Discovery of an Accretion Streamer and a Slow Wide-angle Outflow around FUOri...
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1. Despite over half a century of research,
the exact functions of MTs are still under
debate. Due to the high kinetic mobility
of metals within metal clusters, MTs are
involved in trace metal exchange
(binding/release). The main hypothesized
functions are:
(1) homeostasis of the essential trace
metals Zn and Cu;
(2) detoxification of the non-essential
metals Cd and Hg;
(3) donation of essential metals to apo
metalloproteins;
(4) protection against oxidative damage;
(5) free radical scavenger as thionein;
last but not least, MT could be a
multifunctional protein.
The biological role of MTs
Advanced Inorganic Chemistry 1
Master in Chemistry
Prof.ssa Daniela Valensin
2. Their basic functions depend on the organism and the peptide variants:
As metal storing proteins they participate in the homeostasis of metal ions first
of all that of copper and zinc.
As detoxification molecules they are active in the removal of detrimental soft
metal ions (such as CdII, HgII, AgI and AuI).
Their synthesis is induced by some essential, Zn and Cu, but some toxic metal
ions, Cd, too.
Inorganic-Hg does, but organic-Hg does not induce formation of
metallothioneins.
Biological role of MTs
Advanced Inorganic Chemistry 1
Master in Chemistry
Prof.ssa Daniela Valensin
3. A metallothioneins occur in human, in animals and
plants (phytochelatins), they are low molecular
mass (6-7 kDa) proteins, which bind soft metal ions
(CuI, ZnII, CdII, Hg2
II, HgII, AgI and CoII) in cluster
structure. Their sulphur and metal contents are
very high, may reach 10%.
Generally they consisit of two clusters, in which the
metal ions coordinate through Cys-thiolates. The
polypeptid part features repeated Cys-X-Cys
sequences. In the middle of the Figure 12 terminal
and 8 bridging CYS side chain bind all together 7
Cd2+-ions, in a chair conformation [3M-3S] cluster
(Cd3S9) and an adamantane conformation [4M-5S]
cluster (Cd4S11).
Metal Detoxification
Advanced Inorganic Chemistry 1
Master in Chemistry
Prof.ssa Daniela Valensin
6. (a) Entering of metal ions into a cell.
(b) The ions interact with metal
synthesis inhibitor (MTI).
(c) Released metal transcription
factor 1 (MTF-1) binds to metal
responsive element (MRE).
(d) Synthesis of mRNA to translate
MT.
(e) MT binds a heavy metal ion, the
MT–heavy-metal-ion complex is
transported to kidney or (f) to
heavy metal dependent
regulation proteins.
MTF-1
Heavy metals (Zn, Cd, Pb, Cu ?)
?
Phosphorylation?
Nucleus
Cytoplasm
MRE
mRNA
MT
MTF-1
MTI
MTI
MT
excretion
kidney
(a)
(b)
(c)
(d)
(f)
(e)
MTF-1
Metal Detoxification
Advanced Inorganic Chemistry 1
Master in Chemistry
Prof.ssa Daniela Valensin
7. Metallothionein scavenging of reactive oxygen species.
Presence of redox metals, such as Cu and Fe, in a cell can produce reactive oxygen species
(ROS), leading to damaging of DNA and cell structures.
The cell protects itself using various molecules as scavengers of the radicals.
One of the most crucial cell pathways to scavenge the radicals is the glutathione redox
complex.
However, free –SH moieties of MT can be also involved in the scavenging of ROS in the MT
redox cycle. Under physiologic conditions, zinc bound to MT is released through oxidation of
the thiolate cluster when the environment becomes oxidized. Formation of MT-disulfide
would be subjected to degradation; however, when the oxidized environment became
reduced—through, for example, an increase in the glutathione (GSH)/glutathione disulfide
(GSSG) ratio—MT disulfide is reduced to MT-thiol. This reduction process is greatly
enhanced in the presence of selenium catalyst. In the presence of zinc, MT is quickly
reconstituted. This process constitutes the MT redox cycle, which plays a crucial role in the
biologic function of MT.
Metal Detoxification
Advanced Inorganic Chemistry 1
Master in Chemistry
Prof.ssa Daniela Valensin
8. MRE
MTF-1
(d)
Nucleus
Cytoplasm
(a)
(b)
(c)
MT
S
S
H2O2
●OH
Reactive oxygen
species (ROS)
GSSG
GSH
DNA damage
MT
S
S
MT
S
S
Cell damage
MT
S
S
MT
S
S
Reactive
oxygen
species
Heavy metals (Zn, Cd,
Pb, Cu ?
(a) Presence of heavy
metals in a cell can
produce reactive oxygen
species (ROS).
(b) To scavenge ROS
glutathione and MT can
be used.
(c) Free heavy metal ions
lead to activation of
MTF-1 → to synthesis of
MT.
(d) MT can bind metal ions
and scavenge ROS.
Metal Detoxification
Advanced Inorganic Chemistry 1
Master in Chemistry
Prof.ssa Daniela Valensin
