Enzymatic hydroxylation of aromatic compounds

Mitoma, Chozo; Posner, Herbert S.; Reitz, H. C.; Udenfriend, Sidney

doi:10.1016/0003-9861(56)90366-6

Cited by 270 publications

(47 citation statements)

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“…The "hydroxylase" was similarly located in the liver microsomes and, although both reduced tri-and diphosphopyridine nucleotides (TPNH and DPNH) and oxygen were required for maximal activity, high activity was supported by TPNH and oxygen alone. The system differed from that of Mitoma et al (1956) however in not being inhibited by the metal binding compounds a, a'-dipyridyl and o-phenanthroline.Further investigation of the naphthalene hydroxylating system by Booth andBoyland (1957, 1958) confirmed the findings of Mitoma et al with respect to the cellular distribution and requirements of the system but it was found …”

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confidence: 73%

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confidence: 73%

“…It was first shown by Mitoma, Posner, Reitz and Udenfriend (1956) that an enzyme system capable of hydroxylating a variety of organic compounds was able to effect the in vitro conversion of naphthalene into 1-naphthol (but not 2-naphthol) and a dihydrodiol-like compound which yielded 1-naphthol on acid hydrolysis. The system was located in the microsomal fraction of liver homogenate (but not of brain, kidney, lung and muscle) and required reduced triphosphopyridine nucleotide and oxygen for activity.…”

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confidence: 99%

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The Polycyclic Hydrocarbons: Metabolism, Cellular Binding and Carcinogenesis

Kh¹

1959

Br J Cancer

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THE data reported in the preceding communication (Harper, 1959) have led to the conclusion that the only important difference between the metabolisms of carcinogenic and non-carcinogenic hydrocarbons lies in the positions of the molecule at which hydroxylation initially occurs. Two possible explanations of this difference were considered to be:(a) That the reactive centres of carcinogenic hydrocarbons are initially blocked by cellular material; or (b) that different mechanisms of hydroxylation are operative during the metabolism of carcinogenic and non-carcinogenic hydrocarbons respectively. The mechanism of aromatic hydroxylation is a subject which has received much attention in recent years but so far the investigations have been confined to only two members of the polycyclic hydrocarbon series, namely, naphthalene and 3: 4-benzpyrene. Fortunately for the purpose of this discussion, however, these may be regarded as typical members of the non-carcinogenic and carcinogenic hydrocarbons respectively.It was first shown by Mitoma, Posner, Reitz and Udenfriend (1956) that an enzyme system capable of hydroxylating a variety of organic compounds was able to effect the in vitro conversion of naphthalene into 1-naphthol (but not 2-naphthol) and a dihydrodiol-like compound which yielded 1-naphthol on acid hydrolysis. The system was located in the microsomal fraction of liver homogenate (but not of brain, kidney, lung and muscle) and required reduced triphosphopyridine nucleotide and oxygen for activity.A similar enzyme system was found by Conny, Miller and Miller (1957) to effect the hydroxylation of 3: 4-benzpyrene and the products thus obtained were identical to those yielded during in vivo metabolism of the hydrocarbon. The "hydroxylase" was similarly located in the liver microsomes and, although both reduced tri-and diphosphopyridine nucleotides (TPNH and DPNH) and oxygen were required for maximal activity, high activity was supported by TPNH and oxygen alone. The system differed from that of Mitoma et al. (1956) however in not being inhibited by the metal binding compounds a, a'-dipyridyl and o-phenanthroline.Further investigation of the naphthalene hydroxylating system by Booth andBoyland (1957, 1958) confirmed the findings of Mitoma et al. with respect to the cellular distribution and requirements of the system but it was found

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The Polycyclic Hydrocarbons: Metabolism, Cellular Binding and Carcinogenesis

Kh¹

1959

Br J Cancer

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“…In experiments in vitro in which naphthalene is incubated with rabbit-or rat-liver microsomal fractions (Mitoma, Posner, Reitz & Udenfriend, 1956;Booth & Boyland, 1958) and with rat-liver slices (Booth, Boyland & Sims, unpublished observations), 1-naphthol or 1-naphthyl sulphate is detected but not the 2-isomers. In animals treated with naphthalene or with trans-1:2-dihydro-1:2-dihydroxynaphthalene, free 2-naphthol is present (usually in greater amounts than free 1-naphthol), but 2-naphthyl sulphate or glucosiduronate has not been detected.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of polycyclic compounds. 14. The conversion of naphthalene into compounds related to trans-1:2-dihydro-1:2-dihydroxynaphthalene by rabbits

