ENZYMATIC DECARBAMYLATION OF CARBAMYL β-ALANINE AND CARBAMYL β-AMINOISOBUTYRIC ACID

Abstract

The investigations of Fink et al. (l), which indicated a pathway for pyrimidine metabolism involving carbamyl amino acids, have been extended by Fink et al. (2,3) and others, the work of Canellakis (4) being particularly noteworthy in demonstrating the triphosphopyridine nucleotide requirement of rat liver preparations in the stepwise degradation of pyrimidines.In recent studies we have demonstrated (5, S), with partially purified preparations, the interconversion of pyrimidines and hydropyrimidines and of hydropyrimidines and carbamyl amino acids.The enzymes which catalyze these reactions, Reactions 1 and 2, have been purified from mammalian liver.We also reported previously (7) the existence of an enzyme in animal tissues able to decarbamylate carbamyl @alanine, Reaction 3. (1) Uracil g hydrouracil (2) Hydrouracil G carbamyl fl-alanine(3) Carbamyl @-alanine -+ CO% + NH3 + @-alanineRecently, similar reactions and the purification of the enzyme able to catalyze Reaction 1 have been reported in bacteria (8, 9).The bacterial enzyme which catalyzes Reaction 1 is, however, diphosphopyridine nucleotide-dependent (9) in contrast to the mammalian enzyme (4, 5).This paper presents some of the kinetic properties of a partially purified enzyme able to decarbamylate carbamyl @-alanine to fl-alanine, CO*, and NHa.The specificity and the lack of effect of metals on the enzyme indicate that it is not related to the "ureidosuccinase" of Lieberman and Kornberg (10) or to the "citrullinase" reaction (11,12).In addition, data on the distribution of the enzyme in several species and organs are included.Combination of Reactions 1, 2, and 3 provides a possible pathway for the production of /?-alanine in animal tissues (7, 13) and this is discussed further below in relation to the origin of carbamyl p-alanine in animal tissues (5-7, 13).