amino acid composition, their activity pH optima
lie between 7.5 and 8.5 [36]. It has already been
mentioned that the basic phospholipases A2, in
contrast to the acidic variety, are, without exception, toxic, and that during snake venom evolution they formed the origin of highly effective toxins at the expense of their enzyme activity.
Snake venoms may contain numerous proteases of varying specificity. For example, five
clotting-inhibitory (haemorrhagic) Zn 2 + proteases have been detected in the rattlesnake Crotalus, together with a non-haemorrhagic collagenase, two kallikrein-like arginine esterases, four
other clotting-inhibitory proteases, four anticomplement factors, plus two fibrinolytic and three
caseinolytic activities, i.e. a total of 21 protease
activities, several of which, however, are probably identical [6]. Zn 2 + proteases with broader
specificity are widely found in viperid and crotalid
venoms but are absent from those of the elapids
and sea snakes, which often contain oligopeptidases. Highly specific proteases, however, make an
important contribution to the effectiveness of
snake venoms. Thus, for example, clottinginhibitory or promo tory enzymes result in internal bleeding (haemorrhages) or the formation of
intravasal blood clots, and thereby amplify the
lethal effects of the snake bite. Haemorrhagic
Zn2+ -proteases are found, above all, in the venom
of the viperids and crotalids [6], but one such
enzyme is also present in the elapid Naja nigicollis. This enzyme destroys erythrocytes and punctures capillary walls by hydrolysing collagen IV
and other protein components of the endothelium basal membrane [65].
In addition to haemorrhagic metalloenzymes,
venom secretions may at the same time contain
thrombin-like serine proteases. These enzymes,
however, attack only the Aa chain or, less often,
the B~ chain of fibrinogen and in no case form
insoluble fibrin [17, 28]. The best-known of these
enzymes, batroxobin from Bothrops atrox, shows
only 31 % sequence agreement with human
thrombin and can only cleave the Aa chain of fibrinogen. The batroxobin gene is much more similar in its exonlintron organization to the genes of
the kallikreins and trypsins than to the thrombin
gene. Thus, batroxobin apparently originates
from glandular kallikreins [28]. There are further
venom components which influence blood clotting. The echistatin of the viper Echis carinatus
(49 amino acids) or arietin from Bitis arietans are
antagonists of the fibrinogen receptor and inhibit
clotting by preventing platelet aggregation [25].
The venom of the southern copperhead snake
9.1.2 Enzymes and Other Protein Components
323
Agkistrodon contortrix contains a serine protease
which activates plasma protein C; this in turn
hydrolyses the factors Va and VIlla and thereby
inhibits clotting [44]. The serine protease cerastobin from the horned viper Cerastes cerastes activates factor X, and thus promotes clotting [17].
A large proportion of the activity of venom
secretions is due to kinins and kinin-releasing
enzymes. The peptide bradykinin, and its effect
of reducing the blood pressure, was in fact first
discovered in 1949 in investigations of the action
of the venom from Bothrops jararaca on mammalian blood plasma. All viperid and crotalid
venoms contain enzymes which release bradykinin or kallidin from the precursor kininogen in
mammalian plasma (see Fig.8.5, p.302). Such
kininogenases are similar to the mammalian kallikrein, are unusually heat resistant, and can be
separated from the arginine esterases and
thrombin-like enzymes [36, 50]. The biological
significance of other enzymes and protein components of the snake venoms is not completely
clear. Acetylcholine esterases are widely found in
the venoms of the elapids and hydrophiids but
not in those of the viperids and crotalids [36]. The
L-amino acid oxidases of snake venoms differ
from the corresponding enzymes of mammalian
tissues in their coenzyme (FAD instead of FMN)
and in the more than 100-fold higher activity.
These enzymes are found at significantly higher
concentration in the viperids and crotalids than in
the elapids and impart the yellow colour to the
venom. White venom without the FAD enzyme is
found in the hydrophiids and several species of
the viperids and crotalids. The enzymes of the different species appear to be very similar in their
catalytic and physicochemical properties [36, 71].
Protease inhibitors have been isolated from
various snake venoms and in some cases have
been sequenced; they apparently all belong to the
pancreas-trypsin inhibitor (Kunitz) family but are
in part specific for chymotrypsin [53]. Amongst
the most surprising components of snake venoms
are the nerve growth factors (NGFs). These are
present at low concentrations in many vertebrate
tissues, but occur at high concentration only in
the submaxillary glands of several mouse species
and in the venom glands of most poisonous snakes. NGFs promote the growth and differentiation of neurons, particularly those of the sympathetic nervous system; their role in snake venoms
is something of a mystery. Venom secretions contain only the bioactive ~ chain; they lack the a
and y chains found in the high molecular weight
NGF complexes of mammalian tissues. The
lie between 7.5 and 8.5 [36]. It has already been
mentioned that the basic phospholipases A2, in
contrast to the acidic variety, are, without exception, toxic, and that during snake venom evolution they formed the origin of highly effective toxins at the expense of their enzyme activity.
