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Regulation
of
Enzyme
Activity |
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Regulation
of
Enzyme
Activity -
As
described
other
topics,
the
catalytic
activity
of
many
proteins
is
affected
by
their
binding
to
specific
small
molecules.
In
this
way,
the
activity
of
enzymes
can
be
reduced
when
they
are
not
required.
Several
enzymes
are
known
whose
activity
can
be
inhibited
by
end
products
and
classical
examples
arc
aspartokinase,
and
aspartate
transcarbamylase
which
are
the
first
enzymes
in
the
purine
or
pyrimidine
biosynthetic
pathways.
In
these,
the
final
step
in
the
synthesis
of
an
end
product
is
separated
by
several
intermediate
metabolic
steps.
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This
specific
inhibition
by
the
end
product
is
called
feed
back
of
end
product
inhibition.
The
exact
mechanism
of
inhibition
involves
the
binding
of
the
end
product
to
the
enzyme,
causing
a
structural
change
(allosteric
transformation)
and
preventing
the
enzyme
from
binding
to
the
substrate.
Many
biosynthetic
pathways
have
two
or
more
end
products.
Feedback
inhibition
in
such
pathways
,is
much
more
complex
than
in
un
branched
pathways. In
a
branched
pathway
leading
to
the
synthesis
of
more
than
one
product,
complete
feedback
inhibition
by
anyone
of
the
end
products
will
lead
to
cessation
of
growth.
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To
avoid
this,
microorganisms
have
evolved
a
mechanism
by
which
feedback
inhibition,
by
the
end
product
of
a
branched
biosynthetic
pathway,
is
exerted
specifically
on
the
enzyme
that
catalyses
the
initial
step
following
the
branch
point
thus
allowing
synthesis
of
the
other
end
products
Today,
fit
least
five
different
types
of
feedback
mechanisms
are known
to
exist:
(i)
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When
the
cell
synthesises
two
enzymes
(isozymes)
that
catalyse
the
first
reaction,
the
extent
of
feedback
inhibition
by
the
end
products
will
vary.When
neither
the
end
product
is
present
the
combined
activity
of
two
enzymes
is
adequate
to
produce
sufficient
quantities
of
the
intermediates
to
meet
the
cellular
demands
for
the
synthesis
of
both
the
end
products.
When
both
the
end
products
are
present,
the
two
isozymes
are
inhibited
and
the
pathway
ceases
to
function
(ii)
In,
case
the
synthesis
of
two
end
products
is
catalysed
by
one
enzyme,
it
has
been
found
that
such
an
enzyme
possesses
two
allosteric
sites
each
of
which
can
be
bound
by
one
of
the
specific
end
products.
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Complete
inactivation
of
enzyme
occurs
only
when
both
the
effectors
(end
products)
are
bound
to
the
enzyme
and
enzyme
activity
is
not
affected
by
the
binding
of
only
one
effector.
This
type
of
control
is
termed
as
concerted
feedback
inhibition
and
prevents
the
operation
of
the
pathway
only
when
both
the
end
products
are
present
(iii)
The
third
mechanism
of
feedback
inhibition
is
the
sequential
feedback.
In
this,
the
enzyme
subject
to
inhibition
is
not
inhibited
by
the
end
product
of
the
pathway
but
an
intermediate
immediately
preceding
the
branch
point.
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A high concentration of the product inhibits the enzymes succeeding the branch point and leads to the accumulation of the intermediates before this point. An increased concentration of the intermediates in turn inhibits the activity of the first enzyme
(iv) In certain branched pathways, the first enzyme is an allosteric enzyme with different effector sites for the end products. Each end product therefore causes only a partial inhibition of the enzyme and the inhibitory effect is additive. Such control is known as cumulative feedback inhibition. These types of regulatory controls have been well demonstrated in the biosynthesis of amino acids in bacteria
(v) A fifth mechanism which is different from those described above is where a biosynthetic intermediate enters two independent pathways, one product serves as an activator while the other as an inhibitor. For example, carbamylphosphate synthetase is allosterically inhibited by UMP, an intermediate of the pyrimidine pathway, while it is activated by ornithine which is an intermediate of the arginine pathway. In the presence of excess pyrimidines the concentration of UMP increases leading to the inhibition of carbamylphosphate synthetase. The resulting decrease in carbamylphosphate concentration allows ornithine to accumulate which in turn activates carbamylphosphate synthetase so that sufficient carbamylphosphate is available for the synthesis of the alternate end product namely arginine. If arginine is available in the medium, the biosynthesis of ornithine is prevented.
Thus, a variety of mechanisms that regulate synthesis by feedback inhibition are known and all regulatory mechanisms are mediated through allosteric proteins, whose activity is altered by the binding of small molecules. With a few exceptions, the biosynthetic pathways in all microorganisms are similar; however, a given pathway in different organisms may be subject to different modes of regulation. Secondly, the synthesis of an enzyme may be both repressed as well as inhibited by the end product.
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