Plants Electron transfer

Animals O
2
-carrying
Protection of DNA from O
2
-
Cu-proteins and enzymes
Cytochrome oxidase O
2
H
2
O
Tyrosinase, phenol oxidase oxidation of phenols
Ceruloplasmin Fe(II) Fe(III)
Blue proteins Electron transfer
Superoxide dismutase Elimination of O
2
-
Hemocyanin O
2
transport
Bioinorganic Chemistry Copper (I, II)
10/10/2014 CH-101 2
Absorption of copper
Cu is absorbed by the body at two main sites:
- small intestine
- stomach
The gateway is a copper "transporter," a specific pore on the surface
of intestinal cells that funnels copper inside the intestinal walls.
From there, copper is absorbed by the bloodstream and distributed
throughout the body.
Copper absorption may be decreased by excess dietary Iron or Zinc.
Bioinorganic Chemistry Copper
10/10/2014 CH-101 3
Transport of absorbed copper
Cu does not float through the bloodstream as a lone copper ion but is
carried by proteins. Two main carrier proteins are
- ceruloplasmin (specifically for copper)
- albumin (can carry many things including copper)

Copper Storage
Cu is stored by a family of proteins called metallothioneins
Copper is stored in the liver and excreted in bile salts
Bioinorganic Chemistry Copper
10/10/2014 CH-101 4
The enzyme cytochrome c oxidase or Complex IV is a large transmembrane
protein found in bacteria and the mitochondrion.
The complex contains two hemes Cytochrome a and Cytochrome a
3
Two copper centers Cu
A
and Cu
B
Bridged by Hydroxide ion
Cytochrome c oxidase
Summary reaction:
4 Fe
2+
-cytochrome c + 8 H
+
in
+ O
2
4 Fe
3+
-cytochrome c + 2 H
2
O + 4 H
+
out
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SOD catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide.
It is an important antioxidant.
Superoxide dismutase (SOD)
SOD-Cu
2+
+ O
2
.-
SOD-Cu
1+
+ O
2
SOD-Cu
1+
+ O
2
.-
+ 2H
+
SOD-Cu
2+
+ H
2
O
2

10/10/2014 CH-101 6
It is an enzyme that converts dopamine to norepinephrine (neurotransmitters).
DBH is a 290 kDa copper-containing oxygenase enzyme
It is made of four identical subunits
Its activity requires ascorbate as a cofactor
Dopamine b-hydroxylase
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Ceruloplasmin is known as ferroxidase or iron(II):oxygen
oxidoreductase.
It is an enzyme synthesized in the
liver containing 8 atoms of copper.
Ceruloplasmin carries 90% of the
copper in our plasma.
The other 10% is carried by
albumin.
It exhibits a copper-dependent
oxidation of Fe
2+
to Fe
3+
.
Ceruloplasmin
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Lysyl oxidase
Lysyl oxidase is an extracellular enzyme.
It catalyzes formation of
aldehydes from lysine residues in
collagen and elastin precursors.
These highly reactive aldehydes
undergo spontaneous reactions
with other aldehyde or lysine
residues. This results in cross-
linking collagen and elastin
which is essential for stabilization
of collagen fibrils and for the
integrity and elasticity of mature
elastin.
Lysine residues
Lysyl Oxidase
Aldehyde derivatives
Aldol cross link product
10/10/2014 CH-101 9
Hemocyanins are respiratory proteins containing two copper
atoms that reversibly bind a single oxygen molecule.
Oxygenation causes a color change



Hemocyanins carry oxygen in the blood of
most molluscs, and some arthropods.
b-sheet
a-helix
Cu
1
Cu
2
O
O
Hemocyanin
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Fe (III) is the oxidation state of the bound iron.
An extremely stable complex must be formed for transport across
membranes.
Free iron is extremely toxic.
A chelate type ligand with hard oxygen donors is used.
The iron(III) ion is bound in its preferred octahedral coordination
geometry.
In biology three steps are involved in Iron chemistry:
Uptake
Transport
Storage
Bioinorganic Chemistry Iron
10/10/2014 CH-101 11
Siderophores (microorganisms) for uptake by two groups of chelating agents.
Hydroxamate
Catecholate
Synthetic analogues have been prepared to combat -thalassemia which prevents
haemoglobin manufacture and results in iron overload.
Ferrichrome
Iron Uptake
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Transfer of Iron is mainly done by Transferrin
Proteins (large-80 kilodaltons) in the transferrin tightly bind Fe(III) K =
10
20
M
-1
Stability of complexes decrease with decreasing pH
Uptake of two Fe(III) and one HCO
3
-

Not very specific (Cr
3+
, Al
3+
, Cu
2+
, Mn
2+
)
Release of Fe(III): Reduction to Fe(II) and binding by porphyrine
The released iron is available for use or can be put into storage (ferritin).
Iron Transport
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It is spherical protein made of 24 subunits (inner dia.: ~ 7 nm, outer dia. ~
13 nm)
The inside of the protein is lined with hydrophilic residues of Carboxylate
groups for Fe(III) binding.
Exchange via channels (dia. 1nm), tuning of hydrophilic/hydrophobic
character via residues
Release of Fe as Fe(II) via hydrophilic channels
Iron Storage
Iron storage is performed by protein Ferritin
Ferritin is a biological storage protein that can
accommodate up to 4,500 iron atoms in a ferric
oxide core.
It is a made of highly symmetric Apoferritin
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What form does the iron core take?
Spectroscopic results (EXAFS, Mossbauer and
UV/vis.) suggest octahedrally coordinated Fe(III) joined
by bridging hydroxide and/or oxide ions.
Most consistent with a close packed array of oxygen
atoms with Fe occupying the octahedral holes
Formation of the ferritin core is a process termed
biomineralisation
Core-structure related to Ferrihydrite Fe
10
O
6
(OH)
18
Iron Storage
Ferritin
Apoferritin
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Hemoglobin (Hb) is the iron-containing oxygen-transport metalloprotein in the red
blood cells of the blood in vertebrates and other animals. It is tetrameric.
Hemoglobin = Heme (or haem) + Globin (globular protein)
Hemoglobin
Heme group
The protein subunits are in red and blue, and
the iron-containing heme groups in green
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Myoglobin is a single-chain globular protein of 153 amino acids. It is
monomeric.
Contains a heme prosthetic group in the center surrounded by apoprotein.
Molecular weight of 16,700 daltons
It is the primary oxygen-carrying pigment of muscle tissues.
Myoglobin
O
2
Fe
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The oxygen binding site is a binuclear iron center.
The iron atoms are coordinated to the protein through the carboxylate side chains
of a glutamate and aspartate and five histidine residues.
Hemerythrin and myohemerythrin are often described according to oxidation and
ligation states of the iron center.
Hemerythrin
Fe
2+
OHFe
2+
deoxy (reduced)
Fe
2+
OHFe
3+
semi-met
Fe
3+
OFe
3+
OOH
-
oxy (oxidized)
Fe
3+
OHFe
3+
(any other ligand) met (oxidized)


Fe
H
O
Fe
deoxy
O
2
Fe
O
Fe
O
O
H
oxy
Fe
O
Fe
O
OH