Sims

1959

Biochemical Journal

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389 sequent chromatographic separations of the individual constituents. The partitioning of brain lipids between aqueous methanolic and chloroformrich phases, according to the method of Folch et al. (1957), resulted in the complete transfer of the strandin into the upper phase. In unpublished work, we have shown that negligible amounts of other lipids are lost in this way. However, the water-soluble non-lipid impurities do pass into the upper phase (cf. also Folch et al. 1957). The carbohydrate content is about 30 % greater than would be expected from the composition of strandin (Bogoch, 1958), and this excess probably represents water-soluble sugars and their derivatives.The presence of this extra carbohydrate in the upper phase almost certainly accounts for the extra peak at 440 m,u (Fig. 2), after the orcinol reaction. Although small in absolute amount, this carbohydrate would also contribute significantly to the absorption at 570 m,, so giving an erroneously high value for the neuraminic acid content based on direct readings of E570 . The use of 'difference' extinctions, depending on the selective destruction of neuraminic acid by hot-acid treatment, satisfactorily removes this interference. SUMMARY 1. Synthetic N-acetylneuraminic acid and partially purified ox-brain strandin have been subjected to Bial's orcinol reaction and the characteristics of the absorption spectra have been studied.2. Crude ox-brain lipids under similar conditions showed anomalous spectra, which were largely traced to the presence of cerebroside.3. Partitioning of ox-brain lipids between aqueous methanolic and chloroform-rich phases caused the strandin to pass completely into the upper aqueous methanolic phase. The neuraminic acid content of this phase was determined by measuring the 'difference' extinction at 570 mjL of the orcinol-reaction products (untreated minus acid-treated).4. Neuraminic acid has been determined in the lipids of several rat tissues. It was found only in the brain.

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“…The liver microsomes were prepared by the method of Mitoma et al [8]. FMO was purified from the porcine liver microsomes by the method of Wu and Ichikawa *Corresponding author.…”

Section: Preparation Of Liver Microsomes and Purification Of Fmomentioning

confidence: 99%

Inhibition of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine metabolic activity of porcine FAD‐containing monooxygenase by selective monoamine oxidase‐B inhibitors

Ichikawa

1995

FEBS Letters

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The MPTP metabolic activity of porcine FAD-containing monooxygenase (FMO) (EC 1.14.13.8) was inhibited considerably by deprenyl and pargyline, selective MAO-B inhibitors, and they showed typical competitive inhibition. Deprenyl and pargyline, amine derivatives were also examined as to whether they are substrates for the FMO. It was found that deprenyl and pargyline are excellent substrates for the FMO. The K i and K m values of deprenyl and pargyline for the FMO are 14 pM and 9 pM, and 14.3 pM and 11.6 pM, at pH 8.0 and 25°C, respectively.Key words." FAD-containing monooxygenase; Monoamine oxidase-B inhibitor; Deprenyl; Pargyline [6]. The optical spectra of FMO are shown in Fig. 1, and the purified FMO gave a single protein band on SDS-PAGE (Fig. 2). Enzyme assay and kinetic parametersThe enzymatic activity was determined optically and aerobically by measuring the decrease in absorbance at 340 nm due to the oxidation of NADPH in the presence of a substrate. The reaction mixture comprised FMO (0.2 nmol), 0.1 M K-phosphate buffer, pH 8.0, at 25°C, and appropriate amounts of NADPH and 10 ~M to 600 ¢tM substrate, in a final volume of 1 ml. The reaction mixture was put into a cuvette of 1 cm light path and then the endogenous rate of the absorbance change at 340 nm was recorded for 5 rain at 25°C before addition of the substrate. After the addition of the substrate, the rate of the absorbance change was measured for 5 rain at 25°C, the endogenous rate being subtracted. For investigation of a reaction with a sequential Bi Bi mechanism, the Km, Vmax and K~ values of FMO for deprenyl and pargyline can be determined by means of Lineweaver-Burk plots [9].

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Enzymatic hydroxylation of aromatic compounds

Cited by 270 publications

References 17 publications

The Polycyclic Hydrocarbons: Metabolism, Cellular Binding and Carcinogenesis

The Polycyclic Hydrocarbons: Metabolism, Cellular Binding and Carcinogenesis

Metabolism of polycyclic compounds. 14. The conversion of naphthalene into compounds related to trans-1:2-dihydro-1:2-dihydroxynaphthalene by rabbits

Inhibition of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine metabolic activity of porcine FAD‐containing monooxygenase by selective monoamine oxidase‐B inhibitors

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