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Inactivation of neuronal nitric oxid...
~
Demady, Damon Russell.
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Inactivation of neuronal nitric oxide synthase.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Inactivation of neuronal nitric oxide synthase./
作者:
Demady, Damon Russell.
面頁冊數:
112 p.
附註:
Chair: Yoichi Osawa.
Contained By:
Dissertation Abstracts International62-06B.
標題:
Chemistry, Biochemistry. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3016832
ISBN:
0493278338
Inactivation of neuronal nitric oxide synthase.
Demady, Damon Russell.
Inactivation of neuronal nitric oxide synthase.
- 112 p.
Chair: Yoichi Osawa.
Thesis (Ph.D.)--University of Michigan, 2001.
This thesis helps to explain how nNOS inactivators act mechanistically and will contribute to our understanding of how NOS inactivation contributes to xenobiotic-mediated toxicity and pathology of certain disease states.
ISBN: 0493278338Subjects--Topical Terms:
1017722
Chemistry, Biochemistry.
Inactivation of neuronal nitric oxide synthase.
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Nitric oxide (NO) is a major biological second messenger. NO is involved in homeostatic regulation as well as several pathophysiological conditions. NO is synthesized by the nitric oxide synthase family of enzymes (NOS) by converting L-arginine to L-citrulline and NO. Because of the difficulty in controlling NO once it has been synthesized and released, there has been a focus on modulating its synthesis by inhibiting the NOS isoforms. NOS inactivators have been important in understanding the NOS catalytic mechanism and serve as therapeutic agents for the control of NO synthesis. This thesis work focuses on identifying novel neuronal NOS (nNOS) inactivators and characterizing them kinetically and mechanistically.
520
$a
We established a microtiterplate spectral assay to distinguish between the various classes of NOS inhibitors. We investigated whether several antihypertensive drugs with a guanidine moiety, which are structurally similar to the natural substrate L-arginine, cause nNOS inactivation. We found that two of these drugs, debrisoquin and guanethidine were time-dependent nNOS inhibitors, and so this gradual inhibitory effect on nNOS should be considered when assessing the long-term effects on patients using these drugs.
520
$a
We discovered that agmatine, an endogenously produced polyamine, is a mechanism-based inactivator of nNOS. Agmatine caused the destruction and alteration of the heme prosthetic group of nNOS, leading to the inactivation of the enzyme. The mechanism for the inactivation is by production of hydrogen peroxide secondary to an increase in the nNOS oxidase activity.
520
$a
Because of recent evidence of NOS deficiency in smokers, we investigated whether chemicals found in tobacco could inactivate nNOS. We showed that there was at least one polar, hydrophilic component in tobacco that inactivated nNOS <italic>in vitro</italic>. This is the first study to demonstrate nNOS inactivation <italic>in vitro</italic> by constituent(s) of tobacco and suggests that cigarette-mediated inactivation of nNOS should be considered in the long and short-term physiological consequences of smoking.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3016832
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