Chemistry Reference
In-Depth Information
symmetry (10, 11). Clusters can form aggregates, and other metal ions can replace
iron ions or can be present additionally.
Whereas many cognate apoenzymes can be reconstituted with iron/sulfur clus-
ters by simple and essentially alchemistic procedures using Fe
2
+
and sulfide ions
under anaerobic conditions, a highly complex enzymatic machinery is used
in vivo
for the synthesis of iron/sulfur clusters and their transfer to the target enzymes.
Sulfide ions required for cluster synthesis are obtained from cysteine (
1
)viaa
persulfide of a protein-bound cysteine residue (
2
); pyridoxal phosphate is required
for the formation of the persulfide intermediate (Fig. 10.1) (12).
In eukaryotes, the formation of iron/sulfur clusters proceeds inside mitochon-
dria (13). The mitochondrial enzymes are orthologs of the eubacterial
isc
proteins
and are characterized by very slow rates of evolution. Iron/sulfur clusters are ini-
tially assembled on IscU protein (prokaryotic) or Isu protein (eukaryotic) that
serves as a scaffold. They can be exported to the cytoplasm in which they can
become part of cytoplasmic enzymes by the assistance of proteins that serve as
iron chaperones.
The persulfide intermediate (
2
) can also serve as a sulfur source for the biosyn-
thesis of thiamine (
6
), lipoic acid (
7
), molybdopterin (
8
), and biotin (
9
) (Fig. 10.1).
10.2.2 Tetrapyrroles
A large and structurally complex family of coenzymes, including various hemes
and chlorophylls, and corrinoids, including coenzyme B
12
and the archaeal coen-
zyme F
430
, are characterized by their macrocyclic tetrapyrrole structure (14, 15).
These coenzymes contain a metal ion (Fe, Mg, Co, or Ni) at the center of the
tetrapyrrole macrocycle, which is specifically introduced by enzyme catalysis.
These compounds are all derived from
δ
-aminolevulinic acid (
12
) that can be
biosynthesized by two independent pathways, that is, from glycine (
11
)and
succinyl-CoA (
10
) in animals and some bacteria (e.g.,
Rhodobacter
)orfrom
glutamyl-tRNA (
13
) in plants, many eubacteria, and archaea (Fig. 10.2) (16, 17).
Twomoleculesof
-aminolevulinic acid (
12
) are condensed under formation
of porphobilinogen (
14
). Oligomerization of porphobilinogen affords hydrox-
ymethylbilane (
15
), in which all pyrrole rings share the same orientation of their
substituents. Ring D is then inverted by a rearrangement that affords uropor-
phyrinogen III (
16
) (3). Side-chain modification and the incorporation of iron by
ferrochelatase (18) afford the various heme cofactors, including heme a (
18
), that
carries an isoprenoid side chain. Starting from (
16
), a sequence of partial reduc-
tion, side-chain modification and incorporation of Mg
2
+
affords chlorophyll (
17
),
which also carries an isoprenoid side chain. Partial reduction, ring contraction,
and incorporation of Co
2
+
afford vitamin B
12
(
20
) as well as several analogs that
are found in archaea. Moreover, archaea incorporate nickel into the corrinoid
coenzyme F
430
(
19
) that plays a central role in the biosynthesis of methane (19).
Because plants are devoid of vitamin B
12
, the supply of humans and animals
is ultimately of bacterial origin (although humans can obtain vitamin B
12
via
δ
