Peroxiredoxins are ubiquitous group of cysteine dependent antioxidant enzymes found in both prokaryotes and eukaryotes help in regulating oxidative stress and modulates peroxide signaliing transduction.

1. MINOR CREDIT SEMINAR
Peroxiredoxins: Guardians against oxidative
stress and modulators of peroxide signalling
Submitted by: Arya Prakash Panda
Roll no-M-5687
Animal Biochemistry

3. Peroxire
doxins
Glutathi
one
peroxid
ase
catalase

4.  O2 + e− → ·O2
− (Reduction of molecular oxygen)
 2H+ + ·O2
− + ·O2
− → H2O2 + O2 (Peroxidation)
 H2O2 → HO · + ·OH (Partial Reduction)
 H2O2 + H2O2 → H2O + H2O + O2 (Fully Reduced)
Chemistry of Peroxides…

5. -Peroxiredoxins (Prxs) :Ubiquitous enzymes that have emerged as
most important and widespread peroxide scavenging enzymes in
all of biology.
-Cysteine based peroxidase enzymes that play a dominant role in
regulating cell peroxide levels.
Karplus,P.A(2014)Free Radic. Biol,Med. 80, 183-190
-Thiol specific antioxidant proteins termed as thiol redoxin
peroxidase.
-Not only acts as antioxidants but also appear to regulate H2O2
mediated signal transduction.
Wood, Z.A. et al(2003) Science 300,650-653
What are Peroxiredoxins?

6. E.C-1.11.1.15 according to HGNC.
Located primarily in cytosol
Recently cellular roles include modulation of H2O2
levels, which have been shown to mediate signaling
cascades leading to cell Apoptosis.
Wood,Z.A.et al. Science 300,650-653
Additional informations…..

7.  Prxs exist in six evolutionary subfamilies like Prx1, Prx5, Prx6,Tpx, PrxQ,
and AhpE.
 Prx1-highly expressed
-0.1–1% of the soluble protein in the cell
-typical 2-Cys Prxs (original type of ‘2-Cys Prx’having both a CP and CR
 In mammals, Prx1 subfamily enzymes divided into 6 groups( Prxs I-VI)
PrxI and PrxII (cytosol and nucleus )
PrxIII (mitochondria), PrxIV(ER), PrxV(peroxisomes,
mitochondria, and cytosol)
PrxVI, which is cytosolic .
 PrxQ,Prx5-Bacteria, Plant
 Tpx & AhpE-Bacteria
 Prx(I-IV)-Typical 2-Cys, PrxV-Atypical 2-Cys, PrxVI-1 Cys
Rhee S, Chae H, Kim K (2005). Free Radic .Biol Med 38 (12): 1543–52.
Classification

8. Wood ZA, et al. Trends Biochem. Sci. 28 (1): 32–40.

9. Mechanism
Perkins A et al. Trends in Biochem. Sci. 40 (8): 435–445

10. Conformational changes
Wood ZA, Schröder E, Harris JR, Trends Biochem Sci. 2003; 28:32–40.

12.  It is the state in which oxidation exceeds the antioxidant
systems in the body secondary to a loss of the balance
between them.
 Imbalance between oxidants(ROS) and antioxidants(Prx,
catalase, Gpx)
Oxidative stress

13. OXIDATIVE STRESS

14.  Reduce >90% of cellular peroxides.
 Can detect less concentration like 10 μM H2O2 in
cell.
 Some eukaryotic Prxs are inherent to
hyperoxidative inactivation by H2O2
Prxs in Stress…
Perkins A et al. Trends Biochem. Sci. 40 (8): 435–445

15.  Not only oxidative stress defense enzymes but also
regulators of peroxide levels in cells in stress response
signaling.
 Act as 2nd messenger in GF signalling, angiogenesis.
 NADPH oxidase complex(Nox) are the source.
Localization of H2O2
mediated Signaling process
Woojin Jeong, Tong-Shin Chang et al. Current Opinion in Cell Biology 2005, 17:183–189

16.  Protein tyrosine phosphatase(PTP) and Phosphatase Tensin
homolog lipid phosphatase (PTEN) which is regulated by Prxs.
PTPs-Proteins of low pKa of 4.7-5.4 Cysteine residues.
It Undergoes H2O2 dependent inactivation in cells (Cys–S to
Cys–SOH).
PTEN is a member of PTP family oxidised by H2O2 to
intramolecular disulfide with Cys71 So oxidative inhibition of
PTEN.
Target molecules
Sue Goo Rhee et al Current opinion in cell Bio. 17 (2): 183-189

17. PTP
www.fibrogenesis.com

18. PTEN
jcs.biologists.org

19. Reversible inactivation of PTPS &
PTEN in cells
Kang W.S et al Current opinion in cell Bio. 17 (2): 183-189

20. Elimination of H2O2 by Prxs

21. Prxs ubiquitous group of antioxidant enzymes contain
conserved Cys residues present in cytosol,mitochondria,
ER as well as Nucleus.
Plays important role in maintaining peroxide levels in cell
as well as function as a guard against oxidative stress.
Plays a key role in signaling.
Conclusion

22.  Karplus,P.A, A primer on perxiredoxin biochemistryFree
Radic. Biol,Med. 80, 183-190(2014)
 Wood, Z.A, Peroxiredoxin evolution and the regulation of
hydrogen peroxide signaling. Science 300, 650–653(2003)
 Woo, H.A., Reversing the inactivation of peroxiredoxins
caused by cysteine sulfinic acid formation. Science 300, 653–
656 ( 2003)
 Perkins A, Peroxiredoxins: guardians against oxidative stress
and modulators of peroxide signaling Trends Biochem.
Sci. 40 (8): 435–445(2015)
 Rhee S.G., Intracellular messenger function of hydrogen
peroxide and its regulation by peroxiredoxins, Current
opinion in cell Bio. 17 (2): 183-189(2005)
REFERENCES

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