104
chapter 6
Enzymes I: General Properties, Kinetics, and Inhibition
TABLE 6-4
Proteinoses and Their Putative Extracellular Matrix Targets
Proteinases
Functions/Targets of Degradation
Serine proteinases
Urokinase plasminogen activator (uPA)
Tissue-type plasminogen activator (tPA)
Plasminogen
Plasmin
Thrombin
Elastase
Cathepsins
Cathepsin D (aspartic proteinase)
Cathepsin B, L (cysteine proteinases)
Cathepsin G (serine proteinase)
Cathepsin 02 (similar to cathepsins S and L)
Integral membrane proteinases
Matrix metalloproteinases (MMP)
MMP-1 interstitial collagenase
Neutrophil collagenase
MMP-2 (type IV collagenase, gelatinase) (two major forms)
MMP-9 (type IV collagenase)
MMP-3 (Stromelysin-1 )
MMP-10 (Stromelysin-2, transin)
MMP-11 (Stromelysin-3)
MMP-4
MMP-5
MMP
- 6
Acid metalloproteinase
MMP-7 (pump-1)
Activation of plasminogen
Activation of plasminogen
Laminin, type IV collagen
Collagens, laminin
Localized ECM degradation
Degradation of interstitial collagen types I, II, III, VII
Collagen I
Types I, II, III, IV, V, VII collagens, fibronectin
Types IV, IX collagens, laminin, fibronectin
Types III, IV, V collagens, fibronectin
a
j
-chain of type I collagen
Native 3A collagen fragments
Cartilage proteoglycan
Gelatin of types I, III, IV, V collagens, fibronectin
Reproduced with permission from
T h e G e n e tic s o f C a n cer,
G. V. Sherbet and M. S. Lakshmi. Academic Press, 1997.
6.5 Kinetics of Ligand-Receptor Interaction
The kinetics of enzyme-substrate interactions can be ap-
plied to ligand-receptor relationships. A ligand (e.g., a
hormone or a drug) can saturate the receptor sites as well
as dissociate from them, similar to enzyme-substrate in-
teractions. Nonspecific ligand binding, on the other hand,
shows a relatively low affinity to the receptor and nonsat-
uration kinetics. In ligand-receptor binding, no product
is formed, but effects responsible for the ligand’s biolog-
ical action are produced (Chapter 30). Cells that contain
a receptor protein specific for a particular hormone are
targets for the action of that hormone. The activity of a
ligand on a target cell depends on the concentration of
ligand, the binding affinity of the ligand to the recep-
tor sites, the number of receptors bound, and the dura-
tion of binding. Ligands that compete for binding to a
receptor at a specific site and produce the same biological
response are known as
agonists.
A ligand that competes
with an agonist for binding to a receptor and causes a
blockage or inhibition of the biological response of the cell
is known as an
antagonist.
Antagonists are similar to com-
petitive inhibitors of enzymes. Consider a ligand-receptor
interaction,
L + R ^ LR
(
6
.
8
)
where L is the ligand, R is the free receptor site, and LR
is the ligand bound to the receptor site. We apply the law
of mass action to the above equilibrium,
=
[LR]
[L] [R]
(6.9)
where
Kd
is the association constant. The reciprocal of
KA
represents the dissociation constant known as
K&.
Thus,
1
1
K,
= —
orX d = — .
A d
A a
