aldehyde oxidase Chemische Eigenschaften,Einsatz,Produktion Methoden
Biologische Funktion
In addition to metabolizing some aldehydes, aldehyde oxidase also oxidizes a variety of azaheterocycles but not thia- or oxaheterocycles.
Of the various purine nucleosides metabolized by aldehyde oxidase, the 2-hydroxy- and 2-amino derivatives are more efficiently
metabolized, and for the N9
-substituents, the typical order of preference is the acyclic nucleosides is as follows: 9-[(hydroxyalkyloxy)methyl]-purines) > 2′-deoxyribofuranosyl > ribofuranosyl > arabinofuranosyl > H. The kinetic rate constants for purine analogues
revealed that the pyrimidine portion of the purine ring system is more important for substrate affinity than the imidazole portion. Aldehyde
oxidase is inhibited by potassium cyanide and menadione (synthetic vitamin K).
Stoffwechsel
Aldehyde oxidase metabolizes an assortment of azaheterocycles including the short-acting sedative-hypnotic drug zaleplon (a
pyrazolo[1,5α] pyrimidine derivative) to its 5-oxo metabolite; the anticancer drug thioguanine to 8-oxothioguanine; the α2-adrenergic
agonist brimonidine (a pyrimidine derivative) to its 2-oxo-, 3-oxo-, and 2,3-dioxo- metabolites; quinine and quinidine to their 2-quinolone
metabolites; the pro-antiviral drug famiclovir (a purine derivative) to its active 6-oxo metabolite (penciclovir); O6
-benzylguanine to its 8-oxo
metabolite (also formed primarily from CYP3A4); the metabolism of the anticancer drug DACA (an acridine-4-carboxamide derivative) to its
9-acridone metabolite; and the antiseizure drug zonisamide (a 1,2-benzisoxazole derivative) primarily by reductive cleavage of the
1,2-benzisoxazole ring to 2-sulfamoylacetylphenol. Although the azaheterocycles thiazole and oxazole are not metabolized by aldehyde
oxidase, their carbocyclic analogues, benzothiazole, benzoxazole, and 1,2-benzisoxazole, are metabolized. On the other hand, the
heterocycles, benzothiophene and benzofuran, which do not contain a nitrogen atom, are not metabolized by or inhibit aldehyde oxidase.
The hepatotoxic and neurotoxic 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) is metabolized by aldehyde oxidase to its nontoxic
MP-2-pyridone metabolite (MPTP lactam). Although S-cotinine is formed primarily from S-nicotine in human smokers by CYP2A6, in vitro
studies suggest that aldehyde oxidase contributes to S-nicotine metabolism by oxidizing the intermediate metabolite (S-nicotine ?-1′,5′
-imminium ion) to S-cotinine. These results suggest that hepatic aldehyde oxidase is a key detoxification enzyme for MPTP and S-nicotine.
aldehyde oxidase Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
