Part D | 22.5
568 Part D Marine Algal Biotechnology
tivation. A different mechanism predominates over the
conformational activation of antithrombin in ensuring
the antithrombin-mediated anticoagulant activity of the
sulfated galactans. Possibly, sulfated galactan connects
antithrombin and thrombin, holding the protease in an
inactive form. The conformational activation of antithrombin and the consequent formation of a covalent
complex with thrombin appear to be less important for
the anticoagulant activity of sulfated galactan than for
heparin [22.338]. The (1 ! 3)-˛-L-galactan, but not
˛-L-fucan, sulfated at O-2 is a potent thrombin inhibitor mediated by antithrombin or heparin cofactor
II; these two polysaccharides show similar inhibitions
when factor Xa is used instead of thrombin [22.423].
The proportion and/or distribution of 2,3-disulfated
˛-Galp units along the galactan chain may be a critical structural motif to promote the interaction of the
protease with specific protease and coagulation inhibitors [22.338, 424]. In contrast to the linear fucans
from echinoderms and mammalian glycosaminoglycans, which need thrombin inhibitors (antithrombin or
heparin cofactor II) for a reasonable anticoagulant effect, branched fucans (fucoidans) from brown algae
are direct inhibitors of thrombin [22.425]. The occurrence of 2,4-di-O-sulfated units is an amplifying motif
for 3-linked ˛-fucan-enhanced thrombin inhibition by
antithrombin. If we replace antithrombin by heparin
cofactor II, then the major structural requirement for
the activity becomes single 4-O-sulfated fucose units,
while the presence of 2-O-sulfated fucose residues
always inhibits anticoagulant activity [22.424]. Therefore, the anticoagulant activities of sulfated galactans
and fucans are not determined only by their charge
density. The structural requirements for interaction of
sulfated galactans and sulfated fucans with coagulation
cofactors and their target proteases are stereospecific
and not merely a consequence of their charge density and sulfate content [22.423, 424]. The unusual
sulfated D-galactan (hybrid carrageenan) from Botryocladia occidentalis demonstrate marked anticoagulant
activity via enhanced inhibition of thrombin and factor
Xa by antithrombin and/or heparin cofactor II [22.62].
Disulfated ˛-Galp units seem to be necessary for effective anticoagulant action, while high negative charge
density itself is not so important. Sulfated galactofucan from Spatoglossum schroederi does not show
any in vitro anticoagulant activity but demonstrates
a potent antithrombotic activity in vivo and strong
stimulation of the synthesis of heparan sulfate by endothelial cells. These effects have not bee observed after
desulfation [22.142].
22.5.6 Antioxidant Activities
Because they are important for living organisms, enzymatic or nonenzymatic oxidative reactions can be
destructive in some cases. Many products, including
reactive oxygen species (ROS) and other free radicals are commonly produced by the oxidation of lipids
and other biomolecules. These products promote chain
reactions that cause the destruction of cellular structures and hence cell death. Antioxidants, in turn, may
terminate chain reactions by free radical scavenging.
Living organisms, including marine algae, have developed regulator systems based on natural antioxidants,
both enzymatic (peroxidases, superoxide dismutase,
and catalase) and nonenzymatic (glutathione, vitamins
A, C, and E). If such systems do not work well, oxidative stress may occur and lead to various pathological
states. Therefore, antioxidants might prevent many diseases, including degenerative ones, and thus promote
human health and longevity. Algal antioxidants including sulfated polysaccharides have been reviewed in the
context of algal biology and utilization [22.426]. The
antioxidant activity of algal polysaccharides is defined
as their ability to inhibit model oxidation processes;
some examples are given in Table 22.12. The antioxidant properties of algal polysaccharides and associated
compounds are commonly established as (i) DPPH
(2,2-diphenyl-1-picrylhydrazyl) free-radical scavenging, (ii) oxygen radical absorbance capacity (ORAC),
(iii) ferric ion reducing antioxidant power (FRAP) or
ferrous ion chelating ability (FCA), (iv) ABTS (2,2
0 -
azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), and
(v) ROS scavenging assays [22.427]. Structure and
sulfation patterns may influence these antioxidant effects of algal polysaccharides. It has been reported
that Ã-carrageenan demonstrates higher hydroxyl radical scavenging than and Ä-carrageenans [22.328].
Alternatively, algal polysaccharides have been tested in
accordance with in vitro and in vivo responses to experimental oxidative stress. For example, it has been
reported that ulvan-like sulfated polysaccharide from
Ulva lactuca stabilizes mitochondrial and microsomal
membranes by prevention of the oxidative stress induced by D-GalN [22.319].
