190
5 Plasma Proteins, Yolk Proteins and Metal-Binding Proteins
meric protein with 11-12 disulphide bridges in the
chain. It binds haemoglobin from bird and reptile
blood but not from human blood; conversely,
however, mammalian haptoglobin binds chicken
haemoglobin [60]
The haemopexins are ~-glycoproteins that bind
free haem and transport it to the liver cells, where
it is degraded to gall pigments and the iron is
bound to ferritin; the haemopexin returns to the
bloodstream. Human haemopexin has a native
molecular mass of about 600 kDa with 20 % carbohydrate; the polypeptide chain of 439 amino
acids contains at least eight repeats of ca. 45
amino acids [4]. Haemopexin appears to exist in
all classes of vertebrates and apparently has a
relatively low rate of evolution. Antisera against
human haemopexin react with the haemopexins
of all placental mammals but not with those of the
marsupials or other vertebrate classes. As in the
case of haptoglobin, chicken haemopexin differs
markedly from that of man and the mammals: it
migrates in the al instead of the ~ fraction during
electrophoresis and contains different carbohydrate components [194].
5.3.3 Caeruloplasmin and Pre-Albumins
Human caeruloplasmin is a blue az-glycoprotein
of 132 kDa which carries over 90 % of the copper
transported iIi the blood plasma. There are six or
eight copper-binding sites with a high affinity and
a further ten with a lower affinity. In addition, the
caeruloplasmin molecule has the enzyme activities of a ferroxidase, aminoxidase and superoxide
dismutase. It is synthesized in the liver and
increases in concentration as an acute-phase protein in response to inflammation. The polypeptide chain of human caeruloplasmin consists of
1046 amino acids and is subdivided into three
domains. There is 93 % agreement with the protein from the rat. A similar domain structure is
found in the clotting factors V and VIII, which
belong to the same protein super-family [75, 133].
Caeruloplasmins appear to be generally distributed throughout the vertebrates and are also
identifiable in the cartilaginous fish on the basis
of their copper content and aminoxidase activity
[25,34, 105].
'fiansthyretin or pre-albumin, which runs in
front of albumin on electrophoregrams of vertebrate plasma, has been identified in man and
other mammals as a protein with a double transport function: it binds thyroxin and also the
retinol-binding protein. The protein is a homotetramer with 14-kDa subunits of 127 amino acids
that form a central canal containing the thyroxinbinding site. The amino acid sequences from
man, sheep, rabbit, rat and mouse have been
determined either directly or via cDNA; they
show 80 % agreement and also have significant
homology to human thyroxin-binding-protein, a
further, functionally more important transport
protein for the thyroid hormone [114,246, 260].
Transthyretin is made in adult and foetal livers
and in the yolk-sac of early embryos. Large
amounts of transthyretin mRNA are also found in
the chorioid plexus on the inner surface of the
neural canal; thus, transthyretin is apparently
important for the transport of the thyroid hormone from the blood to the brain and the spinal
cord. Transthyretin made in the retina is possibly
involved in the transport of retinal [81, 158].
5.4 Acute-Phase Proteins
One response to bacterial infection or certain
irritants by man and many mammals is a drastic
increase in the concentration of several plasma
proteins (acute-phase reaction). In the human
acute phase, 100- to 1000-fold increases in concentration occur for the C-reactive protein (CRP)
and the serum amyloid protein (SAP), and fourto ten-fold increases, for example, in the case of
the acid arglycoprotein or orosomucoid, alantitrypsin, az-macroglobulin, haptoglobin, haemopexin, fibrinogen and several complement factors. An acute-phase reaction is also observed in
many mammals but both the spectrum of proteins
and the increases in their concentration vary with
the species [50]. The most important regulator of
the acute-phase reaction is interleukin-6.
