Recoupling the cardiac nitric oxide synthases: tetrahydrobiopterin synthesis and recycling.
Curr Heart Fail Rep
; 9(3): 200-10, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22711313
ABSTRACT
Nitric oxide (NO), a key regulator of cardiovascular function, is synthesized from L-arginine and oxygen by the enzyme nitric oxide synthase (NOS). This reaction requires tetrahydrobiopterin (BH4) as a cofactor. BH4 is synthesized from guanosine triphosphate (GTP) by GTP cyclohydrolase I (GTPCH) and recycled from 7,8-dihydrobiopterin (BH2) by dihydrofolate reductase. Under conditions of low BH4 bioavailability relative to NOS or BH2, oxygen activation is "uncoupled" from L-arginine oxidation, and NOS produces superoxide (O (2) (-) ) instead of NO. NOS-derived superoxide reacts with NO to produce peroxynitrite (ONOO(-)), a highly reactive anion that rapidly oxidizes BH4 and propagates NOS uncoupling. BH4 depletion and NOS uncoupling contribute to overload-induced heart failure, hypertension, ischemia/reperfusion injury, and atrial fibrillation. L-arginine depletion, methylarginine accumulation, and S-glutathionylation of NOS also promote uncoupling. Recoupling NOS is a promising approach to treating myocardial and vascular dysfunction associated with heart failure.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biopterinas
/
Superóxidos
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Óxido Nítrico Sintase
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Óxido Nítrico
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article