subunit have been isolated; type H (182 amino
acids, 21.1 kDa) predominates in the heart, and
type L (175 amino acids, 19.8 kDa) predominates in the spleen and the liver. The two polypeptide chains differ at 45 % of their positions. The
human genome contains 8L and 12H genes,
amongst which, however, there are many pseudogenes. On the basis of these findings, the heterogeneity of mammalian ferritins was initially
thought to be due to the presence in each organ
of a population of hybrid molecules which vary in
their average molecular mass according to the
proportions of two different-sized subunits: e.g.
in horse spleen 460 kDa with 10 % H, in liver
480 kDa with 40 % H, and in the heart 515 kDa
with 85 %H. It was subsequently shown that the
heterogeneity of the ferritin subunits is greater
than that expected from the HIL hypothesis.
Thus, in porcine spleen there are two different
H chains, and in the tadpole of Rana catesbeiana
there is, in addition to the H chain (175 amino
acids) and L chains, a further chain which differs
from H in 16 % of its 175 amino acids [51, 177].
SDS electrophoresis clearly shows that the subunit related to the human L chain does not always
have a molecular mass lower than that of the Hlike subunit [253].
The only ferritin genes so far characterized in
any detail are those of man and the rat; they contain three introns in the coding sequence. The H
and L mRNAs in the cytosol associate only with
polyribosomes and become active in translation
when the iron level in the cytoplasm rises; this
regulation may be the function of an upstream 28bp sequence, conserved in both man and the rat,
which can fold back on itself [179]. The ferritins
show a markedly slow evolution: the human and
rat H chains have 95 % identical amino acids and
the L chains 85 % ; the H chains of the mouse and
chicken are 89 % identical. The H chain of frog
larvae is 67 % similar to the human H chain,
compared with 61 % similarity to its own L chain
[177, 253]. Thus, the gene duplications leading to
the separation of the different chain types
occurred early in vertebrate evolution.
The iron nuclei of ferritins have diameters of
7 -8 mm and are only visible in the electron
microscope. In contrast, the iron concrescence of
a haemosiderin is visible in the light microscope,
but only with electron microscopy is it revealed as
bunches of particles which are, in fact, very similar to ferritin nuclei. These particle groups are the
residue of iron-laden secondary lysosomes (siderosomes) which have the same X-ray pattern as
ferritin and immunological similarity to ferritin
References
211
amongst their few proteins. Haemosiderins are
apparently formed from ferritins through destruction of the protein shell by lysosomal enzymes [6].
The ferritins of invertebrates appear in all
cases to be very similar to those of the mammals,
but only in a few cases have they been investigated in detail. Ferritin-like particles from many
insects have been viewed in the electron microscope but only the iron-binding haemolymph proteins of the lepidopterans have been characterized. Manduca sexta contains a 490-kDa protein
consisting of 24- and 26-kDa subunits, and in Calpodes ethlius there is a glycoprotein of 600 kDa
with 24- and 31-kDa subunits [111, 193]. The ferritins of molluscs have been investigated frequently, e.g. those involved in haemoglobin biosynthesis, or identified as components of radula
teeth, or yolk proteins in snail eggs [164]. The
apoferritin of the chiton (Polyplacophora) Clavarizona hirtosa has a molecular mass of 530 kDa,
that of the mussel Corbicula sandai 503 kDa, and
that of the earthworm Octolasium complanatum
460 kDa. Two different types of subunit have
been found in many, if not all, invertebrates, e.g.
in Clavarizona (28 and 25.5 kDa), in Octolasium
(20 and 19.7 kDa), and in the egg yolk ofthe snail
Lymnaea stagnalis (24 and 19 kDa); however,
comparison to the Hand L types of the mammals
is not reliable without sequence data [7, 131]. Of
the invertebrate ferritins mentioned above, only
that of L. stagnalis shows immunological crossreactivity to the ferritin of equine spleen [131].
Ferritin has been detected in the eggs and the
hepato-pancreas of various gastropods; this suggests that, like a typical yolk protein, ferritin is
produced in the hepato-pancreas and transported
in the blood to the oocytes. However, the subunits of egg ferritin in L. stagnalis are 24 kDa,
whereas those in the hepato-pancreas are 19 kDa
and have a different (cyanogen bromide) cleavage
peptide pattern; therefore, at least in this snail
species, the metabolic relationship between the
ferritins of the two organs is not at all clear [28].
References
1. Aketagawa J. et al.: Primary structure of Limulus
anticoagulant anti-lipopolysaccharide factor. J. biol.
