Enzyme anthranilate hydroxylase

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]. 

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. 

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).

Kynurenine is hydroxylated to hydroxykynurenine by an enzyme (kynurenine-3-hydroxylase) found in rat liver mitochondria. The reaction requires NADPH and molecular oxygen. In the presence of pyridoxal phosphate, hydroxykynurenine is hydrolyzed by an enzyme (kynurenase) found in liver and kidney. The product of this reaction is 3-hydroxyanthranilic acid. The same enzyme catalyzes the cleavage of the side chain of kynurenine to yield alanine and anthranilic acid. Studies made with labeled 3-hydroxyanthranilic acid demonstrated its role as an intermediate of the biosynthesis of nicotinic acid. These studies established that the label of the carbon 3 of 3-hydroxyanthranilic acid is transferred to the a-carbon of quinolinic acid and is lost as C14O2 during the conversion of quinolinic to nicotinic acid. The details of the metabolic conversion of 3-hydroxyanthranilic acid to nicotinic acid are known. 

Phenylalanine hydroxylase occurs only in mammalian liver (that is, in the rat, guinea-pig, rabbit, d<, chicken, and human) (see also 259). No activity has been observed in (rat) lung, kidney, brain, or muscle. The system is quite speciOc for L-phenylalanine. Tjrro-sine is not formed from n-phenylalanine, nor are the corresponding p-phenols formed from N-acetyl- or N-chloroacetyl-L-phenylalanine, L-phenylalanine ethyl ester, DL-phenylglycine, phenylserine, phenylpyruvic acid, phenylethylamine, benzoic acid, hippuric acid, cinnamic acid, or mandelic acid (768), or from aniline, acetanilide, tryptophan, kynurenine, anthranilic acid, or phenylacetate (557). This specificity is a distinguishing character of the enzyme, which occurs in the same tissue as the nonspecific aromatic hydroxylase described above. 

In the course of the metabolic transformation of trsrptophan to 3-hydroxyanthranilic acid and xanthurenic acid (Fig. 4), 3-hydroxy-kynurenine is formed from kynurenine (182,538). An enzymic system which catalyzes this reaction has been observed in the livers of rats and cats (198). This 3-hydroxylase occms in mitochondria. It appears to be specific for L-kynurenine because n-kynurenine, A -acetyl-L-kynurenine, AT-acetyl-D-kynurenine, kynurenic acid, and anthranilic acid are not attacked. Only the 3-position of kynurenine is hydroxylated. 

---