beta-2-Thienyl-DL-alanine as an inhibitor of phenylalanine hydroxylase and phenylalanine intestinal transport

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...

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Bibliographic Details
Published in:Biochemical journal 1979-01, Vol.177 (1), p.347-352
Main Authors: Wapnir, R A, Moak, G S
Format: Article
Language:English
Subjects:
Alanine - analogs & derivatives
Alanine - pharmacology
Animals
Enzymology
In Vitro Techniques
Intestinal Absorption - drug effects
Jejunum - drug effects
Jejunum - metabolism
Kidney - enzymology
Kinetics
Liver - enzymology
Male
Phenylalanine - metabolism
Phenylalanine Hydroxylase - antagonists & inhibitors
Rats
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Summary: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.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj1770347