Linked Life Data

9671515

Source:http://linkedlifedata.com/resource/pubmed/id/9671515

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
1998-8-5
pubmed:abstractText
A detailed comparison of the oxidation of five compounds closely related to L-arginine (Arg) by purified recombinant neuronal and macrophage NO synthases (NOS I and NOS II) was performed. Homo-L-arginine (homo-Arg) is oxidized by both NOSs in the presence of NADPH with major formation of NO and homo-L-citrulline, with a molar ratio of close to 1, and minor formation of N omega-hydroxyhomo-L-arginine (homo-NOHA). Oxidation of homo-NOHA by the two NOSs also leads to NO and homocitrulline in a 1:1 molar ratio. On the contrary, N omega-hydroxynor-L-arginine (nor-NOHA) is a very poor substrate of NOS I and II, which fails to produce significant amounts of nitrite. The catalytic efficiency of both NOSs markedly decreases in the order Arg > NOHA > homo-Arg > homo-NOHA, as shown by the 20- and 10-fold decrease of kcat/Km observed for NOS I and NOS II, respectively, when comparing Arg to homo-NOHA. The greater loss of catalytic efficiency for homo-Arg, when compared to that for Arg, appears to occur at the first step (N-hydroxylation) of the reaction. In that regard, it is noteworthy that the Vm values for NOHA and homo-NOHA oxidation are very similar (about 1 and 2 micromol of NO min-1 mg of protein-1 for NOS I and II, respectively). In fact, lengthening of the Arg chain by one CH2 leads not only to markedly decreased kcat/Km but also to clear disturbances in NOS functioning. This is shown by a greater accumulation of the N omega-hydroxyguanidine intermediate (homo-NOHA:homocitrulline ratio between 0.2 and 0.4) and an increased consumption of NADPH for NO formation (between 2.0 and 2.6 mol of NADPH consumed for the formation of 1 mol of NO in the case of homo-Arg, instead of 1.5 mol in the case of Arg). Most of the above results could be interpreted by comparing the possible positionings of the various substrates relative to the two NOS active oxygen species which are believed to be responsible for the two steps of the reaction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10453-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Substrate specificity of NO synthases: detailed comparison of L-arginine, homo-L-arginine, their N omega-hydroxy derivatives, and N omega-hydroxynor-L-arginine.
pubmed:affiliation
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université Paris V, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't