The C-reactive protein (CRP) gets its name
from its ability to precipitate the C-polysaccharide of Streptococcus pneumoniae in the
presence of Ca 2 +. It has a very unusual molecular
structure in which five identical subunits of 22.5
kDa are associated non-covalently into diskshaped pentamers. The evolution of CRP is relatively slow; the 205 amino acids of the mouse and
rabbit CRPs agree 70-80 % with human CRP
[270]. A CRP induced by pathogenic bacteria has
also been found in the trout Salmo gairdneri
[178]. The protein super-family (pentraxine), of
which CRP is a member, also includes the serum
amyloid protein (SAP), which is constructed of
two pentameric disks, and the SAP-related,
female-specific protein (hamster female protein,
5 Plasma Proteins, Yolk Proteins and Metal-Binding Proteins
meric protein with 11-12 disulphide bridges in the
chain. It binds haemoglobin from bird and reptile
blood but not from human blood; conversely,
however, mammalian haptoglobin binds chicken
haemoglobin [60]
The haemopexins are ~-glycoproteins that bind
free haem and transport it to the liver cells, where
it is degraded to gall pigments and the iron is
bound to ferritin; the haemopexin returns to the
bloodstream. Human haemopexin has a native
molecular mass of about 600 kDa with 20 % carbohydrate; the polypeptide chain of 439 amino
acids contains at least eight repeats of ca. 45
amino acids [4]. Haemopexin appears to exist in
all classes of vertebrates and apparently has a
relatively low rate of evolution. Antisera against
human haemopexin react with the haemopexins
of all placental mammals but not with those of the
marsupials or other vertebrate classes. As in the
case of haptoglobin, chicken haemopexin differs
markedly from that of man and the mammals: it
migrates in the al instead of the ~ fraction during
electrophoresis and contains different carbohydrate components [194].
5.3.3 Caeruloplasmin and Pre-Albumins
Human caeruloplasmin is a blue az-glycoprotein
of 132 kDa which carries over 90 % of the copper
transported iIi the blood plasma. There are six or
eight copper-binding sites with a high affinity and
a further ten with a lower affinity. In addition, the
caeruloplasmin molecule has the enzyme activities of a ferroxidase, aminoxidase and superoxide
dismutase. It is synthesized in the liver and
increases in concentration as an acute-phase protein in response to inflammation. The polypeptide chain of human caeruloplasmin consists of
1046 amino acids and is subdivided into three
domains. There is 93 % agreement with the protein from the rat. A similar domain structure is
found in the clotting factors V and VIII, which
belong to the same protein super-family [75, 133].
Caeruloplasmins appear to be generally distributed throughout the vertebrates and are also
identifiable in the cartilaginous fish on the basis
of their copper content and aminoxidase activity
[25,34, 105].
'fiansthyretin or pre-albumin, which runs in
front of albumin on electrophoregrams of vertebrate plasma, has been identified in man and
other mammals as a protein with a double transport function: it binds thyroxin and also the
retinol-binding protein. The protein is a homotetramer with 14-kDa subunits of 127 amino acids
that form a central canal containing the thyroxinbinding site. The amino acid sequences from
man, sheep, rabbit, rat and mouse have been
determined either directly or via cDNA; they
show 80 % agreement and also have significant
homology to human thyroxin-binding-protein, a
further, functionally more important transport
protein for the thyroid hormone [114,246, 260].
Transthyretin is made in adult and foetal livers
and in the yolk-sac of early embryos. Large
amounts of transthyretin mRNA are also found in
the chorioid plexus on the inner surface of the
neural canal; thus, transthyretin is apparently
important for the transport of the thyroid hormone from the blood to the brain and the spinal
cord. Transthyretin made in the retina is possibly
involved in the transport of retinal [81, 158].
5.4 Acute-Phase Proteins
One response to bacterial infection or certain
irritants by man and many mammals is a drastic
increase in the concentration of several plasma
proteins (acute-phase reaction). In the human
acute phase, 100- to 1000-fold increases in concentration occur for the C-reactive protein (CRP)
and the serum amyloid protein (SAP), and fourto ten-fold increases, for example, in the case of
the acid arglycoprotein or orosomucoid, alantitrypsin, az-macroglobulin, haptoglobin, haemopexin, fibrinogen and several complement factors. An acute-phase reaction is also observed in
many mammals but both the spectrum of proteins
and the increases in their concentration vary with
the species [50]. The most important regulator of
the acute-phase reaction is interleukin-6.
The C-reactive protein (CRP) gets its name
from its ability to precipitate the C-polysaccharide of Streptococcus pneumoniae in the
presence of Ca 2 +. It has a very unusual molecular
structure in which five identical subunits of 22.5
kDa are associated non-covalently into diskshaped pentamers. The evolution of CRP is relatively slow; the 205 amino acids of the mouse and
rabbit CRPs agree 70-80 % with human CRP
[270]. A CRP induced by pathogenic bacteria has
also been found in the trout Salmo gairdneri
[178]. The protein super-family (pentraxine), of
which CRP is a member, also includes the serum
amyloid protein (SAP), which is constructed of
two pentameric disks, and the SAP-related,
female-specific protein (hamster female protein,