Biomedical Engineering Reference
In-Depth Information
NADH
þ
H
þ
2
goes through a similar process but starts at coen-
zyme Q, where it directly provides a pair of electrons. Thus,
In parallel with
ð
Þ
,
FADH
2
provides two fewer
FADH
hydrogen ions than
.
The focus of this section has been the synthesis of ATP. Glycolysis and the Krebs cycle
are also important in the synthesis of small molecules such as amino acids and nucleotides,
and large molecules such as proteins, DNA, and RNA. There are other metabolic pathways
to store and release energy that were not covered here. The interested reader can learn
more about these pathways using the references at the end of this chapter and the website
http://www.genome.jp.
ð
NADH
þ
H
þ
Þ
8.6 ENZYME INHIBITION, ALLOSTERIC MODIFIERS,
AND COOPERATIVE REACTIONS
Up to this point, we have considered the case of an enzyme binding with one substrate to
make a product. Here, we examine the case in which the enzyme is free to bind with more
than one molecule and form a product. As we will see, these reactions can regulate the
amount of product synthesized and change the overall reaction rate in forming the product.
In this section, we begin with enzyme inhibitors that are either competitive or allosteric.
A competitive enzyme inhibitor, referred to as the inhibitor, binds to the active site on the
enzyme and prevents the substrate from binding with the enzyme. Thus, the inhibitor com-
petes with the substrate to bind with the substrate and reduces the synthesis of the product
and its overall reaction rate.
Some enzymes have more than one binding site and are called allosteric enzymes. The
site that binds with the substrate is called the active site. The other site, called the allosteric
or regulatory site, binds with another molecule called a modifier or effector. A modifier
binds to the regulatory site on the enzyme and doesn't directly block the binding of the sub-
strate with the enzyme at the active site. The effector role is to either increase (allosteric acti-
vator) or decrease (allosteric inhibitor) the activity of the enzyme. Some refer to allosteric
inhibition as noncompetitive inhibition.
Finally, we examine reactions that are cooperative. These reactions are sequential and
have a sigmoidal reaction velocity.
8.6.1 Competitive Enzyme Inhibitors
Consider an enzyme catalyzed reaction between a substrate,
S
, and enzyme,
E
, synthesiz-
ing product,
P
1
,as
ð
8
:
114
Þ
and another enzyme reaction, where enzyme inhibitor
I
reacts with
E
to form product
P
2
as
ð
8
:
115
Þ
where
2
are the intermediate complexes. Note that we have eliminated the reverse
reaction from the product to the intermediate complex. Another form of a competitive
enzyme inhibitor eliminates the formation of product
C
1
and
C
P
ð
i
:
e.,
K
¼
0
Þ:
2
4
