Spelling suggestions: "subject:"heterocyclic cation"" "subject:"nheterocyclic cation""
1 |
Specificity of aldehyde oxidase towards N-heterocyclic cations : oxidation of quinolinium and related cations by aldehyde oxidase in vitro : the isolation of two products formed simultaneously from a single substrateTaylor, Susan Mary January 1984 (has links)
Aldehyde oxidase catalysed oxidation of various quinolinium and related cations has been studied in vitro. Oxidation products were identified by comparison of their spectral and chromatographic characteristics with those of authentic compounds. The N-heterocyclic cations and quinolones used required synthesis. Incubation of N-methylquinolinium, N-methyl-7,8-benzoquinolinium and N-phenylquinolinium yielded the corresponding 2- and 4-quinolones simultaneously. The ratio of 2- to 4-quinolone formation was found to be species dependent; the proportion of 4-quinolone was greater with guinea pig enzyme than with rabbit enzyme. Incubation of N-methyl-4-methylquinolinium, N-methyl-4-phenylquinolinium and N-methylphenanthridinium produced the expected 2-quinolones. Cations substituted adjacent to the ring nitrogen, i. e. N-methyl-2- methylquinolinium, N-methyl-2-phenylquinolinium and N-phenyl-2-phenylquinolinium, were oxidised to the corresponding 4-quinolones. Kinetic constants were determined spectrophotometrically. The Km values obtained with rabbit enzyme ranged from 1.6 x 10-3 M for N-methylquinolinium to <10-5 M for N-phenyl-2-phenylquinolinium. Quaternary compounds were found to be better substrates than their non-quaternary counterparts, except for N-methylisoquinolinium and N-methylphenanthridinium. In general, guinea pig aldehyde oxidase was shown to have a greater affinity for N-heterocyclic cations than rabbit enzyme. The substrate binding site has been discussed in the light of the results outlined below. Oxidation of N-methyl-4-phenylquinolinium (to the 2-quinolone) was competitively inhibited by N-methyl-2-phenylquinolinium (which yields the 4-quinolone), indicating that both these cations interact at the same active site. The ratio of 2- to 4-quinolone production from N-methylquinolinium was constant under various conditions, including purification of the enzyme but changed at high pH or in the presence of N-methylphenanthridinium. Inhibition studies indicated that both quaternary and non-quaternary compounds act at the same site on the enzyme. Km and Vmax values for phthalazine, N-methyl-2-phenylquinolinium and N-methylquinolinium were determined over the pH range 5.4 to 10.2. In each case, results indicated that the enzyme has an ionisable group at the active site with a pK ca. 8. Aldehyde oxidase was shown to catalyse the dehydrogenation of the pseudobases 3,4-dihydro-4-hydroxy-3-methyl-2-quinazolinone and 3,4-dihydro- 4-hydroxy-3-methylquinazoline.
|
2 |
Specificity of aldehyde oxidase towards N-heterocyclic cations. Oxidation of quinolinium and related cations by aldehyde oxidase in vitro; the isolation of two products formed simultaneously from a single substrate.Taylor, Susan M. January 1984 (has links)
Aldehyde oxidase catalysed oxidation of various quinolinium and
related cations has been studied in vitro. Oxidation products were
identified by comparison of their spectral and chromatographic
characteristics with those of authentic compounds. The N-heterocyclic
cations and quinolones used required synthesis.
Incubation of N-methylquinolinium, N-methyl-7,8-benzoquinolinium
and N-phenylquinolinium yielded the corresponding 2- and 4-quinolones
simultaneously. The ratio of 2- to 4-quinolone formation was found to
be species dependent; the proportion of 4-quinolone was greater with
guinea pig enzyme than with rabbit enzyme.
Incubation of N-methyl-4-methylquinolinium, N-methyl-4-phenylquinolinium
and N-methylphenanthridinium produced the expected 2-quinolones.
Cations substituted adjacent to the ring nitrogen, i. e. N-methyl-2-
methylquinolinium, N-methyl-2-phenylquinolinium and N-phenyl-2-phenylquinolinium,
were oxidised to the corresponding 4-quinolones.
Kinetic constants were determined spectrophotometrically. The Km
values obtained with rabbit enzyme ranged from 1.6 x 10-3 M for N-methylquinolinium
to <10-5 M for N-phenyl-2-phenylquinolinium. Quaternary
compounds were found to be better substrates than their non-quaternary
counterparts, except for N-methylisoquinolinium and N-methylphenanthridinium.
In general, guinea pig aldehyde oxidase was shown to have a greater affinity
for N-heterocyclic cations than rabbit enzyme.
The substrate binding site has been discussed in the light of the
results outlined below.
Oxidation of N-methyl-4-phenylquinolinium (to the 2-quinolone) was
competitively inhibited by N-methyl-2-phenylquinolinium (which yields the
4-quinolone), indicating that both these cations interact at the same
active site. The ratio of 2- to 4-quinolone production from N-methylquinolinium
was constant under various conditions, including purification
of the enzyme but changed at high pH or in the presence of N-methylphenanthridinium.
Inhibition studies indicated that both quaternary and non-quaternary
compounds act at the same site on the enzyme. Km and Vmax values for
phthalazine, N-methyl-2-phenylquinolinium and N-methylquinolinium were
determined over the pH range 5.4 to 10.2. In each case, results indicated
that the enzyme has an ionisable group at the active site with a pK ca. 8.
Aldehyde oxidase was shown to catalyse the dehydrogenation of the
pseudobases 3,4-dihydro-4-hydroxy-3-methyl-2-quinazolinone and 3,4-dihydro-
4-hydroxy-3-methylquinazoline.
|
Page generated in 0.1084 seconds