competitive inhibitor
Competitive inhibitor
Inhibitor molecule binds to active site.
How can it be reversed?
Remember, it is a competition!
Competitive inhibitor
Competitive inhibition can be reversed by increasing
substrate concentration.
Non-Competitive inhibitors
• How do you think this may be different?
Non-Competitive inhibitors
• How do you think this may be different?
Non-Competitive inhibitors
• How do you think this may be different?
• Binding by the non-competitive inhibitor
changes shape of active site so that it is no
longer affinity to the substrate
A
B
Identify the type of inhibition with the graph
(competitive or non-competitive)
A
B
A is competitive (at high substrate concentrations, the inhibitor as little
effect on the rate of reaction)
B is non-competitive, the rate of reaction with the inhibitor remains
lower than without, independently of substrate concentration.
Control of the rate of reaction
1- control by the concentration of
substrate/product
2- control through competitive and noncompetitive inhibitor
3- control through feedback inhibition
Control through feedback inhibition
The end product binds to an enzyme that
catalyses a reaction early in the pathway and
inhibits its function.