22.5.7 Medicinal Materials
Based on Algal Polysaccharides
Algal cell wall polysaccharides have great potential
for medicinal applications because of their biocompatibility with human tissues, their biodegradability, and
568 Part D Marine Algal Biotechnology
tivation. A different mechanism predominates over the
conformational activation of antithrombin in ensuring
the antithrombin-mediated anticoagulant activity of the
sulfated galactans. Possibly, sulfated galactan connects
antithrombin and thrombin, holding the protease in an
inactive form. The conformational activation of antithrombin and the consequent formation of a covalent
complex with thrombin appear to be less important for
the anticoagulant activity of sulfated galactan than for
heparin [22.338]. The (1 ! 3)-˛-L-galactan, but not
˛-L-fucan, sulfated at O-2 is a potent thrombin inhibitor mediated by antithrombin or heparin cofactor
II; these two polysaccharides show similar inhibitions
when factor Xa is used instead of thrombin [22.423].
The proportion and/or distribution of 2,3-disulfated
˛-Galp units along the galactan chain may be a critical structural motif to promote the interaction of the
protease with specific protease and coagulation inhibitors [22.338, 424]. In contrast to the linear fucans
from echinoderms and mammalian glycosaminoglycans, which need thrombin inhibitors (antithrombin or
heparin cofactor II) for a reasonable anticoagulant effect, branched fucans (fucoidans) from brown algae
are direct inhibitors of thrombin [22.425]. The occurrence of 2,4-di-O-sulfated units is an amplifying motif
for 3-linked ˛-fucan-enhanced thrombin inhibition by
antithrombin. If we replace antithrombin by heparin
cofactor II, then the major structural requirement for
the activity becomes single 4-O-sulfated fucose units,
while the presence of 2-O-sulfated fucose residues
always inhibits anticoagulant activity [22.424]. Therefore, the anticoagulant activities of sulfated galactans
and fucans are not determined only by their charge
density. The structural requirements for interaction of
sulfated galactans and sulfated fucans with coagulation
cofactors and their target proteases are stereospecific
and not merely a consequence of their charge density and sulfate content [22.423, 424]. The unusual
sulfated D-galactan (hybrid carrageenan) from Botryocladia occidentalis demonstrate marked anticoagulant
activity via enhanced inhibition of thrombin and factor
Xa by antithrombin and/or heparin cofactor II [22.62].
Disulfated ˛-Galp units seem to be necessary for effective anticoagulant action, while high negative charge
density itself is not so important. Sulfated galactofucan from Spatoglossum schroederi does not show
any in vitro anticoagulant activity but demonstrates
a potent antithrombotic activity in vivo and strong
stimulation of the synthesis of heparan sulfate by endothelial cells. These effects have not bee observed after
desulfation [22.142].
22.5.6 Antioxidant Activities
Because they are important for living organisms, enzymatic or nonenzymatic oxidative reactions can be
destructive in some cases. Many products, including
reactive oxygen species (ROS) and other free radicals are commonly produced by the oxidation of lipids
and other biomolecules. These products promote chain
reactions that cause the destruction of cellular structures and hence cell death. Antioxidants, in turn, may
terminate chain reactions by free radical scavenging.
Living organisms, including marine algae, have developed regulator systems based on natural antioxidants,
both enzymatic (peroxidases, superoxide dismutase,
and catalase) and nonenzymatic (glutathione, vitamins
A, C, and E). If such systems do not work well, oxidative stress may occur and lead to various pathological
states. Therefore, antioxidants might prevent many diseases, including degenerative ones, and thus promote
human health and longevity. Algal antioxidants including sulfated polysaccharides have been reviewed in the
context of algal biology and utilization [22.426]. The
antioxidant activity of algal polysaccharides is defined
as their ability to inhibit model oxidation processes;
some examples are given in Table 22.12. The antioxidant properties of algal polysaccharides and associated
compounds are commonly established as (i) DPPH
(2,2-diphenyl-1-picrylhydrazyl) free-radical scavenging, (ii) oxygen radical absorbance capacity (ORAC),
(iii) ferric ion reducing antioxidant power (FRAP) or
ferrous ion chelating ability (FCA), (iv) ABTS (2,2
0 -
azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), and
(v) ROS scavenging assays [22.427]. Structure and
sulfation patterns may influence these antioxidant effects of algal polysaccharides. It has been reported
that Ã-carrageenan demonstrates higher hydroxyl radical scavenging than and Ä-carrageenans [22.328].
Alternatively, algal polysaccharides have been tested in
accordance with in vitro and in vivo responses to experimental oxidative stress. For example, it has been
reported that ulvan-like sulfated polysaccharide from
Ulva lactuca stabilizes mitochondrial and microsomal
membranes by prevention of the oxidative stress induced by D-GalN [22.319].
22.5.7 Medicinal Materials
Based on Algal Polysaccharides
Algal cell wall polysaccharides have great potential
for medicinal applications because of their biocompatibility with human tissues, their biodegradability, and