Metabolism of Beta-Alanine in Rat Liver: Degradation to Acetyl-CoA and Carboxylation to 2-(aminomethyl)-malonate

Beta-alanine (BA) is a product of uracil and 3-hydroxypropionate catabolism. BA is a precursor of the dipeptides carnosine and anserine, which play an important role in the pH homeostasis of muscle during exercise. BA is used by athletes as a nutritional supplement to increase performance during strenuous exercise. However, an unwanted side-effect of the ingestion of BA is unpleasant paresthesia, the mechanism of which is unknown. As part of a study of 3-hydroxypropionate metabolism, we perfused rat livers with 2 mM [15N, 13C3]BA (M4 BA). A metabolomic study of the liver showed that acetyl-CoA was 12% M2 labeled, reflecting oxidation of BA in the citric acid cycle. Urea was 15N-labeled further confirming the catabolism of BA. We also identified a new compound with a molecular weight equal to BA + 4 + 44. This suggested that BA was carboxylated (MW of CO2 = 44). This was confirmed by perfusing livers with unlabeled BA + either unlabeled NaHCO3 or NaH13CO3; the MW of the new compound was BA + 44 or BA + 45....