Anthranilate 2,3-hydroxylase

Subramanian V, CS Vaidyanathan (1984) Anthranilate hydroxylase from Aspergillus niger new type of NADPH-linked nonheme iron monooxygenase. J Bacteriol 160 651-655. 

Flavoprotelns introducing oxygen at site adjacent to existing hydroxy group 4-hydroxybenzoate hydroxylase Anthranilate hydroxylase in yeasts Salicylate hydroxylase... 

Powlowski J, S Dagley, V Massey, DP Ballou (1987) Properties of anthranilate hydroxylase (deaminating), a flavoprotein from Trichosporon cutaneum. J Biol Chem 262 69-74. 

An enzymatic pathway for indole degradation was found in A. niger, inducible by the substrate within a 5-h period during growth. Among the enzymes found, anthranilate hydroxylase, N-formylanthranilate deformylase, 2,3-dihydroxybenzoate decarboxylase, and catechol dioxygenase were isolated, and their activities were demonstrated in a cell-free system [342],... 

This enzyme [EC 1.14.12.1], also known as anthranilate hydroxylase, decarboxylating, catalyzes the reaction of anthranilate with NAD(P)H, dioxygen, and two water molecules to produce catechol, carbon dioxide, NAD(P)+, and ammonia. The enzyme requires an iron ion as a cofactor. 

ANTHOCYANIDIN SYNTHASE ANTHRANILATE 1,2-DIOXYGENASE ANTHRANILATE HYDROXYLASE... 

ACYL-CoA DEHYDROGENASES ADRENODOXIN ANTHRANILATE HYDROXYLASE AQUACOBALAMIN REDUCTASES... 

DHBA is also an intermediate in the catabolism of L-tryptophan. 2,3-DHBA is formed in this pathway from anthranilate, by the enzyme anthranilate hydroxylase through deamination [89]. 

Kobayashi, S., S. Kuno, N. Itada, O. Hayaishi, S. Kozuka, and S. Oae O Studies on Anthranilate Hydroxylases. A Novel Mechanism of Double Hydroxylation. Biochem. Biophys. Res. Commun. 16, 556 (1964). 

Kumar, R. P., N. S. Sreeleela, P. V. Subba Rao, and C. S. Vaidyanathan Anthranilate Hydroxylase from Aspergillus niger Evidence for the Partidpation of Iron in the Double Hydroxylation Reaction. J. Bacteriol. 113, 1213 (1973). 

The hepatic effects of cinnamyl anthranilate were evaluated in male CD 1 mice and male Fischer 344 rats treated by intraperitoneal injection for three consecutive days (Viswalingam Caldwell, 1997). At doses of 100 and 1000 mg/kg bw per day, relative liver weights of mice increased by 22% and 50%, respectively, 24 h after the final dose and peroxisomal (cyanide-insensitive) palmitoyl-coenzyme A (CoA) oxidation activity increased fivefold at both levels. Microsomal lauric acid 11- and 12-hydroxylase activity (CYP4A) was increased 15-fold at 100 mg/kg bw per day and 17-fold at 1000 mg/kg bw per day. Limited evaluation indicated that cirmamyl anthmilate increased the size and number of peroxisomes in electron micrographs of hepatocytes of treated mice. In rats, relative liver weights and peroxisomal palmitoyl-CoA oxidation activity were significantly increased only at 1000 mg/kg bw per day (22% and twofold, respectively). 

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. ... 

Related flavin hydroxylases act at nucleophilic positions on a variety of molecules393,402 including phenol,403 salicylate,404 anthranilate,405 p-c resol,406 4-hydroxyphenylacetate,407,408 and 4-aminobenzoate.409 Various microsomal flavin hydroxylases are also known 410 Flavin peroxide intermediates are also able to hydroxy late some electrophiles.411 For example, the bacterial cyclohexanone oxygenase catalyzes... 

Fig. 3. Biosynthesis of TIAs in C. roseus. Solid arrows indicate single enzymatic conversions, whereas dashed arrows indicate multiple enzymatic conversions. AS Anthranilate synthase, DXS D-l-deoxyxylulose 5-phosphate synthase G10H geraniol 10-hydroxylase CPR cytochrome P450 reductase TDC tryptophan decarboxylase STR strictosidine synthase SGD strictosidine /1-D-glucosidase D4H desacetoxyvindoline 4-hydroxylase DAT acetyl-CoA 4-O-deacetylvindoline 4-O-acetyl transferase. Genes regulated by ORCA3 are underlined. Reprinted with permission from [91]. Copyright (2000) American Association for the Advancement of Science...

Kynurenine Hydroxylase Kynurenine hydroxylase is an FAD-dependent mixed-function oxidase of the outer mitochondrial membrane, which uses NADPH as the reductant. The activity of kynurenine hydroxylase in the liver of riboflavin-deficient rats is only 30% to 50% of that in control animals, and deficient rats excrete abnormally large amounts of kynurenic and anthranilic acids after the administration of a loading dose of tryptophan, and, correspondingly lower amounts of quinolinate and niacin metabolites. Riboflavin deficiency may thus be a contributory factor in the etiology of pellagra when intakes of tryptophan and niacin are marginal (Section 8.5.1). 

Fig. 10. In vitro activities of the enzymes of alkaloid biosynthesis and rates of alkaloid formation in hyphae of Penicitlium cyclopium (75). Cultivation conditions were as described in the legend to Fig. 9. At the times indicated by arrows, cycloheximide (100 p.g/ml) was added to the culture medium. All values are in units per 1 cm of culture area. (A) Anthranilate adenylyltransferase (AA) (100 = 5.6 pkat) ( ) cyclopeptine dehydrogenase (CD) (100 = 40 pkat) ( ) dehydrocyclopeptine epoxidase (DE) (100 = 0.42 pkat) (A) cyclopenin m-hydroxylase (CH) (100 = 12 pkat) (O) cyclopenin-cyclopenol formation in vivo (100 = 9 pmol/sec).

The third kind of hydroxylase activity is the only one pertinent to the present review and refers to a mono-oxygenase of the hydroxylase type. This catalyses the insertion of a -OH group in place of a hydrogen atom at the 3-position of anthranilic acid, leading to HA. This evenience is often simply ignored by many authors dealing with tryptophan metabolism, so it could seem that the only possibility of HA formation is the action of kynureninase on HK. The actual occurrence of a true hydroxylase, as defined above, could however be considered debatable for a number of reasons, but some authors merely notice the activity without giving any reference to it. 

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