Transcript 9. AH Cell Enzymes - charlestonbiology

Molecular interactions in cells
Many
Metabolic pathways (biochemical pathways)
Complex often series of enzyme controlled reactions
Energy transformed
Molecules degraded and synthesised
ATP - Adenosine Triphosphate
nucleic acid – adenine base, ribose sugar,
three phosphate groups
stores energy and makes it available
energy is used for chemical, transport and
mechanical work
Catalysis
Metabolism of an organism is the series of
complex biochemical reactions that occur
within them.
Reactions are sped up (catalysed) by enzymes.
Anabolic Reactions
• Uses energy to SYNTHESISE
large molecules from smaller
ones e.g.
Amino Acids
Proteins
• Also known as endothermic
reactions
ENDOTHERMIC REACTION
Catabolic Reactions
• These release energy
through the BREAKDOWN
of large molecules into
smaller units e.g.
Cellular Respiration:
ATP
ADP + Pi
• Also known as exothermic
reactions
EXOTHERMIC REACTION
Enzyme characteristics
made of protein
catalyse reactions
affected by temperature and pH
denatured at high temperature
are specific to a reaction because of their active
site.
Enzymes
All chemical reactions require energy to enable
them this is the activation energy.
Enzymes lower the activation energy.
2 types of reaction are:
Anabolic (synthesis) a dehydration synthesis
reaction.
Catabolic (degradation) a hydrolysis reaction.
Enzyme types
Proteases - break down proteins into amino acids
by breaking peptide bonds (hydrolysis).
Nucleases - break down nucleic acids into
nucleotides (hydrolysis).
Kinases - add phosphate groups to molecule.
Phosphatases – remove phosphate groups
ATPases - hydrolysis of ATP.
Enzyme activity
Active site is region where the reaction with substrate
occurs.
Correct substrate alters the shape of the active sight to
allow the substrate to fit perfectly.
This is called the 'induced fit model'.
(Molecules close to shape of substrate may react with
differing efficiencies)
Control of Enzyme activity
Control of enzyme activity occurs in these ways
number of enzyme molecules present
compartmentalisation
change of enzyme shape by
competitive inhibitors, non-competitive inhibitors,
enzyme modulators, covalent modification
end product inhibition
Competitive inhibition
A molecule close to shape of substrate competes
directly for active site so reducing the concentration
of available enzyme.
This can be reversed by increasing the concentration
of the correct substrate unless the binding of
competitor is irreversible.
Malonate example
Succinate dehydrogenase catalyses the oxidation of
succinate to fumarate (respiration)
Malonate is the competitive inhibitor
Non-competitive inhibition
An inhibitor binds to the enzyme molecule at a
different area and changes the shape of the
enzyme including the active site.
This may be a permanent alteration or may not.
•Inhibition can either be reversible or non-reversible
•Some inhibitors bind irreversibly with the enzyme
molecules.
•The enzymatic reactions will stop sooner or later and
are not affected by an increase in substrate
concentration.
•These are irreversible inhibitors heavy metal ions
including silver, mercury and lead ions.
Enzyme modulators
Some enzymes change their shape in response to a
regulating molecule.
These are called allosteric enzymes
Positive modulators (activators)
stabilise enzyme in the active form.
Negative modulators (inhibitors)
stabilise enzyme in the inactive form.
Allosteric Enzymes
Covalent modifications
Involves the addition, modification or removal of a
variety of chemical groups to or from an enzyme
(often phosphate.)
These result in a change in the shape of the enzyme
and so its activity.
These include phosphorylation by kinases and
dephosphorylation by phosphatases.
Conversion of inactive forms to active forms e.g.
trypsinogen and trypsin
An example of activation is trypsinogen to trypsin
trypsinogen activated by
enterokinase in duodenum
Trypsin is synthesised in the pancreas, but not in its
active form as it would digest the pancreatic tissue
•Therefore it is synthesised as a slightly longer
protein called TRYPSINOGEN
•Activation occurs when trypsinogen is cleaved by a
protease in the duodenum
•Once active, trypsin can activate more trypsinogen
molecule
An example of phosphorylation activating an
enzyme is the skeletal muscle enzyme
GLYCOGEN PHOSPHORYLASE
Glycogen is converted to glucose when heavy
demands are placed on muscle tissue
Glycogen phosphorylase must be activated when
sugar is needed and quickly deactivated when
glucose is plentiful.
Glucose and ATP act as negative modulators
AMP (adenosine monophosphate) acts as a positive
modulator
This is useful, because AMP is a product of ATP
breakdown and will be more plentiful when energy
levels are low and more glucose is needed
A further complication is that there is a hormonal
control mechanism by adrenaline and glucagon
End product Inhibition
Often seen in pathways that involve a series of
enzyme controlled reactions.
The end product once produced has an inhibiting
affect on an enzyme in the reaction.
Example:
Bacterial production of amino acid isoleucine from
threonine.
5 stages enzyme controlled
Threonine
Isoleucine
End-Product Inhibition
Metabolism is organised as a series of metabolic
pathways, and control of these pathways is an
important feature of cell biochemistry
End-product inhibition is energetically efficient
as it avoids the excessive (and wasteful)
production of the intermediates of a pathway
This is a form of NEGATIVE FEEDBACK
describe the catalytic functions of proteases,
nucleases, ATPases and kinases
describe the induced fit model of enzyme activity
explain how competitive and non-competitve inhibitors
affect enzyme activity
describe allosteric enzymes
explain the effect of positive and negative modulators
binding to allosteric enzymes
explain what is meant by covalent modification of
enzymes and how they control enzyme activity
explain the role of end-product inhibition in the control
of metabolic pathways