428
12 Small Nitrogenous Compounds
agnathans have a 3-8S form of about 160 kDa
which is replaced during metamorphosis by a 12S
form (in Petromyzon fluviatilis and Entosphenus
tridentatus) or a 19S form (in Lampetra reissneri).
Iodoproteins isolated from the thyroid of the
hagfish Eptatretus burgeri differ from thyroglobulin in many properties but can also form hormone, albeit at a lower efficiency. They contain
36-54 % carbohydrate (thyroglobulin <10 %)
and up to 5.9 % iodine (thyroglobulin <1 %), of
which, however, only 8-17% (thyroglobulin
20-40 %) is associated with hormone residues
[171].
The iodination of thyroglobulin-like proteins
has also been observed in the endostyle tissue of
the tunicates and acranians; this tissue is homologous to the thyroid. The production ofT4 and T3
has been confirmed in the acranians but is still
controversial in the tunicates. MIT and DIT are
also produced in the tunica of ascidians. However, it should be borne in mind that MIT and
DIT can arise in vitro in an oxidizing medium
through non-specific reactions with iodide ions;
this occurs especially in tyrosine-rich scleroproteins. Such processes have been observed in vivo in
representatives of practically all animal phyla.
The system of quinones and oxidases, as found in
sclerotizing structures, are particularly active in
this respect. However, T4 and T3 are produced
only in trace amounts, and these processes are
fundamentally different from those which occur
in the thyroid. Iodinated, but also brominated
and chlorinated, tyrosine derivatives are especially common in marine organisms.
More than 99 % of the thyroxin (T4) in the
blood is bound to plasma proteins. The most
important human T4-binding protein is the
thyroxin-binding globulin (TBG), a glycoprotein
of 54 kDa with 20 % carbohydrate. The T4binding pre-albumin (transthyretin) is also
important. Human TBG shows significant similarity in its sequence of 395 amino acids to the protease inhibitors al-antichymotrypsin and ar
antitrypsin but not to transthyretin [81]. TBG
appears to be the most important T4-binding protein of the mammals, but it is apparently absent
from some mammals and from birds and reptiles.
In the latter cases, the iodamino acids are bound
to albumin and pre-albumin. The blood plasma
iodamino acids are deiodinated in different tissues. The 3,5,3'-T3 produced by cleavage of the
iodine of T4 appears to be the actual hormonally
active substance, as the hormone receptors in the
cell nucleus have significantly higher affinities for
T3 than for T4. The T4 deiodination takes place
mainly in the liver, but also occurs in the kidneys
and other tissues. The mammals also produce the
isomer 3,3',5'-T3 (reverse T3)' which has no hormone activity, as well as several diiodothyronines.
In fish, on the other hand, only 3,5,3' -T3 has been
observed as the product of deiodination of T4 in
different tissues. In the anurans, the deiodination
of T4 greatly increases in intensity during metamorphosis. Deiodination of DIT and MIT takes
place in the liver of all classes of vertebrates, and
in urodelans and teleosts it also occurs in the kidneys [72]. The snakes lack the required enzymes
and their blood plasma contains correspondingly
higher concentrations of MIT and DIT [268]. The
elimination of the iodamino acids is mainly biliary, in the form of ~-glucuronides or sulphate
esters, and occurs in part after deiodination to
diiodothyronine.
U.6 Aromatic Amino Acids and the
Sclerotization of Insect Cuticulae
The diphenols (catechols) produced during the
metabolism of the aromatic amino acids phenylalanine and tyrosine have important functions as
neurotransmitters and neuromodulators, as precursors of the widely found pigment class of the
melanins, and as cross-linking structures for the
sclerotization of insect cuticulae and the tanning
of various proteins. The insects have received particular attention in this respect. The phenylalanine ingested by insects is rapidly hydroxylated to
tyrosine. The phenylalanine hydroxylase responsible for this process in insects, as well as in mammals, is an iron-containing, multifunctional oxygenase which requires a reduced pterin cofactor
and atmospheric oxygen. As shown by the cDNA
and gene sequences, phenylalanine hydroxylase
belongs to the same protein family as the corresponding enzymes that act on tyrosine and typtophan [32, 135]. In mammals, excess tyrosine is
deaminated by tyrosine transaminase to give
p-hydroxyphenylpyruvate; this is completely
catabolized by the opening of the benzene ring
with homogentisinic acid as an intermediate. This
transaminase is also present in insects. The
enzyme isolated from Drosophila hydei is very
similar to the mammalian enzyme. The tyrosine
metabolism of the blowfly Calliphora switches
over shortly before pupation. Instead of the predominant transamination to p-hydroxyphenylpyruvate, hydroxylation and decarboxylation
results in dihydroxyphenylalanine ( dopa) as the
12 Small Nitrogenous Compounds
agnathans have a 3-8S form of about 160 kDa
which is replaced during metamorphosis by a 12S
form (in Petromyzon fluviatilis and Entosphenus
tridentatus) or a 19S form (in Lampetra reissneri).
