Conversion of Hydroxyproline to Pyrrole-2-Carboxylic Acid

Although studies on the degradative metabolism of hydroxyproline have revealed that this amino acid is converted at least in part to glutamic acid (I-G), knowledge of the intermediates in this conversion and of other products of hydroxyproline metabolism is not yet complete. In the course of experiments on the metabolism of hydroxyproline, it was observed that incubation of hydroxyproline with kidney pre.parations led to the formation of a compound which we have identified as pyrrole-2-carboxylic acid (PCA) (7).’ Subsequent study revealed that kidney D-amino acid oxidase oxidizes hydroxy-n-proline and allohydroxy-n-proline to an intermediate compound which appears to be Al-pyrroline-4-hydroxy-2-carboxylic acid. The int’ermediate is spontaneously converted (at pH 8.3) to PCA; this conversion occurs much more rapidly in acid solution. PCA formation was also observed as a product of t,ransamination of y-hydroxyornithine with glyoxylate, pyruvate, or wketoglutarate. The evidence suggests that such transamination, in contrast to that of ornithine (8, 9), involves the a-amino group rather than the b-amino group. This report describes experiments on the formation of PCA by enzymatic oxidation, by enzymatic and non-enzymatic transamination, and also by non-enzymatic oxidation of hydroxyproline by hydrogen peroxide. Some implications of these findings in terms of the metabolism of hydroxyproline are discussed.