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10 mM) present in cyanobacteria, proteobacteria, a few Gram-positive
bacteria, as well as in all mitochondria or chloroplast-bearing eukaryotes
(
Masip et al., 2006
;
Zhang & Forman, 2012
). As summarized in
Fig. 5.1
,
GSH plays a central role in redox control of protein thiols and disulfide
bonds, as well as in protection against toxic metabolites (methylglyoxal
and formaldehyde), electrophiles, xenobiotics (
Cameron & Pakrasi, 2010
;
Masip et al., 2006
), antibiotics (
Cameron & Pakrasi, 2011
), and oxidative
and osmotic stresses (
Masip et al., 2006
). In addition, GSH operates in the
protection against arsenite (As(III)), a frequent pollutant. In response to As,
the yeast
Saccharomyces cerevisiae
exports and accumulates GSH outside the
cells where it conjugates with As forming the arsenite triglutathione com-
plex As(GS)3 that cannot enter cells, which are thereby protected from As
toxicity (
Thorsen et al., 2012
). GSH is also a key component of the cyto-
plasmic pool of labile iron, mostly occurring under the Fe(II)GSH complex
(
Hider & Kong, 2011
), which likely supplies Fe for the synthesis of the Fe
or (Fe-S) cluster cofactors of a wealth of enzymes involved in electron
transfers (photosynthesis respiration) and central metabolism. This finding
sheds light on the cross-talk between GSH and iron homeostasis, which are
especially important in cyanobacteria. Because they possess abundant Fe-
requiring machineries for photosynthesis, respiration and nitrogen assimila-
tion of cyanobacteria need an order of magnitude more Fe atoms within
their cells than heterotrophic bacteria (
Shcolnick, Summerfield, Reytman,
Sherman, & Keren, 2009
). Furthermore, Fe homeostasis and GSH play a
crucial role in the cyanobacterial defence against oxidative and metal stresses
(
Cameron & Pakrasi, 2010
;
Houot et al., 2007
;
Shcolnick et al., 2009
).
2.2. Biosynthesis of Glutathione
GSH is synthesized by the sequential action of two ATP-requiring enzymes
(
Fig. 5.2
), the γ-glutamyl-cysteine synthetase (GshA) enzyme, which catalyses
the addition of glutamic acid to cysteine to form the γ-glutamyl-cysteine
product, and the glutathione synthetase (GshB) enzyme, which adds glycine
to γ-glutamyl-cysteine to form GSH (
Masip et al., 2006
). In
Escherichia coli
,
GshA, the rate-limiting enzyme for GSH synthesis, is a monomer of 58.3 kDa,
while GshB is a tetramer with four identical subunits of 35.6 kDa (
Masip
et al., 2006
). GSH is dispensable in
E. coli
growing under laboratory condi-
tions (
Veeravalli, Boyd, Iverson, Beckwith, & Georgiou, 2011
), whereas it is
essential for cell growth in eukaryotes (
Spector, Labarre, & Toledano, 2001
).
The comparison of the highly divergent GshA sequences and the less
divergent GshB sequences suggests that the evolutionary history of their
