Nitro analogs of substrates for argininosuccinate synthetase and argininosuccinate lyase.
Arch Biochem Biophys
; 232(2): 520-5, 1984 Aug 01.
Article
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| MEDLINE
| ID: mdl-6547814
The nitro analogs of aspartate and argininosuccinate were synthesized and tested as substrates and inhibitors of argininosuccinate synthetase and argininosuccinate lyase, respectively. The Vmax for 3-nitro-2-aminopropionic acid was found to be 60% of the maximal rate of aspartate utilization in the reaction catalyzed by argininosuccinate synthetase. Only the nitronate form of this substrate, in which the C-3 hydrogen is ionized, was substrate active, indicating a requirement for a negatively charged group at the beta carbon. The V/K of the nitro analog of aspartate was 85% of the value of aspartate after correcting for the percentage of the active nitronate species. The nitro analog of argininosuccinate, N3-(L-1-carboxy-2-nitroethyl)-L-arginine, was a strong competitive inhibitor of argininosuccinate lyase but was not a substrate. The pH dependence of the observed pKi was consistent with the ionized carbon acid (pK = 8.2) in the nitronate configuration as the inhibitory material. The pH-independent pKi of 2.7 microM is 20 times smaller than the Km of argininosuccinate at pH 7.5. These results suggest that the tighter binding of the nitro analog relative to the substrate is due to the similarity in structure to a carbanionic intermediate in the reaction pathway.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arginina
/
Argininosuccinatoliasa
/
Argininosuccinato Sintasa
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Ácido Argininosuccínico
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Alanina
/
Ligasas
/
Liasas
Idioma:
En
Revista:
Arch Biochem Biophys
Año:
1984
Tipo del documento:
Article
Pais de publicación:
Estados Unidos