1. Transamination in the metabolism of beta-2-thienyl-DL-alanine in normal and neoplastic cells in vitro
J A JACQUEZ, R K BARCLAY, C C STOCK J Exp Med. 1952 Nov;96(5):499-512. doi: 10.1084/jem.96.5.499.
In tissue cultures of C-57 black mouse heart and sarcoma T-241, beta-2-thienyl-DL-alanine acts specifically as a phenylalanine antagonist. Heart cultures can transaminate between beta-2-thienyl-DL-alanine and phenylpyruvate to form L-phenylalanine and thus block the toxic action of the remaining beta-2-thienyl-DL-alanine, whereas sarcoma T-241 cultures cannot. Of eleven mouse tumors and four rat tumors tested for their ability to perform this reaction, nine tumors had little or no activity. The beta-2-thienylpyruvic acid resulting from transamination further reacts to form a red compound the exact structure of which is not yet known.
3. beta-2-Thienyl-DL-alanine as an inhibitor of phenylalanine hydroxylase and phenylalanine intestinal transport
R A Wapnir, G S Moak Biochem J. 1979 Jan 1;177(1):347-52. doi: 10.1042/bj1770347.
The inhibitory properties of beta-2-thienyl-dl-alanine on rat phenylalanine hydroxylase from crude liver and kidney homogenates were assessed in vitro and in vivo, as well as its effects on the intestinal transport of phenylalanine, by using a perfusion procedure in vivo. The apparent K(m) for liver phenylalanine hydroxylase changed from 0.61mm in the absence of the inhibitor to 2.70mm in the presence of 24mm-beta-2-thienyl-dl-alanine, with no significant change in the V(max.). For kidney the corresponding values were 0.50 and 1.60mm respectively. A single dose of beta-2-thienyl-dl-alanine (2mmol/kg) failed to inhibit phenylalanine hydroxylase in either organ. Repeated injections during a 4-day period caused a decline of the enzymic activity to about 40% of controls. Intestinal absorption of phenylalanine when perfused at 0.2-2.0mm concentration was also competitively inhibited by beta-2-thienyl-dl-alanine. Its K(i) value was estimated at 81mm. The limited inhibitory effects of beta-2-thienyl-dl-alanine towards hepatic phenylalanine hydroxylase and phenylalanine intestinal transport, and its rapid metabolism, as suggested by the small elimination of this compound in the urine and its virtual absence from animal tissues, are factors that restrict its potential usefulness as an inducer of phenylketonuria in rats or as an effective blocker of phenylalanine absorption by the gut.
