دورية أكاديمية
أعرض في EDS

Cystine rather than cysteine is the preferred substrate for β-elimination by cystathionine γ-lyase: implications for dietary methionine restriction.

التفاصيل البيبلوغرافية
العنوان: Cystine rather than cysteine is the preferred substrate for β-elimination by cystathionine γ-lyase: implications for dietary methionine restriction.
المؤلفون: Jeitner TM; Department of Radiology, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA. tmj4001@med.cornell.edu.; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, 10595, USA. tmj4001@med.cornell.edu., Azcona JA; Department of Radiology, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, 10595, USA., Ables GP; Orentreich Foundation for the Advancement of Science, Inc, 855 Route 301, Cold Spring, NY, 10516, USA., Cooke D; Orentreich Foundation for the Advancement of Science, Inc, 855 Route 301, Cold Spring, NY, 10516, USA., Horowitz MC; Department of Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, 06510, USA., Singh P; Department of Radiology, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA., Kelly JM; Department of Radiology, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.; Citigroup Biomedical Imaging Center, Weill Cornell Medicine, 516 East 72Nd St, New York, NY, 10021, USA., Cooper AJL; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, 10595, USA.
المصدر: GeroScience [Geroscience] 2024 Aug; Vol. 46 (4), pp. 3617-3634. Date of Electronic Publication: 2023 May 23.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101686284 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2509-2723 (Electronic) Linking ISSN: 25092723 NLM ISO Abbreviation: Geroscience Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cham : Springer International Publishing, [2017]-
مواضيع طبية MeSH: Cystathionine gamma-Lyase*/metabolism , Methionine*/metabolism , Cysteine*/metabolism , Cystine*/metabolism, Animals ; Male ; Liver/metabolism ; Liver/enzymology ; Hydrogen Sulfide/metabolism ; Kidney/metabolism ; Mice ; Rats
مستخلص: Dietary methionine restriction (MR) increases longevity by improving health. In experimental models, MR is accompanied by decreased cystathionine β-synthase activity and increased cystathionine γ-lyase activity. These enzymes are parts of the transsulfuration pathway which produces cysteine and 2-oxobutanoate. Thus, the decrease in cystathionine β-synthase activity is likely to account for the loss of tissue cysteine observed in MR animals. Despite this decrease in cysteine levels, these tissues exhibit increased H 2 S production which is thought to be generated by β-elimination of the thiol moiety of cysteine, as catalyzed by cystathionine β-synthase or cystathionine γ-lyase. Another possibility for this H 2 S production is the cystathionine γ-lyase-catalyzed β-elimination of cysteine persulfide from cystine, which upon reduction yields H 2 S and cysteine. Here, we demonstrate that MR increases cystathionine γ-lyase production and activities in the liver and kidneys, and that cystine is a superior substrate for cystathionine γ-lyase catalyzed β-elimination as compared to cysteine. Moreover, cystine and cystathionine exhibit comparable K cat /K m values (6000 M -1  s -1 ) as substrates for cystathionine γ-lyase-catalyzed β-elimination. By contrast, cysteine inhibits cystathionine γ-lyase in a non-competitive manner (K i  ~ 0.5 mM), which limits its ability to function as a substrate for β-elimination by this enzyme. Cysteine inhibits the enzyme by reacting with its pyridoxal 5'-phosphate cofactor to form a thiazolidine and in so doing prevents further catalysis. These enzymological observations are consistent with the notion that during MR cystathionine γ-lyase is repurposed to catabolize cystine and thereby form cysteine persulfide, which upon reduction produces cysteine.
(© 2023. The Author(s).)
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فهرسة مساهمة: Keywords: Cystathionine beta-synthase; Cystathionine gamma-lyase; Cysteine; Cystine; Methionine restriction; Transsulfuration
المشرفين على المادة: EC 4.4.1.1 (Cystathionine gamma-Lyase)
AE28F7PNPL (Methionine)
K848JZ4886 (Cysteine)
48TCX9A1VT (Cystine)
YY9FVM7NSN (Hydrogen Sulfide)
تواريخ الأحداث: Date Created: 20230522 Date Completed: 20240705 Latest Revision: 20240731
رمز التحديث: 20240731
مُعرف محوري في PubMed: PMC11229439
DOI: 10.1007/s11357-023-00788-4
PMID: 37217633
قاعدة البيانات: MEDLINE
الوصف
تدمد:2509-2723
DOI:10.1007/s11357-023-00788-4