Chern. 261: 7357-65 (1986)
2. Albers J. J. and SegrestJ. P. (eds.): Plasma lipoproteins. Acad. Press, New York 1986
3. Allen W. V. and Conley H.: Transport of lipids in the
blood of the Pacific oyster, Crassostrea gigas (Thunberg): Compo Biochem. Physiol. Pt. B 71: 201-207
(1982)
acids, 21.1 kDa) predominates in the heart, and
type L (175 amino acids, 19.8 kDa) predominates in the spleen and the liver. The two polypeptide chains differ at 45 % of their positions. The
human genome contains 8L and 12H genes,
amongst which, however, there are many pseudogenes. On the basis of these findings, the heterogeneity of mammalian ferritins was initially
thought to be due to the presence in each organ
of a population of hybrid molecules which vary in
their average molecular mass according to the
proportions of two different-sized subunits: e.g.
in horse spleen 460 kDa with 10 % H, in liver
480 kDa with 40 % H, and in the heart 515 kDa
with 85 %H. It was subsequently shown that the
heterogeneity of the ferritin subunits is greater
than that expected from the HIL hypothesis.
Thus, in porcine spleen there are two different
H chains, and in the tadpole of Rana catesbeiana
there is, in addition to the H chain (175 amino
acids) and L chains, a further chain which differs
from H in 16 % of its 175 amino acids [51, 177].
SDS electrophoresis clearly shows that the subunit related to the human L chain does not always
have a molecular mass lower than that of the Hlike subunit [253].
The only ferritin genes so far characterized in
any detail are those of man and the rat; they contain three introns in the coding sequence. The H
and L mRNAs in the cytosol associate only with
polyribosomes and become active in translation
when the iron level in the cytoplasm rises; this
regulation may be the function of an upstream 28bp sequence, conserved in both man and the rat,
which can fold back on itself [179]. The ferritins
show a markedly slow evolution: the human and
rat H chains have 95 % identical amino acids and
the L chains 85 % ; the H chains of the mouse and
chicken are 89 % identical. The H chain of frog
larvae is 67 % similar to the human H chain,
compared with 61 % similarity to its own L chain
[177, 253]. Thus, the gene duplications leading to
the separation of the different chain types
occurred early in vertebrate evolution.
The iron nuclei of ferritins have diameters of
7 -8 mm and are only visible in the electron
microscope. In contrast, the iron concrescence of
a haemosiderin is visible in the light microscope,
but only with electron microscopy is it revealed as
bunches of particles which are, in fact, very similar to ferritin nuclei. These particle groups are the
residue of iron-laden secondary lysosomes (siderosomes) which have the same X-ray pattern as
ferritin and immunological similarity to ferritin
References
211
amongst their few proteins. Haemosiderins are
apparently formed from ferritins through destruction of the protein shell by lysosomal enzymes [6].
The ferritins of invertebrates appear in all
cases to be very similar to those of the mammals,
but only in a few cases have they been investigated in detail. Ferritin-like particles from many
insects have been viewed in the electron microscope but only the iron-binding haemolymph proteins of the lepidopterans have been characterized. Manduca sexta contains a 490-kDa protein
consisting of 24- and 26-kDa subunits, and in Calpodes ethlius there is a glycoprotein of 600 kDa
with 24- and 31-kDa subunits [111, 193]. The ferritins of molluscs have been investigated frequently, e.g. those involved in haemoglobin biosynthesis, or identified as components of radula
teeth, or yolk proteins in snail eggs [164]. The
apoferritin of the chiton (Polyplacophora) Clavarizona hirtosa has a molecular mass of 530 kDa,
that of the mussel Corbicula sandai 503 kDa, and
that of the earthworm Octolasium complanatum
460 kDa. Two different types of subunit have
been found in many, if not all, invertebrates, e.g.
in Clavarizona (28 and 25.5 kDa), in Octolasium
(20 and 19.7 kDa), and in the egg yolk ofthe snail
Lymnaea stagnalis (24 and 19 kDa); however,
comparison to the Hand L types of the mammals
is not reliable without sequence data [7, 131]. Of
the invertebrate ferritins mentioned above, only
that of L. stagnalis shows immunological crossreactivity to the ferritin of equine spleen [131].
Ferritin has been detected in the eggs and the
hepato-pancreas of various gastropods; this suggests that, like a typical yolk protein, ferritin is
produced in the hepato-pancreas and transported
in the blood to the oocytes. However, the subunits of egg ferritin in L. stagnalis are 24 kDa,
whereas those in the hepato-pancreas are 19 kDa
and have a different (cyanogen bromide) cleavage
peptide pattern; therefore, at least in this snail
species, the metabolic relationship between the
ferritins of the two organs is not at all clear [28].
References
1. Aketagawa J. et al.: Primary structure of Limulus
anticoagulant anti-lipopolysaccharide factor. J. biol.
Chern. 261: 7357-65 (1986)
2. Albers J. J. and SegrestJ. P. (eds.): Plasma lipoproteins. Acad. Press, New York 1986
3. Allen W. V. and Conley H.: Transport of lipids in the
blood of the Pacific oyster, Crassostrea gigas (Thunberg): Compo Biochem. Physiol. Pt. B 71: 201-207
(1982)