Download L1 - Enzymes and Biological Regulation

Enzymes and Biological Regulation
Enzyme Characteristics
• Enzymes are proteins that catalyze chemical
reactions. They speed up chemical reactions
by lowering activation energies.
Enzyme Characteristics, cont.
• Most enzymes are proteins.
• Enzymes are specific in the type of
reactions they catalyze.
1. Absolute specificity – acts only on one
substance.
2. Relative specificity – acts on
structurally related substances.
3. Stereochemical specificity –
distinguishes between stereoisomers.
Classifying and Naming Enzymes
Enzyme Characteristics, cont.
• Their activity can be regulated.
• There are approximately 3000 enzymes
per cell
• Common enzymes we have seen:
1. Lactase – digests lactose into glucose and
fructose
2. Maltase – hydrolysis of maltose to glucose for
yeast alcohol production.
3. Protease – breaks peptide linkages to form
protein segments in amino acid sequencing.
Classifying and Naming Enzymes, cont.
• A substrate is the substance that undergoes a
chemical change catalyzed by an enzyme.
• Enzyme names are based on the substrate or
type of reaction and adding –ase ending
Reference
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Enzymatic Processes
• All enzymes have an active site – the
location on the enzyme where a
substrate binds and catalysis occurs.
• Enzymes complex with the substrate and
the chemical reaction proceeds.
Enzymatic Processes, cont.
The active
site of an
enzyme is
usually a
crevice-like
region formed
as the result of
the protein’s
secondary and
tertiary
structural
characteristics.
Enzymatic Processes, cont.
There are two main theories on active sites:
1. Lock-and-key theory – the substrate has a
shape that exactly fits the active site. This
explains enzyme specificity.
Enzymatic Processes, cont.
2. Induced-fit theory – the conformation
of the active site changes to
accommodate an incoming substrate.
Enzyme Regulation
Enzyme regulation refers to the
biological processes that control the
ability of enzymes to catalyze reactions.
Controls include:
1.Presence of cofactors
2.Inhibition
3.Induction/degradation
4.Modulation (Allosteric Regulation)
5.Zymogen activation
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Enzyme Regulation, cont.
1. Enzyme Cofactors
•Some enzymes require a second substance
present (cofactor) in order to be active.
•Cofactors can be metal ions or a nonprotein molecule
–If the cofactor is an organic molecule,
the cofactor is called a coenzyme.
•Coenzymes are often derived from
vitamins.
Enzyme Regulation, cont.
2. Enzyme Inhibition
•Inhibitors decrease enzyme activity.
•Irreversible inhibitors covalently bond
with the enzyme and render it inactive.
Many poisons are irreversible
inhibitors.
Examples: CN-, Hg2+, Pb2+
Some antibiotics are irreversible
inhibitors.
Enzyme Inhibition, cont.
Competitive
inhibition can
be reversed by
increasing
substrate
concentration
(LeChatlier’s
principle).
Enzyme Cofactors, cont.
• An apoenzyme is the catalytically inactive
protein formed by the removal of the
cofactor.
• The biologically active protein formed by the
presence of a cofactor is called a haloenzyme
–The ES complex can not exist with out
the cofactor.
Enzyme Inhibition, cont.
• Reversible inhibitors reversibly bind with
enzymes.
• Types of reversible inhibitors:
1. Competitive reversible inhibitors
- compete with substrate for binding at
active site.
2. Noncompetitive reversible inhibitors
- bind to the enzyme at a location other
than the active site.
(form of modulation)
Enzyme Inhibition, cont.
Substrate concentration doesn’t affect
inhibitor action in non-cometitive
inhibition.
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Enzyme Inhibition, cont.
Heavy metal poisoning is an example of
noncompetitive inhibition of an enzyme.
Enzyme Inhibition, cont.
•Feedback inhibition is a form of competitive
inhibition where the molecule produced by
the catalysis of many reactions results in an
inhibitor to an earlier catalyzed reaction.
Enzyme Regulation, cont.
3.Induction/ Degradation
• Form of Genetic control
• Induction refers to the body’s synthesis of
enzymes in response to cellular need.
• Degradation is the subsequent hydrolysis of
enzymes to amino acid or peptide residues.
Biological systems usually utilize
induction/degradation for enzymes needed only for
temporary use due to the inefficiency of the control.
Induction/ Degradation, cont.
Enzyme Regulation, cont.
• Example of Enzyme Induction:
4. Modulation
– Synthesis of β-galactosidase in bacterium.
– Escherichia coli (E. coli) produce β-galactosidase
as needed for the hydrolysis.
– When there is an absence of lactose, the bacteria
stops producing the enzyme
• Modulation, also called allosteric regulation,
refers to the binding of a chemical species to a
binding site other than the active site to control
enzyme activity
•Enzymes containing a secondary binding site,
or modulator binding site, are called allosteric
enzymes.
•Modulation may be positive or negative
•Positive modulators increase activity by
changing the shape of the active site to allow
the ES complex.
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Modulation, cont.
•Negative modulators (seen here) decrease
activity by changing the shape of the active
site to prevent the ES complex.
Enzyme Regulation, cont.
5. Zymogen activation
• Zymogens – an inactive precursor
(proenzyme) of an enzyme.
– Some enzymes are stored as inactive
zymogens.
– Released when needed and activated at
the location where the reaction occurs
by either an activation agent or by
autoactivation.
Zymogen activation, cont.
•An example of activation occurs when
chymotrypsinogen (in the pancreas) is
activated by the presence of trypsin in the
small intestine resulting in the chymotrypsin
enzyme.
Modulation, cont.
•Feedback inhibition is an example of a
modulator decreasing an allosteric enzyme’s
activity.
Zymogen activation, cont.
•Autoactivation can also occur as the zymogen
is introduced to a chemical species or
physiological environment that allows the
formation of the proteins native state.
•Activation can also occur in the presence of a
chemical species due to the resulting changes
in the IM forces and 3o,4o structure.
Zymogen activation, cont.
•Activation may also occur by the addition or
removal of a section of protein catalyzed by
an activation enzyme (or activation agent)
* [notice the –ogen suffix
of the proenzme]
Chymotrypsinogen
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Zymogen activation, cont.
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