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Endogenous nitric oxide synthase inhibitors are responsible for the L ‐arginine paradox
Author(s) -
Tsikas Dimitrios,
Böger Rainer H,
Sandmann Jörg,
Bode-Böger Stefanie M,
Frölich Jürgen C
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01686-0
Subject(s) - arginine , nitric oxide , endogeny , nitric oxide synthase , asymmetric dimethylarginine , chemistry , biochemistry , enzyme , substrate (aquarium) , in vivo , atp synthase , biosynthesis , biology , amino acid , genetics , ecology , organic chemistry
L ‐Arginine, the substrate of nitric oxide (NO) synthases (NOSs), is found in the mammalian organism at concentrations by far exceeding K M values of these enzymes. Therefore, additional L ‐arginine should not enhance NO formation. In vivo, however, increasing L ‐arginine concentration in plasma has been shown repeatedly to increase NO production. This phenomenon has been named the L ‐arginine paradox; it has found no satisfactory explanation so far. In the present work, evidence for the hypothesis that the endogenous NOS inhibitors methylarginines, asymmetric dimethylarginine being the most powerful (IC 50 1.5 μM), are responsible for the L ‐arginine paradox is presented.