Reactions of 4-Hydroxy-2(E)-nonenal and Related Aldehydes with Proteins Studied by Carbon-13 Nuclear Magnetic Resonance Spectroscopy

详细信息    查看全文

• 作者：Venkataraman Amarnath ; William M. Valentine ; Thomas J. Montine ; William H. Patterson ; Kalyani Amarnath ; Casey N. Bassett ; and Doyle G. Graham
• 刊名：Chemical Research in Toxicology
• 出版年：1998
• 出版时间：April 1998
• 年：1998
• 卷：11
• 期：4
• 页码：317 - 328
• 全文大小：222K
• 年卷期：v.11,no.4(April 1998)
• ISSN：1520-5010

文摘

In order to understand the modifications of proteins produced byaldehydes of lipidperoxidation, [1-¹³C]-2(E)-hexenal,[1-¹³C]-4-oxopentanal, and a mixture of[1-¹³C]- and [2-¹³C]-4-hydroxynon-2(E)-enal were synthesized and the reaction ofeach of the labeled aldehydeswith bovine serum albumin was analyzed by ¹³C NMRspectroscopy. Protein nucleophiles addto the 3-position of hexenal, and the resulting propanal moietiesappear to undergo aldolcondensation, form imine cross-links with lysyl residues, or lead topyridinium rings. Duringthe reaction of 4-oxopentanal with the lysyl residues of bovine serumalbumin, only 1-alkyl-2-methylpyrrole and a possible intermediate leading to the pyrrole wereobserved. Hydroxypyrrolidine cross-links such as 25 could not be detected,leaving the pyrrole as the mediator ofprotein cross-linking. The Michael adducts are the major productsin the reaction between4-hydroxynon-2-enal and proteins. They exist almost exclusively inthe cyclic hemiacetal formand do not appear to cross-link through imine formation with lysylresidues. A minor pathwayinvolves the reaction of 4-hydroxynon-2-enal with the lysyl aminogroups of protein resultingin 2-pentylpyrrole adducts that may mediate protein cross-linking.The Michael adducts appearnot to be the direct source of the pyrrole, but the imine 32and the enamine 35 are likelyintermediates toward the five-membered ring.