Kinetics and mechanism of thermal decomposition of kynurenines and biomolecular conjugates: Ramifications for the modification of mammalian eye lens proteins

Kinetics and mechanism of thermal decomposition of kynurenines and biomolecular conjugates: Ramifications for the modification of mammalian eye lens proteins Full article

Journal

Organic and Biomolecular Chemistry
ISSN: 1477-0520 , E-ISSN: 1477-0539

Output data

Year: 2009, Volume: 7, Number: 14, Pages: 2958-2966 Pages count : 9 DOI: 10.1039/b903196k

Authors

Kopylova Lyudmila V. ² , Snytnikova Olga A. ² , Chernyak Elena I. ³ , Morozov Sergey V. ³ , Forbes Malcolm D.E. ¹ , Tsentalovich Yuri P. ²

Affiliations

1	(Данные Web of science) Univ N Carolina, Caudill Labs, Dept Chem, Chapel Hill, NC 27599 USA
2	(Данные Web of science) Russian Acad Sci, SB, Int Tomog Ctr, Novosibirsk 630090, Russia
3	(Данные Web of science) Russian Acad Sci, SB, Novosibirsk Organ Chem Inst, Novosibirsk 630090, Russia

Thermal degradation reactions of kynurenine (KN), 3-hydroxykynurenine (3OHKN), and several adducts of KN, to amino acids and reduced glutathione (GSH) have been studied at physiological temperature. These compounds are all implicated in age-related mammalian eye lens cataract formation at the molecular level. The main reaction pathway for both KN and 3OHKN is deamination via beta-elimination to carboxyketoalkenes CKA and 3OHCKA. These reactions show a weak pH dependence below pH values of similar to 8, and a strong pH dependence above this value. The 3OHKN structure deaminates at a faster rate than KN. A mechanism for the deamination reaction is proposed, involving an aryl carbonyl enol/enolate ion, that is strongly supported by the structural, kinetic, and pH data. The degradation of Lys, His, Cys and GSH adducts of the CKA moieties was also studied. The Lys adduct was found to be relatively stable over 200 h at 37 degrees C, while significant degradation was observed for the other adducts. The results are discussed in terms of known post-translational modi. cation reactions of the lens proteins and compared to incubation studies involving KN and related compounds in the presence of proteins.

Kopylova L.V. , Snytnikova O.A. , Chernyak E.I. , Morozov S.V. , Forbes M.D.E. , Tsentalovich Y.P.
Kinetics and mechanism of thermal decomposition of kynurenines and biomolecular conjugates: Ramifications for the modification of mammalian eye lens proteins
Organic and Biomolecular Chemistry. 2009. V.7. N14. P.2958-2966. DOI: 10.1039/b903196k WOS Scopus РИНЦ

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