Snake venoms may contain numerous proteases of varying specificity. For example, five
clotting-inhibitory (haemorrhagic) Zn 2 + proteases have been detected in the rattlesnake Crotalus, together with a non-haemorrhagic collagenase, two kallikrein-like arginine esterases, four
other clotting-inhibitory proteases, four anticomplement factors, plus two fibrinolytic and three
caseinolytic activities, i.e. a total of 21 protease
activities, several of which, however, are probably identical [6]. Zn 2 + proteases with broader
specificity are widely found in viperid and crotalid
venoms but are absent from those of the elapids
and sea snakes, which often contain oligopeptidases. Highly specific proteases, however, make an
important contribution to the effectiveness of
snake venoms. Thus, for example, clottinginhibitory or promo tory enzymes result in internal bleeding (haemorrhages) or the formation of
intravasal blood clots, and thereby amplify the
lethal effects of the snake bite. Haemorrhagic
Zn2+ -proteases are found, above all, in the venom
of the viperids and crotalids [6], but one such
enzyme is also present in the elapid Naja nigicollis. This enzyme destroys erythrocytes and punctures capillary walls by hydrolysing collagen IV
and other protein components of the endothelium basal membrane [65].
In addition to haemorrhagic metalloenzymes,
venom secretions may at the same time contain
thrombin-like serine proteases. These enzymes,
however, attack only the Aa chain or, less often,
the B~ chain of fibrinogen and in no case form
insoluble fibrin [17, 28]. The best-known of these
enzymes, batroxobin from Bothrops atrox, shows
only 31 % sequence agreement with human
thrombin and can only cleave the Aa chain of fibrinogen. The batroxobin gene is much more similar in its exonlintron organization to the genes of
the kallikreins and trypsins than to the thrombin
gene. Thus, batroxobin apparently originates
from glandular kallikreins [28]. There are further
venom components which influence blood clotting. The echistatin of the viper Echis carinatus
(49 amino acids) or arietin from Bitis arietans are
antagonists of the fibrinogen receptor and inhibit
clotting by preventing platelet aggregation [25].
The venom of the southern copperhead snake
9.1.2 Enzymes and Other Protein Components
323
Agkistrodon contortrix contains a serine protease
which activates plasma protein C; this in turn
hydrolyses the factors Va and VIlla and thereby
inhibits clotting [44]. The serine protease cerastobin from the horned viper Cerastes cerastes activates factor X, and thus promotes clotting [17].
A large proportion of the activity of venom
secretions is due to kinins and kinin-releasing
enzymes. The peptide bradykinin, and its effect
of reducing the blood pressure, was in fact first
discovered in 1949 in investigations of the action
of the venom from Bothrops jararaca on mammalian blood plasma. All viperid and crotalid
venoms contain enzymes which release bradykinin or kallidin from the precursor kininogen in
mammalian plasma (see Fig.8.5, p.302). Such
kininogenases are similar to the mammalian kallikrein, are unusually heat resistant, and can be
separated from the arginine esterases and
thrombin-like enzymes [36, 50]. The biological
significance of other enzymes and protein components of the snake venoms is not completely
clear. Acetylcholine esterases are widely found in
the venoms of the elapids and hydrophiids but
not in those of the viperids and crotalids [36]. The
L-amino acid oxidases of snake venoms differ
from the corresponding enzymes of mammalian
tissues in their coenzyme (FAD instead of FMN)
and in the more than 100-fold higher activity.
These enzymes are found at significantly higher
concentration in the viperids and crotalids than in
the elapids and impart the yellow colour to the
venom. White venom without the FAD enzyme is
found in the hydrophiids and several species of
the viperids and crotalids. The enzymes of the different species appear to be very similar in their
catalytic and physicochemical properties [36, 71].
Protease inhibitors have been isolated from
various snake venoms and in some cases have
been sequenced; they apparently all belong to the
pancreas-trypsin inhibitor (Kunitz) family but are
in part specific for chymotrypsin [53]. Amongst
the most surprising components of snake venoms
are the nerve growth factors (NGFs). These are
present at low concentrations in many vertebrate
tissues, but occur at high concentration only in
the submaxillary glands of several mouse species
and in the venom glands of most poisonous snakes. NGFs promote the growth and differentiation of neurons, particularly those of the sympathetic nervous system; their role in snake venoms
is something of a mystery. Venom secretions contain only the bioactive ~ chain; they lack the a
and y chains found in the high molecular weight
NGF complexes of mammalian tissues. The