Human arginase II: crystal structure and physiological role in male and female sexual arousal.
Biochemistry
; 42(28): 8445-51, 2003 Jul 22.
Article
en En
| MEDLINE
| ID: mdl-12859189
ABSTRACT
Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. The X-ray crystal structure of a fully active, truncated form of human arginase II complexed with a boronic acid transition state analogue inhibitor has been determined at 2.7 A resolution. This structure is consistent with the hydrolysis of l-arginine through a metal-activated hydroxide mechanism. Given that human arginase II appears to play a role in regulating l-arginine bioavailability to NO synthase in human penile corpus cavernosum smooth muscle, the inhibition of human arginase II is a potential new strategy for the treatment of erectile dysfunction [Kim, N. N., Cox, J. D., Baggio, R. F., Emig, F. A., Mistry, S., Harper, S. L., Speicher, D. W., Morris, S. M., Ash, D. E., Traish, A. M., and Christianson, D. W. (2001) Biochemistry 40, 2678-2688]. Since NO synthase is found in human clitoral corpus cavernosum and vagina, we hypothesized that human arginase II is similarly present in these tissues and functions to regulate l-arginine bioavailability to NO synthase. Accordingly, hemodynamic studies conducted with a boronic acid arginase inhibitor in vivo are summarized, suggesting that the extrahepatic arginase plays a role in both male and female sexual arousal. Therefore, arginase II is a potential target for the treatment of male and female sexual arousal disorders.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arginasa
/
Nivel de Alerta
/
Sexualidad
/
Hemodinámica
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Biochemistry
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos