| Indispensable but insufficient role of renal D-amino acid oxidase in chiral inversion of NG-nitro-D-arginine. | |
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MedLine Citation:
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PMID: 20564560 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Unidirectionally chiral inversion of N(G)-nitro-D-arginine (D-NNA) to its L-enantiomer (L-NNA) occurred in rats, and it was blocked markedly (ca. 80%) by renal vascular ligation, and entirely (100%) by the D-amino acid oxidase (DAO) inhibitor sodium benzoate, suggesting that renal DAO is essential for the inversion. However, the doses of sodium benzoate administrated were extremely high (e.g., 400 mg/kg) due to its low potency. It is thus possible that sodium benzoate-mediated blockade of D-NNA inversion might be due to its nonspecific (or non-DAO-related) effects. In addition, after D-NNA was incubated with the pure enzyme of DAO in vitro without tissue homogenates, L-NNA was not produced, even though D-NNA was disposed. We propose that this occurred because D-NNA was first converted to its corresponding alpha-keto acid by DAO and then to L-NNA by transaminase(s); however, there was no direct evidence for this process. The goal of this study is to further elucidate the process of D-NNA chiral inversion both in vivo and in in vitro tissue homogenates by comparing mutant ddY/DAO(-/-) mice that lack DAO activity entirely compared to normal ddY/DAO(+/+) mice and Swiss mice. Furthermore, the ability to produce L-NNA from D-NNA-corresponding alpha-keto acids (N(G)-nitroguanidino-2-oxopentanoic acid) produced by porcine kidney-derived DAO (pkDAO) was also studied in the DAO inhibitor-pretreated rats. We found that D-NNA chiral inversion occurred in Swiss mice and ddY/DAO(+/+) mice both in vivo and in in vitro kidney homogenates, but not in ddY/DAO(-/-) mice, correlated to their DAO activities. The alpha-keto acid (N(G)-nitro-guanidino-2-oxopentanoic acid) from D-NNA was able to produce L-NNA, and subsequent vasoconstriction and pressor responses. These results indicate that the role of renal DAO is indispensible but insufficient for chiral inversion of D-NNA and other neutral and polar D-amino acids, and unidentified aminotransferase(s) are involved in a subsequent mechanism for the process of chiral inversion. |
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Authors:
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Yan-Fei Xin; Xin Li; Bin Hao; Nian Gong; Wen-Qiang Sun; Ryuichi Konno; Yong-Xiang Wang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemistry & biodiversity Volume: 7 ISSN: 1612-1880 ISO Abbreviation: Chem. Biodivers. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-30 Completed Date: 2010-10-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101197449 Medline TA: Chem Biodivers Country: Switzerland |
Other Details:
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Languages: eng Pagination: 1413-23 Citation Subset: IM |
Affiliation:
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King's Lab, School of Pharmacy, Shanghai Jiao Tong University, No. 6 Biomedicine Building (Suite 106), 800 Dongchuan Road, Shanghai 200240, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals D-Amino-Acid Oxidase / antagonists & inhibitors, genetics, metabolism* Keto Acids / metabolism Kidney / enzymology Liver / enzymology Male Mice Nitroarginine / chemistry, metabolism* Rats Rats, Sprague-Dawley Sodium Benzoate / pharmacology Stereoisomerism Swine |
| Chemical | |
Reg. No./Substance:
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0/Keto Acids; 2149-70-4/Nitroarginine; 532-32-1/Sodium Benzoate; EC 1.4.3.3/D-Amino-Acid Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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