کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2484822 1114338 2013 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Organic Nitrate Metabolism and Action: Toward a Unifying Hypothesis and the Future—A Dedication to Professor Leslie Z. Benet
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Organic Nitrate Metabolism and Action: Toward a Unifying Hypothesis and the Future—A Dedication to Professor Leslie Z. Benet
چکیده انگلیسی

ABSTRACTThis review summarizes the major advances that had been reported since the outstanding contributions that Professor Benet and his group had made in the 1980s and 1990s concerning the metabolism and pharmacologic action of organic nitrates (ORNs). Several pivotal studies have now enhanced our understanding of the metabolism and the bioactivation of ORNs, resulting in the identification of a host of cysteine-containing enzymes that can carry out this function. Three isoforms of aldehyde dehydrogenase, all of which with active catalytic cysteine sites, are now known to metabolize, somewhat selectively, various members of the ORN family. The existence of a long-proposed but unstable thionitrate intermediate from ORN metabolism has now been experimentally observed. ORN-induced thiol oxidation in multiple proteins, called the “thionitrate oxidation hypothesis,” can be used not only to explain the phenomenon of nitrate tolerance, but also the various consequences of chronic nitrate therapy, namely, rebound vasoconstriction, and increased morbidity and mortality. Thus, a unifying biochemical hypothesis can account for the myriad of pharmacological events resulting from nitrate therapy. Optimization of the future uses of ORN in cardiology and other diseases could benefit from further elaboration of this unifying hypothesis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 9, September 2013, Pages 3070–3081
نویسندگان
, ,