3-Hydroxy-anthranilic acid

Anthramycin is a benzodiazepine alkaloid with potent antitumor and antibiotic activity produced by the thermophilic actinomycete Streptomyces refuineus sbsp. thermotolerans. Using a genome-scanning approach, the biosynthesis was found to involve condensation of 4 methyl-3-hydroxy anthranilic acid 136 and a... 

This observation is related to that made by us (P4a) that kynurenine alone, or sometimes together with 3-hydroxykynurenine and 3-hydroxy-anthranilic acid, was found to be abnormally elevated in 17 of cases with renal tumors, in 3 of 6 cases with pelvic tumors, and in 1 of 2 cases with cystic renal disease. 

Various reports in the literature indicate the influence of endocrine organs on tryptophan metabolism. Chiancone and co-workers (C5, V2) reported that ovariectomy or hypophysectomy of rats caused increased excretion of xanthurenic acid and that adrenalectomy caused a decrease. An adrenal mechanism is suggested for the regulation of 3-hydroxy-anthranilic acid conversion to nicotinic and picolinic acids (M7). 

A leukemogenic efFect of 3-hydroxyanthranilic acid was observed in RFH strain mice 132 days after 40 subcutaneous doses of 5 mg 3-hydroxy-anthranilic acid (El). 

K18. Kotake, Y., and Nogami, K., Xanthurenic acid. XIII. EfiFect of 5-hydroxy-anthranilic acid on the formation and conjugating reaction of xanthurenic acid in albino rat. ]. Biochem. (Tokyo) 43, 437-443 (1956). 

Hydroxy anthranilic Acid (5-OH-AA). This was synthesized from m-hydroxybenzoic acid by coupling with diazotized rosaniline and subsequent reduction with sodium dithionite. The recrystallized product had a melting point of 242°C. (dec.). 

Under suitable Conditions, the protoplasts from Streptomyces anti-bioticus readily incorporated radioactively-labelled threonine, valine, proline, glycine and methionine into the relevant positions of actinomycins. Administration of radioactive tryptophan yielded actinomycins labelled in the chromophore. When the oxygen pressure was low, trace amounts of 4-methyl-3-hydroxy-anthranilic acid, which is an intermediate in the biosynthesis of the chromophoric part of actinomycin, could be detected. 

D 8.4.1 3-Hydroxy anthranilic Acid Derivatives and Phenoxazines Chemistry... 

S-Hydroxyanthranilic Oxidase. In animals an oxidation of 3-hydroxy-anthranilic acid by an oxidase from liver is known, but it is not known that other reactions do not occur. The oxidase, a soluble enzyme that survives acetone drying, consumes one equivalent of O2 in forming an unstable product believed to have the structure shown in (XI).This... 

Nicotinic Add Metabolism. The sequence of reactions leading to the formation of pyridine compounds is of particular interest as a source of nicotinic acid. Nutritional, isotopic, and genetic experiments have all shown that tryptophan and its metabolic derivatives including 3-hydroxy-anthranilic acid are precursors of nicotinic acid in animals and in Neuro-spora. The terminal steps in this sequence are not known. Under certain physiological conditions an increase in picolinic carboxylase appears to reduce nicotinic acid synthesis. This implies a common pathway as far as the oxidation of 3-hydroxyanthranilic acid. Whether quinolinic acid is a precursor of nicotinic acid is still uncertain. The enzyme that forms the amide of nicotinic acid also has not been isolated. Subsequent reactions of nicotinamide include the formation of the riboside with nucleoside phosphorylase and methylation by nicotinamide methyl-kinase. In animals W-methylnicotinamide is oxidized to the corresponding 6-pyridone by a liver flavoprotein. Nicotinic acid also forms glycine and ornithine conjugates. Both aerobic and anaerobic bacteria have been found to oxidize nicotinic acid in the 6-position. ... 

Bonner, D. M. and Yanofsky, C. (1949) Quinolinic acid accumulation in the conversion of 3-hydroxy-anthranilic acid to niacin in Neurospora. Proc. Nat. Acad. Sci. 35, 576-581. 

Y Nishizuka, O Hayaishi. Enzymic synthesis of niacin nucleotides from 3-hydroxy-anthranilic acid in mammalian liver. J Biol Chem 238 PC483-485, 1963. 

Morgan, L. R., D. M. Weimorts, and C. C. Aubert Oxidation of 3-hydroxy-anthranilic acid by soluble liver fraction from poikilothermic vertebrates. Biochim. et Biophys. Acta 100, 393 (1965). 

Weissbach, H., B. Redfield, V. Beavan, and E. Katz 4-Methyl-3-hydroxy-anthranilic acid, an intermediate in actinomycin biosynthesis. Biochem. Biophys. Research Commun. 19, 524 (1965). 

The aminoacid tryptophan is degraded by the higher plants to indole-3-acetic acid which is an important growth hormone for them, whereas bacteria usually degrade it to tryptamine, and mammals to 3-hydroxy-anthranilic acid and thence to nicotinic acid which is an indispensable metabolite. 

---