The dealkylation of some p-nitrophenylalkylethers and their α-deuterated analogues by rat liver microsomes

Al-Gailany, Kais A.S.; Bridges, James W.; Netter, K.J.

doi:10.1016/0006-2952(75)90156-2

Cited by 25 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 and 3 show that the Michaelis constants are lower than the dissociation constants of the 7-n-alkoxycoumarins. Likewise, Km is less than K. for the 0-dealkylation of p-nitrophenylalkyl ethers (Al-Gailany et al, 1975). These observations are compatible with the occurrence of additional intermediates in the reaction pathway after the formation of the enzyme-substrate complex.…”

Section: Discussionsupporting

confidence: 68%

“…For several homologous series of compounds, a good correlation has been found between the lipophilicity of the homologues and their interaction (binding, kinetic or inhibitory) with cytochrome P-450 (Cohen & Mannering, 1973;Al-Gailany et al, 1975Yih & Van Rossum, 1977; (S.D.) with r = 1.00.…”

Section: Discussionmentioning

confidence: 99%

“…For the latter compounds, however, side-chain hydroxylation has been observed which can compete for 0-dealkylation (Hunter & Wilson, 1981). In contrast, increasing metabolic rates with increasing alkyl-chain length have been observed for alcohols (Morgan et al, 1982) and p-nitrophenylalkyl ethers (Al-Gailany et al, 1975).…”

Section: Discussionmentioning

confidence: 99%

“…In this case, Km is always less than or equal to K, (Fersht, 1985). The involvement of hemiacetal intermediates has been suggested for the 0-dealkylation of aromatic ethers (Al-Gailany et al, 1975;Hunter & Wilson, 1981).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Interaction of 7-n-alkoxycoumarins with cytochrome P-4502 and their partitioning into liposomal membranes. Assessment of methods for determination of membrane partition coefficients

Vermeir

Boens

Heirwegh

1992

Biochemical Journal

View full text Add to dashboard Cite

A study was made of the binding of 7-ethoxy-, 7-n-propoxy-and 7-n-pentoxy-coumarin to cytochrome P-4502 reconstituted into large unilamellar liposomes composed of a mixture of egg L-a-phosphatidylcholine, egg phosphatidylethanolamine and dipalmitoyl phosphatidic acid (2:1:0.06, by weight). The apparent spectral dissociation constants QPP-increased linearly with increasing proteoliposomal concentration. When both cytochrome P-4502 and NADPH:cytochrome P-450 reductase were reconstituted into liposomes, the apparent Michaelis constants KmPP for 0-dealkylation of 7-methoxy-, 7-ethoxy-and 7-n-propoxy-coumarin showed a similar dependence on the proteoliposomal concentration. The results were in accordance with models for kinetic or equilibrium processes in biphasic systems containing membrane-bound catalytic or acceptor sites, in which a linear solute partition in the bilayer membrane is postulated. The methyl, ethyl and n-propyl ether were readily dealkylated. However, the O-dealkylation rate of 7-nbutoxycoumarin was low and became very small for longer alkyl ethers. Both the effective dissociation constants and effective Michaelis constants decreased with elongation of the alkyl side chain of the coumarins. From plots of the apparent dissociation constants and apparent Michaelis constants against the lipid volume fraction of the proteoliposomes, the membrane partition coefficients for several homologues were calculated. When protein-free liposomes were added to 7-n-alkoxycoumarin solutions, the fluorescence intensity of the coumarins decreased and eventually became negligible in the presence of an excess of liposomal material. On the assumption that the overall fluorescence can be ascribed exclusively to the fraction of 7-n-alkoxycoumarin molecules present in the aqueous phase, partition coefficients for liposomal accumulation of the test compounds could be determined directly. For several coumarin ethers, comparable values were derived for the membrane partition coefficients from binding, kinetic and fluorescence intensity measurements. The change in free energy per methylene group of the 7-n-alkoxycoumarins for partitioning between n-octanol and buffer was significantly different from the value for liposome partitioning.

show abstract

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Interaction of 7-n-alkoxycoumarins with cytochrome P-4502 and their partitioning into liposomal membranes. Assessment of methods for determination of membrane partition coefficients

Vermeir

Boens

Heirwegh

1992

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…O mecanismo da reação de O-desalquilação catalisada pelo citocromo P450 tem sido menos estudado do que o mecanismo de N-desalquilação [Weissman e Zewge, 2005;Al-Gailany et al, 1975;. Acredita-se que a oxidação ocorre sobre o carbono alfa, por abstração de hidrogênio (reação a, Figura 88), seguido por hidroxilação (reação b, Figura 88), que é o mecanismo bem conhecido de recombinação de oxigênio, "oxygen rebound" ].…”

Section: Iv3a6 -Oxidação Da Cbz Na Presença Do Catalisador De Jacounclassified

Metaloporfirinas e compostos salen como modelos biomiméticos do citocromo P450 no metabolismo de fármacos anticonvulsivante e antidepressivo

Leod¹,

Oliveira²

View full text Add to dashboard Cite

A selected bibliography of biomedical and environmental applications of stable isotopes. I—Deuterium 1971-1976

Klein

1978

Biol. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

The dealkylation of some p-nitrophenylalkylethers and their α-deuterated analogues by rat liver microsomes

Cited by 25 publications

References 10 publications

Interaction of 7-n-alkoxycoumarins with cytochrome P-4502 and their partitioning into liposomal membranes. Assessment of methods for determination of membrane partition coefficients

Interaction of 7-n-alkoxycoumarins with cytochrome P-4502 and their partitioning into liposomal membranes. Assessment of methods for determination of membrane partition coefficients

Metaloporfirinas e compostos salen como modelos biomiméticos do citocromo P450 no metabolismo de fármacos anticonvulsivante e antidepressivo

A selected bibliography of biomedical and environmental applications of stable isotopes. I—Deuterium 1971-1976

Contact Info

Product

Resources

About