Antioxidant Enzymes
Fatima Cabral
Masaaki Ishii
Beatrice Lazzaretto
Axel Leppert
Yizi Mao
(https://www.quora.com/How-does-DNA-get-damaged-by-reactive-oxygen-species)
(https://www.intechopen.com/books/current-issues-in-sports-and-exercise-medicine)
(https://www.intechopen.com/books/current-issues-in-sports-and-exercise-medicine)
Superoxide
• Reactive oxygen species (ROS)
• Superoxide source
– Bacteria: Reduced flavin, NADPH
oxidase.
– Plants: Photosystem I and reduced
plastoquinones
– Animals: e.g. mitochondrial respiration
Superoxide dismutase (SOD)
• Antioxidant proteins
• Detoxify superoxide
–Catalyze the dismutation of O2·–Transfer an electron from one
superoxide to another
O2·-  H2O2 + O2
–Preventing undesired side reactions.
SOD in signaling
• Protect iron-sulfur cluster binding
signaling proteins
• H2O2 :
– Oxidize protein
– Regulate oxidative stress defense system
– Fe(II) can target specific sites reduce H2O2
into HO- plus HO• to cause damage
Types of SOD
▪ Cu, Zn SOD
• homodimeric, Cu (II) in one subunit, Zn (II) in the other
• Cu (II) is the catalytic center, Zn (II) has structural and facilitative role
• Cytosol, intermembrane space in mitochondria, extracellular (eukaryota); cytosol,
periplasm (gram negative bacteria)
▪ Mn SOD
• Homotetrameric (human); dimeric (E. coli)
• Mitochondrial matrix (eukaryota), cytosolic (E.coli)
• Can be upregulated by O2.- in E.coli
▪ Fe SOD
• Not found in animals
• Cytosolic (E. coli); cloroplasts (plants)
▪ Cambialistic SOD
• Found in anaerobic bacteria
• Can operate with either Mn (III) or Fe (III) at the active site
▪ Ni SOD
• Homotetrameric
• Found in Streptomyces
• inducible by Ni-enriched growth media
E. coli
B. subtilis
S. cerevisiae
H. sapiens
isofroms
3 (sodA, sodB,
sodC)
1 (sodA)
2 (sod1, sod2)
3 (SOD1, SOD2,
SOD3)
types
MnSOD, FeSOD,
Cu,ZnSOD
MnSOD
Cu,ZnSOD,
MnSOD
Cu,ZnSOD,
MnSOD
cellular
localization
cytosolic + DNA
interacting
(MnSOD);
cytosolic,
membrane
proximity (FeSOD);
periplasm
(Cu,ZnSOD)
cytosolic
mitochondrial
(MnSOD);
cytosolic
(Cu,ZnSOD)
mitochondrial
matrix (SOD2MnSOD);
cytosolic (SOD1Cu,ZnSOD);
extracellular
(SOD3Cu,ZnSOD);
references
▪
•
▪
▪
▪
▪
Takeda Y., Avila H. 1986. Nucl
eic Acids Res. 14:4577–4589.
Carlioz A. et al. 1988 J. Biol.
Chem.263:1555–1562.
Benov L. T., Fridovich I. 1994.
J. Biol. Chem. 269:25310–
25314.
•
Liu P et al. Acta
Crystallographica
Section F: Structural
Biology and
Crystallization
Communications.
2007;63(Pt 12):10031007
Inaoka T et al. J.
Bacteriol. 1998 vol.
180no. 14 3697-3703
BerminghamMcDonogh, O. et al.
1988 Proc. Nati. Acad.
Sci. USA 85, 4789-4793
Abreu, I.A., Cabelli, D.E.
2010 Biochim Biophys
Acta. 1804: 263-274
How many catalase genes?
• In E. Coli,
– KatE, KatG, katP, EHEC-catalase, EC-catalase,
ECs1652 etc, 15 genes
• B. Subtilis,
– KatA, KatE, KatX, etc, 8 genes
• S. Cerevisiae,
– CTT1, CD36, 2 genes
• Human,
– CAT, 1 gene
What cofactor does catalase require?
• Heme (iron) – Fe(IV)
2H2O2 -> 2H2O + O2
((1))
((2))
Where are the catalase enzymes localized?
• Catalase is usually located in a cellular, bipolar
environment organelle called the
Peroxisome
Liver cell
Are there any diseases or phenotype
associated with lack of catalase?
• Acatalasemia: lack of catalase caused by
mutation of CAT.
– Type II diabetes
– Mouth Ulcer
Peroxiredoxins
Prx 4 – decamer; PDB: 2PN8
Substrates
Peroxynitrite
Organic hydroperoxides
H2O2
Catalytic cycle
Peroxidatic Cys (CP):
Sensitive to oxidation
by peroxides
Resolving Cys (CR):
Forms a disulfide
bond with CP
Perkins et al., Trends in Biochem. Sc., 2015
Prx-classification
1-Cys (Prx 6)
Atypical 2-Cys (Prx 5)
Typical 2-Cys (Prx 1-4)
Nicolussi et al., Molecular and Clinical Oncology, 2017
Cellular Localization
Valero et al., Biologie, 2015
• Glutathione peroxidase features a selenocysteine
residue in it’s active site
• It exists in 8 isoforms involved in reducing hydrogen
peroxide to water as well as reducing lipid
peroxidases to water
Glutathione peroxidase 4
• Glutathione Peroxidase degrade oxidative species in the
cell using glutathione as a substrate for electron
donation
H2O2
2(
)
2H2O +