Beta-alanine Synthase

Thomas Traut

Research Interests

Dissociating Enzymes

UMP Synthase

Uridine Kinase

Beta-alanine Synthase

Purine & Pyrimidine Concentrations

Beta-alanine synthase (N-carbamoyl-beta-alanine amidohydrolase, EC; also called beta-ureidopropionase) is the only enzyme catalyzing the biosynthesis of beta-alanine in animals. It represents the third and final step in the catabolism of the pyrimidine bases uracil or thymine to produce beta-alanine or 2-methyl-beta-alanine. Beta-alanine synthase will use as substrate either N-carbamoyl-beta-alanine, derived from uracil, or (2-methyl)-N-carbamoyl-beta-alanine, from thymine. The figure below shows the opened pyrimidine ring, with standard numbering for the closed pyrimidine ring. Thymidine is 4-methyl-uridine.

Our studies have demonstrated that this is an allosteric enzyme with positive cooperativity towards the substrate N-carbamoyl-beta-alanine. Such allosteric regulation of this enzyme is consistent with the recently recognized pleiotropic physiological roles of beta-alanine: it functions in the brain as a neurotransmitter, in the activation of ion channels, and in the formation of the neural dipeptides carnosine (beta-alanyl-histidine), anserine (beta-alanyl-methylhistidine), and beta-alanyl-hypusine. For humans, controlled beta-alanine production is very important, since abnormal beta-alanine metabolism in infants is associated with neural dysfunction, seizures, or death.



The enzyme is allosterically regulated by the substrate N-carbamoyl-beta-alanine, which causes association of the native hexamer to the active dodecamer, or by the product beta-alanine which causes dissociation to the inactive trimer.


Sequence of beta-alanine synthase, from rat:





The protein was shown to contain two zinc atoms per subunit, and two putative zinc-binding sites, formed by three residues, are shown in green and in red.



Relevant papers:


1. Matthews, M.M., Liao, W., Kvalnes-Krick, K.L., and Traut, T.W.  (1992) Beta-alanine Synthase: Purification and allosteric properties. Arch. Biochem. Biophys. 293, 254-263.


2. Kvalnes-Krick, K.L., and Traut, T.W.  (1993) Cloning, sequencing, and expression of a cDNA encoding beta-alanine synthase from rat liver. J. Biol. Chem. 268, 5686-5693.