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Biochemical and kinetic characterization of wild type and pathogenic mutant forms of human ETHE1
Author(s) -
Kabil Omer,
Banerjee Ruma
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.912.1
Subject(s) - sulfurtransferase , biochemistry , chemistry , enzyme , transsulfuration , mutant , cystathionine beta synthase , oxidoreductase , cysteine , wild type , metabolic pathway , gene
Hydrogen sulfide (H 2 S) is a recently described gaseous signaling molecule, which influences various cellular processes involving the central nervous system, cardiovascular system as well as mitochondrial energy metabolism. H 2 S is produced endogenously from the desulfhydration of cysteine and homocysteine by the enzymes of the transsulfuration pathway. Understanding the regulation of steady‐state H 2 S levels awaits biochemical characterization of the enzymes responsible for the oxidation and metabolic removal of H 2 S, sulfide quinone oxidoreductase, sulfur dioxygenase (ETHE1) and a sulfurtransferase. Mutations in the persulfide oxidizing enzymes, i.e. ETHE1, result in ethylmalonic encephalopathy, an autosomal recessive disorder. In this study, we report the biochemical characterization and kinetic properties of ETHE1 and describe the deficiencies associated with two patient mutations, T152I and D196N. Steady‐state kinetic analysis shows that T152I mutation results in 3‐fold lower activity, which is correlated with a 3‐fold lower iron content compared to wild‐type enzyme. The D196N mutation results in a 2‐fold higher Km for the substrate, glutathione persulfate (GSSH).