The use of isotopic nitrogen in a study of the conversion of 3-hydroxyanthranilic acid to nicotinic acid in Neurospora

Abstract

Recent studies with mutant strains of Neurospora indicated that 3-hydroxyanthranilic acid (3-hydroxy-2-aminobenzoic acid) is an intermediate in the metabolic conversion of tryptophan to nicotinic acid. Evidence for this conversion in mammals is found in the report that 3-hydroxyanthranilic acid can maintain the growth of rats on a nicotinic acid-deficient diet and in the work of Albert, Scheer, and Deuel, who found an increased excretion of N-methylnicotinamide by rats fed this substance. The isotopic experiments of Heidelberger, Abraham, and Lepkovsky demonstrated that the carboxyl carbon of 3-hydroxyanthranilic acid is the precursor of the carboxyl carbon atom of nicotinic acid. To study the mechanism of the conversion of the benzene ring into a pyridine derivative, a mutant strain of Neurospora crassa C-86, requiring 3-hydroxyanthranilic acid or a precursor for growth, was grown in a medium which contained non-labeled synthetic 3-hydroxyanthranilic acid and Nls ammonium chloride as the only sources of nitrogen. Thus the absence of N16 in excess in nicotinic acid isolated from the mold would indicate that the amino group of 3-hydroxyanthranilic acid is the precursor of the pyridine nitrogen in nicotinic acid.

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