Mechanisms of

Enzyme Regulation
Substrate
concentration
Reversible inhibition
by
products or other
compounds Allosteric
activation or inhibition
Proteolytic
cleavage
Covalent
modification
Modulator protein
binding
Amount of enzyme
present

Covalent
3.
Proteolytic
cleavage.
Certain
Substrate
Allosteric
regulation
of
metabolic
modification
enzymes
synthesized
as
1.
influence.are
pathways.
The
activity of enzymes
The
rates of most
enzymes
are
proenzymes,
or
zymogens,
Phosphorylati
that
key
regulatory
a. catalyze
Effecttoon
enzyme
activity.
In
responsive
changes
in
substrate
on
which
are(committed
inactive
forms
of of of a
reactions
steps)
certain
enzymes,
the
addition
concentration because the
enzymes
that
become
active
only
metabolic
pathways
are
often
subject
phosphate
group
to
a
specific
intracellular level of many substrates
after
being
cleaved
at[usually
aThus,
specific
amino
acid
serine
to
allosteric
regulation.
Their
activity
is in
the
range
ofresidue
the K
.
an
m
(Ser),
tyrosine
(Tyr),
orchain
threonine
site
in
their
polypeptide
by
can
be
modulated
by
the
binding
increase
in
substrate
concentration
a. Many
digestive
enzymes
(Thr)]
by
specific
protein
specific
proteases.
of
allosteric
effectors
to a kinases
siterate,
on
prompts
an
increase
in
reaction
that
hydrolyze
proteins
dramatically
enhances
or
the
enzyme
that
is
distinct
from
the
which
tends
to
return
the
1. (e.g.,
Effectors
are
positive
if
they
trypsin,
pepsin)
are product
depresses
activity.
Product
inhibition.
If
the
active
site
(i.e.,
allosteric
site).
concentration
ofas
substrate
toward
enhance
the
rate
ofzymogens
a reaction
(i.e.,
b.
synthesized
This
modification
is
reversible.
in some
accumulates,
it
can
inhibit
normal.
activators)
and
negative
if they
The
phosphorylated
enzyme
may
the
stomach
and
pancreas.
enzymes.
This
form
of control
2.
decrease
the
rateofof formation
reaction
(i.e.,
bethe
dephosphorylated
by specific
b. Blood
clotting
is mediated
limits
rate
of the
Nucleotidylati
a. phosphatases.
Effect on enzyme activity. The
inhibitors).
on by
product
when
the is
product
is
2.
Feedback
inhibition
negative
a
series
of
proteolytic
activities of certain enzymes are
underused.
Besides
youstep of
can
modulation
ofactivities
the
committed
zymogen
of several
regulated
by
the
reversible
remember
that
Enzymes
do not
a
metabolic
pathway
by its end
serum
enzymes
addition
of a nucleotide
(e.g.,
affect
equilibrium
constants.
It
product.
This prevents
unnecessary
adenosine)
to a specific
amino
means
increasing
production
of an excess
of end product
acid. that
concentration
causes
to
increasing
product
by modification
shutting
down
b. This
isthe
reverse
reaction
and
decreasing
pathway
until
more
needed.
reversible.
Foris
example,
an
substrate
formation.
adenylated
enzyme may be
deadenylated by a specific
enzyme.

Use enzymes
as
analytical
Principal
serum
enzymes
used
in
clinical
ISOENZYMES
(ALSOcleavage
CALLED of enzyme
Enzymes as diagnostic
The
partial
Serum
enzyme
Lactate
reagents
diagnosis. Many of the enzymes are not
reagents
1.
Description.
Many
purified
enzymes
are
now commercially
ISOZYMES)
precursor
(proteolytic
cleavage)
Glucose
oxydase
Determination
of
serum
glucose forms of
MECHANISMS
FOR
REGULATING
ENZYME
specific
for
the
disease
listed
levels
Definition.
Isozymes
are
different
molecular
available
for
use
in
the
determination
of
components
in
blood
and
1.
Description.
Many
enzymes
are
Serum
Enzyme
Major
Diagnostic
tissues.
Such
enzymatic assays
are usually
more
specific, more
level
Cholesterol
oxydase
Determination
ofsame or
ACTIVITY
enzymes
that
may
be
isolated
from
the
sensitive, and in
faster
than chemical
determinations.
present
serum,
and
their
activity Resul
Aminotransferases
Use
Myocardial
Regulator
Typica
Time required
serum
cholesterol
level
Lipase
Determination
of
2.
Clinical
use.
Examples
of
clinically
relevant
compounds
that can
l
(
under
myocardial
1
proteolytic
different
tissues.
Subunits
can
be
easily
assayed
without
Aspartate
aminotransferinfarction
Viral
be
determined
en-zymatically
glucose,
ethanol,
and
for change
Most
isoenzymes
areinclude
enzymes
that
catalyze
the same
reaction
but
event
l urea,
ts
triacylglycerol
level
Urease
Determination
of
triglycerides.
ase
(AST,
SGOT)
hepatitis
differ
Substrate
in or
their
physicalenzyme
properties
becausein of
velocity
genetically
determined
effect Change
purification.
Zymogen
Active
HHHH
infarction)
2.
Clinical
use.
Elevation
or
serum
urea
level
Dehydrogenase
Alanine
aminotransferase
Change in V
differences
in amino acidor sequence.
Isoenzymes
may contain
Immediat
availability
m
enzyme
depression
of of
the
levels
ofand/or
activity
of
Acuteamino
pancreatitis
(ALT,
or SGPT)
Kmand
Change
different
numbers
charged
acids
may be separated
from
Substrate
e
Product
inhibition
lIsozyme
2
Inactive
Hepatolenticular
Amylase
in
Vm and/or
Km
specific
enzymes
may
indicate
either
each
other
by elec-trophoresis.
Different
organs
frequently
contain
Product
Immediat
Allosteric
control
enzyme
degenera-tion
Ceruloplas
Change
in Vm
characteristic
proportions
of different
e
Covalent
the
presence
of a End
disease
orisoenzymes.
damage
Creatine
(Wilson's Change
disease)
min
and/or
Kin
Dissociation/associatio
product
Immediat
modification
m Vm
to
a
specific
tissue.
HHHM
l
3use.
kinase
Muscle
n of regulatory
protein
Another
Clinical
Analysis
ofdisorders
the
ofe to
isozymes
and/ordistribution
Kand
m
-Glutamyl
myo-cardial
(modulatory
protein
enzyme
minutes
of
particular
enzymes
is
sometimes
a
useful
tool in
peptide
transpeptidase
infarctionChange in the amount Hours
binding) Synthesis or Hormone
to
Second
Immediat
clinical
Lactate
Various
liver
days
degradation
of the
enzyme
messeng
e
HHMMdiagnosis.
l4of enzyme or
dehydrogenase
metabolit
Acute pancreatitis
diseases
ers
e Metastatic
(isozymes)
carcinoma
Myocardial
Lipase
of the prostate
infarction
HMMM
l
5
Phosphatase, alkaline
Various bone
(isozymes)
disorders, obacid
structive liver
diseases
MMMM