Limits...
Destroy and exploit: catalyzed removal of hydroperoxides from the endoplasmic reticulum.

Ramming T, Appenzeller-Herzog C - Int J Cell Biol (2013)

Bottom Line: Peroxidases are enzymes that reduce hydroperoxide substrates.Different peroxide sources and reducing substrates for ER peroxidases are critically evaluated.Peroxidase-catalyzed detoxification of hydroperoxides coupled to the productive use of disulfides, for instance, in the ER-associated process of oxidative protein folding, appears to emerge as a common theme.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstr. 50, 4056 Basel, Switzerland.

ABSTRACT
Peroxidases are enzymes that reduce hydroperoxide substrates. In many cases, hydroperoxide reduction is coupled to the formation of a disulfide bond, which is transferred onto specific acceptor molecules, the so-called reducing substrates. As such, peroxidases control the spatiotemporal distribution of diffusible second messengers such as hydrogen peroxide (H2O2) and generate new disulfides. Members of two families of peroxidases, peroxiredoxins (Prxs) and glutathione peroxidases (GPxs), reside in different subcellular compartments or are secreted from cells. This review discusses the properties and physiological roles of PrxIV, GPx7, and GPx8 in the endoplasmic reticulum (ER) of higher eukaryotic cells where H2O2 and-possibly-lipid hydroperoxides are regularly produced. Different peroxide sources and reducing substrates for ER peroxidases are critically evaluated. Peroxidase-catalyzed detoxification of hydroperoxides coupled to the productive use of disulfides, for instance, in the ER-associated process of oxidative protein folding, appears to emerge as a common theme. Nonetheless, in vitro and in vivo studies have demonstrated that individual peroxidases serve specific, nonoverlapping roles in ER physiology.

No MeSH data available.


Related in: MedlinePlus

The two-disulfides-out-of-one-O2 concept. O2 (red)-mediated oxidation of Ero1α results in the generation of one disulfide bond (red), which is transferred to a reduced PDI, and of one molecule of H2O2. ER-resident peroxidases (P)—probably exclusively of the GPx family (see main text for details)—can couple the reduction of Ero1α-derived H2O2 to H2O with the introduction of a second disulfide bond (red) into a PDI family member, thereby exploiting the oxidizing capacity of H2O2.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3824332&req=5

fig5: The two-disulfides-out-of-one-O2 concept. O2 (red)-mediated oxidation of Ero1α results in the generation of one disulfide bond (red), which is transferred to a reduced PDI, and of one molecule of H2O2. ER-resident peroxidases (P)—probably exclusively of the GPx family (see main text for details)—can couple the reduction of Ero1α-derived H2O2 to H2O with the introduction of a second disulfide bond (red) into a PDI family member, thereby exploiting the oxidizing capacity of H2O2.

Mentions: Oxidative protein folding relies on de novo disulfide generating enzymes and on oxidants, which accept the electrons derived from thiol oxidation. While several such electron transfer cascades exist in the mammalian ER, resulting in a certain degree of redundancy, Ero1 oxidases (using O2 as oxidant) and PrxIV (using H2O2 as oxidant) are evidently the dominant disulfide sources [29, 36, 81]. The fact that both enzymes can oxidize PDIs [75, 78, 81, 83, 97, 98] has led to the intriguing concept that the four oxidizing equivalents in O2 can be exploited by the consecutive activity of Ero1 and PrxIV to generate two disulfides for oxidative protein folding [79, 99] (Figure 5). Along the same lines, the PDI peroxidase activity of GPx7 constitutes a pathway for the productive use of Ero1α-derived H2O2 in the biosynthesis of disulfides [88, 89].


Destroy and exploit: catalyzed removal of hydroperoxides from the endoplasmic reticulum.

Ramming T, Appenzeller-Herzog C - Int J Cell Biol (2013)

The two-disulfides-out-of-one-O2 concept. O2 (red)-mediated oxidation of Ero1α results in the generation of one disulfide bond (red), which is transferred to a reduced PDI, and of one molecule of H2O2. ER-resident peroxidases (P)—probably exclusively of the GPx family (see main text for details)—can couple the reduction of Ero1α-derived H2O2 to H2O with the introduction of a second disulfide bond (red) into a PDI family member, thereby exploiting the oxidizing capacity of H2O2.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824332&req=5

fig5: The two-disulfides-out-of-one-O2 concept. O2 (red)-mediated oxidation of Ero1α results in the generation of one disulfide bond (red), which is transferred to a reduced PDI, and of one molecule of H2O2. ER-resident peroxidases (P)—probably exclusively of the GPx family (see main text for details)—can couple the reduction of Ero1α-derived H2O2 to H2O with the introduction of a second disulfide bond (red) into a PDI family member, thereby exploiting the oxidizing capacity of H2O2.
Mentions: Oxidative protein folding relies on de novo disulfide generating enzymes and on oxidants, which accept the electrons derived from thiol oxidation. While several such electron transfer cascades exist in the mammalian ER, resulting in a certain degree of redundancy, Ero1 oxidases (using O2 as oxidant) and PrxIV (using H2O2 as oxidant) are evidently the dominant disulfide sources [29, 36, 81]. The fact that both enzymes can oxidize PDIs [75, 78, 81, 83, 97, 98] has led to the intriguing concept that the four oxidizing equivalents in O2 can be exploited by the consecutive activity of Ero1 and PrxIV to generate two disulfides for oxidative protein folding [79, 99] (Figure 5). Along the same lines, the PDI peroxidase activity of GPx7 constitutes a pathway for the productive use of Ero1α-derived H2O2 in the biosynthesis of disulfides [88, 89].

Bottom Line: Peroxidases are enzymes that reduce hydroperoxide substrates.Different peroxide sources and reducing substrates for ER peroxidases are critically evaluated.Peroxidase-catalyzed detoxification of hydroperoxides coupled to the productive use of disulfides, for instance, in the ER-associated process of oxidative protein folding, appears to emerge as a common theme.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstr. 50, 4056 Basel, Switzerland.

ABSTRACT
Peroxidases are enzymes that reduce hydroperoxide substrates. In many cases, hydroperoxide reduction is coupled to the formation of a disulfide bond, which is transferred onto specific acceptor molecules, the so-called reducing substrates. As such, peroxidases control the spatiotemporal distribution of diffusible second messengers such as hydrogen peroxide (H2O2) and generate new disulfides. Members of two families of peroxidases, peroxiredoxins (Prxs) and glutathione peroxidases (GPxs), reside in different subcellular compartments or are secreted from cells. This review discusses the properties and physiological roles of PrxIV, GPx7, and GPx8 in the endoplasmic reticulum (ER) of higher eukaryotic cells where H2O2 and-possibly-lipid hydroperoxides are regularly produced. Different peroxide sources and reducing substrates for ER peroxidases are critically evaluated. Peroxidase-catalyzed detoxification of hydroperoxides coupled to the productive use of disulfides, for instance, in the ER-associated process of oxidative protein folding, appears to emerge as a common theme. Nonetheless, in vitro and in vivo studies have demonstrated that individual peroxidases serve specific, nonoverlapping roles in ER physiology.

No MeSH data available.


Related in: MedlinePlus