Chemistry Reference
In-Depth Information
6.2.2 Non-Heme Iron Proteins
phosphate group transfers or hydrolysis seem to be
activated by Mg
2+
.
Non-heme iron proteins (e.g., rubredoxins, ferre-
doxins, hemerythrin, and high-potential iron proteins)
contain strongly bound functional iron atoms attached
to sulfur, but they do not contain porphyrins. All of
them have a role in electron transfer.
Ferritin and hemosiderin are important iron-con-
taining biological structures that both store iron in a
protein structure. Transferrin binds ferric iron and
transports it from ferritin to cells. In microorganisms,
iron is transported by ferrichromes and ferrioxamines,
structures containing cyclic or acyclic polypeptide
chains.
6.2.5 Metallothioneins
Metallothionein (MT) is a low molecular mass pro-
tein of approximately 6500 Dalton with a high content
of SH-groups from cysteine. Two distinct metal bind-
ing domains, the
-clusters have been charac-
terized in MT and are formed of the 61 amino acids
in human MT. The genes coding for metallothioneins
are present in most organisms, and their induction
after exposure to metals plays an important role in the
protection against metal toxicity. Both essential (zinc
and copper) and nonessential (cadmium and mercury)
metals can induce the synthesis of metallothioneins
and also constitute part of the molecule. Thus, these
proteins have a role in the metabolism of essential met-
als and protection against the toxicity of metals. The
four major groups of metallothioneins consist of MT-1,
-2, -3, and -4. Mammalian MT-1 and MT-2 are present
and expressed in almost all tissues. Only MT-1 exists
in many isoforms. MT-3 has seven additional amino
acids for a total of 68, with differences in charge char-
acteristics compared with MT-1 and MT-2. MT-3 was
identifi ed as a growth inhibitory factor (GIF) in brain.
MT-4 consists of 62 amino acids and has one glutamate
inserted. It is specifi c for squamous epithelium and
expressed in keratinocytes. The 14 human MT genes
are localized on chromosome 16q13-22. Of these, six
are functional, two are not, and six have not been char-
acterized. Metallothionein is important in the metab-
olism and kinetics of cadmium and copper, because
these metals are transported by MT in the organism.
Non-MT-bound cadmium is toxic and causes a toxic
insult to the cell. MT also serves various important
functions for zinc and mercury.
α
- and
β
6.2.3 Cobalt-Containing Biological Molecules
The best-known cobalt-containing biological mole-
cules are vitamin B
12
coenzymes (cobalamins). Cobala-
mins contain a cobalt atom, a macrocyclic ligand corrin,
and a complex organic part constituting a phosphate
group, a sugar, and an organic base also coordinated
to the cobalt atom. Methylcobalamin is involved in the
methane-producing bacteria and has been shown to
transfer the methyl (CH
3
) group to a number of metals
and metalloids, including Hg(II), Te(III), Pt (II), Au(I)
in vitro
. It is considered the most likely methylator of
mercury
in vivo
.
6.2.4 Metalloenzymes and Metal-Activated Enzymes
Some enzymes incorporate one or more metal
atoms in their normal structure. They are called met-
alloenzymes, including many zinc metalloenzymes.
The best known of these are carbonic anhydrase and
carboxypeptidase. The zinc ion is bound in a distorted
tetrahedral confi guration, with two histidine nitrogen
atoms, one glutamate carboxyl oxygen atom, and a
water molecule as ligands.
Another group consists of the copper-containing
metalloenzymes. Their structure is only known to a
limited extent. Ascorbic acid oxidase and various tyro-
sinases are examples of this group. In lower animals
(crabs, snails), the oxygen-carrying molecule is the
copper-containing protein hemocyanin, which, how-
ever, does not contain any heme groups (Lloyd
et al.
,
2005; Pallares
et al.
, 2005).
Metalloenzymes containing molybdenum and
iron (nitrogenases) play an important role in nitrogen
fi xation.
Metal ions can be bound to proteins in a reversible
way. This is the case with metal-activated enzymes.
Such systems are much less amenable to study than
metalloenzymes, because they cannot be isolated with
the metal in place. Most enzymes associated with
6.2.6 Lead-Containing Biological Molecules
-aminole-
vulinic acid dehydratase (ALAD) by specifi c binding.
Lead-binding proteins have been related to lead tox-
icity. For ALAD, genetic polymorphism is described.
The polymorphism is important with regard to lead
toxicity.
Lead is interfering with the enzyme
δ
7 TOTAL ELEMENT ANALYSIS, ELEMENTAL
SPECIATION, AND METALLOMICS
The adverse effects and toxicity of metals on a
living organism depend on (1) the quantity and the
chemical form
(species)
of the substance administered
or absorbed, (2) the way it is administered
(inhalation,
