Chemistry Reference
In-Depth Information
THE BIOLOGICAL IMPORTANCE OF IRON
While iron readily undergoes electron transfer and acid
base reactions, it also has the capacity to participate in one
electron transfer (i.e. free radical) reactions. One such free radical reaction, essential for DNA synthesis, is the
reduction of ribonucleotides to the corresponding deoxy-ribonucleotides, catalysed by ribonucleotide reductases
(RNRs), all of which are radical metalloenzymes (
Nordlund & Reichard, 2006; Stubbe et al., 2001
)
. Since all
known cellular life forms store their genetic information in DNA, RNRs must be present in all growing cells of all
living organisms. They all catalyse the conversion of adenine, uracil, cytosine, and guanine nucleotides to deox-
ynucleotides, cleaving a 2
0
carbon
e
hydroxyl bond with formation of a 2
0
carbon
e
e
hydrogen bond (
Figure 13.2
).
FIGURE 13.2
The reaction catalysed by ribonucleotide reductases (RNRs).
(From
Stubbe, Ge, & Yee, 2001
.
Copyright 2001, with permission
from Elsevier.)
The hydrogen is derived from water and replaces the hydroxyl with retention of configuration. All RNRs share
a common catalytic mechanism involving activation of the ribonucleotide by abstraction of the 3
0
-hydrogen atom of
the ribose by a transient thiyl radical of the enzyme (
Figure 13.2
). Ribonucleotide reductases (RNRs) can be divided
into three classes, largely based on their interaction with oxygen and the way in which they generate the thiyl radical
required for ribonucleotide reduction. Class I RNRs contain two nonidentical dimeric subunits (R1 and R2) and
require oxygen to generate a stable tyrosyl radical through a Fe
Fe centre in the smaller R2 subunit. During
catalysis, the radical is continuously shuttled to a cysteine residue, some 30
˚
away in the larger R1 subunit where it
generates the thiyl radical (
Figure 13.3
). Almost all eukaryotes, from yeast to man, have Class I RNRs, as do a great
many eubacteria and a few archaebacteria. Class II RNRs (for example, in Lactobacillus species
1
)
are in different to
oxygen, contain a single subunit, and generate their thiyl radical using the Co(III) containing cofactor
adenosylcobalamine, probably via formation of a deoxyadenosyl radical. Class III RNRs are anaerobic enzymes,
inactivated by oxygen, which generate a glycyl radical, the counterpoint to the tyrosyl radical inClass I RNRs, through
a FeS cluster and S-adenosylmethionine. Whereas RNRs of class I and II use electrons from redox-active cysteines of
small proteins like thioredoxin or glutaredoxin, class III enzymes use formate as electron donor (
Figure 13.2
)
.
e
O
e
BIOLOGICAL FUNCTIONS OF IRON-CONTAINING PROTEINS
Iron-containing proteins can be classified according to a number of criteria
for example the functional role of
the metal ion, defined as (i) structural, (ii) metal storage and transport, (iii) electron transport, (iv) dioxygen
binding, and (v) catalytic
e
the latter being extremely large and diverse. As in the previous edition we have
chosen here a classification of iron metalloproteins based on the coordination chemistry of the metal. This has
the advantage of allowing the reader to more easily appreciate the diversity of biochemical functions in
which iron can participate, viewed through the ligands which bind it to the protein. We consider successively:
e
1. This may explain why this family of bacteria are found in dairy products, where the presence of lactoferriin makes iron availability
problematic. Class II RNRs are also found in some archaebacteria.