Iodoproteins isolated from the thyroid of the
hagfish Eptatretus burgeri differ from thyroglobulin in many properties but can also form hormone, albeit at a lower efficiency. They contain
36-54 % carbohydrate (thyroglobulin <10 %)
and up to 5.9 % iodine (thyroglobulin <1 %), of
which, however, only 8-17% (thyroglobulin
20-40 %) is associated with hormone residues
[171].
The iodination of thyroglobulin-like proteins
has also been observed in the endostyle tissue of
the tunicates and acranians; this tissue is homologous to the thyroid. The production ofT4 and T3
has been confirmed in the acranians but is still
controversial in the tunicates. MIT and DIT are
also produced in the tunica of ascidians. However, it should be borne in mind that MIT and
DIT can arise in vitro in an oxidizing medium
through non-specific reactions with iodide ions;
this occurs especially in tyrosine-rich scleroproteins. Such processes have been observed in vivo in
representatives of practically all animal phyla.
The system of quinones and oxidases, as found in
sclerotizing structures, are particularly active in
this respect. However, T4 and T3 are produced
only in trace amounts, and these processes are
fundamentally different from those which occur
in the thyroid. Iodinated, but also brominated
and chlorinated, tyrosine derivatives are especially common in marine organisms.
More than 99 % of the thyroxin (T4) in the
blood is bound to plasma proteins. The most
important human T4-binding protein is the
thyroxin-binding globulin (TBG), a glycoprotein
of 54 kDa with 20 % carbohydrate. The T4binding pre-albumin (transthyretin) is also
important. Human TBG shows significant similarity in its sequence of 395 amino acids to the protease inhibitors al-antichymotrypsin and ar
antitrypsin but not to transthyretin [81]. TBG
appears to be the most important T4-binding protein of the mammals, but it is apparently absent
from some mammals and from birds and reptiles.
In the latter cases, the iodamino acids are bound
to albumin and pre-albumin. The blood plasma
iodamino acids are deiodinated in different tissues. The 3,5,3'-T3 produced by cleavage of the
iodine of T4 appears to be the actual hormonally
active substance, as the hormone receptors in the
cell nucleus have significantly higher affinities for
T3 than for T4. The T4 deiodination takes place
mainly in the liver, but also occurs in the kidneys
and other tissues. The mammals also produce the
isomer 3,3',5'-T3 (reverse T3)' which has no hormone activity, as well as several diiodothyronines.
In fish, on the other hand, only 3,5,3' -T3 has been
observed as the product of deiodination of T4 in
different tissues. In the anurans, the deiodination
of T4 greatly increases in intensity during metamorphosis. Deiodination of DIT and MIT takes
place in the liver of all classes of vertebrates, and
in urodelans and teleosts it also occurs in the kidneys [72]. The snakes lack the required enzymes
and their blood plasma contains correspondingly
higher concentrations of MIT and DIT [268]. The
elimination of the iodamino acids is mainly biliary, in the form of ~-glucuronides or sulphate
esters, and occurs in part after deiodination to
diiodothyronine.
U.6 Aromatic Amino Acids and the
Sclerotization of Insect Cuticulae
The diphenols (catechols) produced during the
metabolism of the aromatic amino acids phenylalanine and tyrosine have important functions as
neurotransmitters and neuromodulators, as precursors of the widely found pigment class of the
melanins, and as cross-linking structures for the
sclerotization of insect cuticulae and the tanning
of various proteins. The insects have received particular attention in this respect. The phenylalanine ingested by insects is rapidly hydroxylated to
tyrosine. The phenylalanine hydroxylase responsible for this process in insects, as well as in mammals, is an iron-containing, multifunctional oxygenase which requires a reduced pterin cofactor
and atmospheric oxygen. As shown by the cDNA
and gene sequences, phenylalanine hydroxylase
belongs to the same protein family as the corresponding enzymes that act on tyrosine and typtophan [32, 135]. In mammals, excess tyrosine is
deaminated by tyrosine transaminase to give
p-hydroxyphenylpyruvate; this is completely
catabolized by the opening of the benzene ring
with homogentisinic acid as an intermediate. This
transaminase is also present in insects. The
enzyme isolated from Drosophila hydei is very
similar to the mammalian enzyme. The tyrosine
metabolism of the blowfly Calliphora switches
over shortly before pupation. Instead of the predominant transamination to p-hydroxyphenylpyruvate, hydroxylation and decarboxylation
results in dihydroxyphenylalanine ( dopa) as the