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Protein 1 -SH + Protein 2 -SH + H 2 O 2 → Protein 1 -S-S-Protein 2 + 2H 2 O
Reaction 47
FIG. 1.19 An exposure of the protein OxyR to hydrogen peroxide (H 2 O 2 ) converts
Cys 199 to a sulfenic acid derivative that forms an intramolecular disulfide bond with
Cys 208 .
plasma. All these molecules are metabolically interrelated and are important
in determining the redox environment and free-radical interactions (541, 542).
Cys is unstable and toxic at high concentration; however, cells and tissues have
an absolute requirement for it, and plasma GSH seems to be a critical source
for maintaining steady Cys availability. Cys may also derive from intracellular
stores of various tissues (e.g., skeletal muscle during starvation) that can
deliver it to the plasma; the other main source is diet (543). Methionine can
also serve as a source of Cys because it can be converted to this amino acid
through the transsulfuration pathway. Hcys does not derive directly from GSH
but is an intermediate in the transformation of methionine into Cys, and is
probably delivered by all those cells capable of performing the transsulfura-
tion pathway reactions (544). Human plasma contains GSH, Cys, CysGly, and
Hcys in the 0.1- to 20-
M range (541). These thiols can also be found in disul-
fide forms, both as low-molecular-mass disulfides (LMM-SS) and as protein/
LMM-SH mixed disulfides. Usually, disulfide forms (with the exception of
glutathione disulfide [GSSG]) are more concentrated than the respective thiol.
Considering the total concentration for each thiol species (i.e., reduced
μ
disul-
fide forms), Cys is usually present at the highest concentration, with CysGly,
Hcys, and GSH (545). Additionally, the ratio Cys/cystine is significantly shifted
to the oxidized species with respect to the ratio GSH/GSSG, suggesting that
these may represent two pools with distinct regulation and significance
(542).
Giustarini et al. 2006 (546) have focused on plasma thiols to assess whether
during aging there is a shift in the thiol/disulfide balance, and found evidence
for the age-related variation in the relative percentages of all thiol forms (i.e.,
reduced, disulfide, and protein-mixed disulfides). A study was published in
which all redox forms of plasma thiols have been investigated in relation to
aging in the age range of 21-92 years. The data show that a strong inverse
correlation exists between aging and levels of CysGly and GSH, whereas
neither their disulfides nor tGSH and tCysGly changed. Conversely, direct
correlations were found between the disulfide forms of Cys and Hcys and age.
As expected, the concentration of protein SH groups decreased with age, as a
consequence of the increased levels of mixed disulfides with Cys and Hcys,
and the decline of the plasma concentration of albumin that takes place in
elderly persons (547). It has also been observed in previous work that an
oxidative shift of Cys and GSH toward disulfide forms occurs in human plasma
in elderly persons (543, 548).
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