Benzene hydroxylase

This enzyme [EC 1.14.12.3], also known as benzene hydroxylase, catalyzes the NADH-linked reaction of benzene and dioxygen to produce ds-l,2-dihydrobenzene-... 

Because LCEC had its initial impact in neurochemical analysis, it is not, surprising that many of the early enzyme-linked electrochemical methods are of neurologically important enzymes. Many of the enzymes involved in catecholamine metabolism have been determined by electrochemical means. Phenylalanine hydroxylase activity has been determined by el trochemicaUy monitoring the conversion of tetrahydro-biopterin to dihydrobiopterin Another monooxygenase, tyrosine hydroxylase, has been determined by detecting the DOPA produced by the enzymatic reaction Formation of DOPA has also been monitored electrochemically to determine the activity of L-aromatic amino acid decarboxylase Other enzymes involved in catecholamine metabolism which have been determined electrochemically include dopamine-p-hydroxylase phenylethanolamine-N-methyltransferase and catechol-O-methyltransferase . Electrochemical detection of DOPA has also been used to determine the activity of y-glutamyltranspeptidase The cytochrome P-450 enzyme system has been studied by observing the conversion of benzene to phenol and subsequently to hydroquinone and catechol... 

The dioxygenase nature of these reactions was first demonstrated by Kobayashi et al.201 with anthranilate 1,2-dioxygenase (hydroxylase). They demonstrated by experiments with 180 that both atoms of oxygen in catechol are exclusively derived from molecular oxygen. Subsequently, the incorporation of two atoms of molecular oxygen into substrates was established by tracer experiments with benzene 1,2-dioxygenase204 and benzoate 1,2-dioxygenase206. ... 

Aromatic hydrocarbons are mainly hydroxylated to phenolic products. Complex (12) hydroxylated benzene in MeCN at 20 °C into phenol in ca. 55% yield, and no isotope effect was found for this reaction. Hydroxylation of toluene mainly occurs at the ring positions, with minor amounts of benzylic oxidation products. Hydroxylation of 4-deuterotoluene by (12) occurred with 70% retention and migration of deuterium in the formation of p-cresol. This high NIH shift value is in the same range as that found for liver microsome cytochrome P-450 hydroxylase, and suggests the transient formation of arene oxide intermediates. 

Mathematical models of benzene and phenol metabolism suggest that the inhibition by benzene of phenol metabolism, and by phenol on benzene metabolism, occurs through competition for a common reaction site, which can also bind catechol and hydroquinone (Schlosser et al. 1993). Flavonoids have been shown to inhibit phenol hydroxylase or increase phenol hydroxylase activity in a dose-dependent manner, dependent on the oxidation potential of the flavonoid (Hendrickson et al. 1994). 

Comish HH, Ryan RC. 1965. Metabolism of benzene in nonfasted, fasted, and aryl-hydroxylase inhibited rats. Toxicol Appl Pharmacol 7 767-771. 

Various conceptual DFT-based reactivity indices in association with some new parameters are successfully employed in the development of stronger QSAR/QSTR models [332]. Deeper correlations of the toxicity of different classes of organic compounds like chlorinated benzenes [333], polychlorinated biphenyls [312, 334—336], and benzidine [337] at DFT level of theory are reported. The toxicity of the polychlorinated biphenyls as well as benzidine is itrfluenced by its electron affinity and planarity. The interactions of the chlorinated benzo-derivatives and benzidine with other biomolecules like nucleic acid/base pairs or aryl hydrocarbon hydroxylase (AHH) receptors are primarily of charge-transfer type, which can be quantitatively assessed from Parr to Pearson formula [254] and can be given as... 

It appears that humans, because of the course of evolution, do not have the biochemical ability to synthesize the benzene ring. As a result, phenylalanine and tryptophan derivatives are essential in the human diet. Because tyrosine can be synthesized from phenylalanine in a reaction catalyzed by an enzyme known as phenylalanine hydroxylase, it is not essential in the diet as long as phenylalanine is present. 

Specific vitamin D studies include the following. Sklan et al. (1973) used TLC to separate vitamin D from cholesterol and in combination with GLC determined 25-hydroxyvitamin Dj in chicken plasma. Vieth et al. (1978) used TLC to separate tritiated products in biochemical studies on kidney 25-OH-D hydroxylases. Mass spectrometric methods used to measure Vitamin D3 and 25-OH-D3 often utilize TLC as a prepurification step (Dueland et al., 1981). Czuczy and Morava (1982) extracted vitamin D from milk and determined it using TLC on silica gel with the mobile-phase benzene-ethanol (75 1). The chromatograms were visualized with SbClj and the vitamin D level was determined fluoromet-rically at 550 nm. 

CHAllENCEl Biochemical oxidation of aromatic rings is catalyzed by a group of liver enzymes called aryl hydroxylases. Part of this chemical process is the conversion of toxic aromatic hydrocarbons such as benzene into water-soluble phenols, which can be easily excreted. However, the primary purpose of the enzyme is to enable the synthesis of biologically useful compounds, such as the amino acid tyrosine from its relative phenylalanine (below). 

It is of interest that Grover and Sims (1964) found that aromatic hydrocarbons and narcotics, which induce hydroxylase activity, have a depressant effect on glutathione iS-arjdtransferase. Hydroxylases have a practically unlimited supply of substrate while the conjugases require glutathione, which rapidly depletes the liver. Nevertheless a severe sulfur amino acid defidency be generated by administration of bromo-benzene and other hydrocarbons or derivatives w-hich are metabolized to proportionately large amounts of mercapturic acids. 

The sensitizer acts as a catalyst to the over-all reaction, as it is regenerated by reaction (16). Whether the photochemical oxidation proceeds with or without sensitizer, the triplet state will lower the energy of activation for subsequent reaction with oxygen. Kemula and Grabowska (1960) have described a method of studying the reactivity of aromatic molecules in their lowest triplet state. They irradiated the system benzene-oxygen within the forbidden band (A 2900-3600 A) and obtained phenol and o-benzoquinone. This is the simplest model hydroxylase. 

The metabolism of tryptophan has been of interest to investigators in many different fields of biochemistry and medicine. The biological transformations of this indole derivative are very complex and involve a series of enzymes, which cause i) changes of the side chain (transaminases, decarboxylases, etc.) ii) splitting of the indole nucleus from the side chain (tryptophanase) iii) changes in the pyrrole nucleus (tryptophan pyrrolase, kynureninase, etc.) iiii) changes in the benzene ring (hydroxylases, etc.). 

Optically active epoxides are useful chiral synthons in the phamaceutical synthesis of prostaglandins. Microbial epoxidation of olefinic compounds was first demonstrated by van der Linden [241]. Subsequently, May et al. [242] demonstrated the epoxidation of alkenes in addition to hydroxylation of alkanes by an m-hydroxylase system. Oxidation of alk-l-enes in the range C6-C12, a,(o-dienes from C6-C12, alkyl benzene, and allyl ettiers were demonstrated using an co-hydroxylase enzyme system from Pseudomonas oleovorans. i -Epoxy compounds in greater than 75% e.e. were produced by epoxidation re tions using the co-hydroxylase system [243,244]. The epoxidation system from Nocardia cor-allina is very versatile, has broad substrate specificity, and reacts with unfunctionalized aliphatic as well as aromatic olefins to produce i -epoxides [245,246]. 

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