Chemistry Reference
In-Depth Information
and II) to give a heterodimer. When exposed to oxygen or superoxide (step III), a disulfide is formed within the
heterodimer, which subsequently undergoes disulfide isomerisation to an intramolecular disulfide in SOD1 (step
IV). At some point after the introduction of oxygen, copper is transferred from the chaperone to the SOD1. The
mature monomeric SOD1 is then released from the CCS chaperone and dimerizes to its active form.
We discuss briefly now how metals are incorporated into porphyrins and corrins to form haem and other
metallated tetrapyrroles, and how Fe
S clusters are synthesised.
e
CHELATASE
e
THE TERMINAL STEP IN TETRAPYRROLE METALLATION
Tetrapyrroles are organic molecules that contain four five-membered heterocyclic (pyrrole) rings, linked in
a cyclic or linear array. Haem, chlorophyll, cobalamin (vitamin B
12
), siroHaem,
6
and coenzyme F
430
belong to
a family of prosthetic groups that are characterised by their tetrapyrrole-derived nature and contain a central,
complexed metal ion: Fe
2
þ
in haem and siroHaem, Mg
2
þ
in chlorophyll and bacteriochlorophyll, Co
2
þ
in
cobalamin, and Ni
2
þ
in coenzyme F
430
They are all derived from a common tetrapyrrole precursor, uropor-
phyrinogen III (
Fig. 4.8
). The insertion of each of these metal ions involves a group of enzymes called chelatases,
of which the best characterised is ferrochelatase, which inserts Fe
2
þ
into protoporphyrin IX in the terminal step of
FIGURE 4.8
The tetrapyrrole biosynthetic pathways. Chelatases selectively insert Fe
2
þ
to form haem, Mg
2
þ
to form chlorophyll, Co
2
þ
to
form cobalamine, and, in methane-producing bacteria, Ni
2
þ
to form coenzyme F
430
.
the haem biosynthetic pathway. The different chelatases are thought to have similar mechanisms, which involve as
the first step the distortion of the tetrapyrrole porphyrin upon binding to the enzyme to give a saddled structure
(
Fig. 4.9
a) in which two opposite pyrrole rings are slightly tilted upwards while the other two pyrrole rings are
tilted slightly downwards. In
Fig. 4.9
a
, the two unprotonated nitrogen atoms of the pyrrole rings point upward,
while the two protonated nitrogens point downward with respect to the porphyrin ring. Subsequent to the
distortion of the porphyrin ring, the first metal
porphyrin bond is formed (
Fig. 4.9
b), followed by other ligand
exchange steps leading to formation of a complex in which the iron atom is sitting on top of the porphyrin, with
two of its nitrogen atoms coordinated to the metal while the other two are still protonated. This is followed by the
e
6. Sirohaem is a tetrahydroporphyrin which has adjacent reduced pyrrole rings and is present in bacterial sulfite and nitrite reductases.
