Alkaline phosphatases [ALPases; orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] from dog and human placenta, liver, bone, kidney, and intestine were investigated by inhibition studies with Lhomoarginine, L-phenylalanine, and L-phenylalanylglycylglycine; by thermostability studies; and by electrophoresis, both before and after treatment with neuraminidase. The inhibitions obtained for each inhibitor with dog placental ALPase closely match those obtained with dog and human liver, bone, and kidney ALPases, but are quite different from those obtained with human placental ALPase. Dog placental ALPase is thermolabile, as are dog and human liver, bone, and kidney ALPases, in marked contrast to human placental ALPase, which is very thermostable. Dog placental ALPase has the same electrophoretic mobility as dog liver, bone, and kidney ALPases after removal of sialic acid residues with neuraminidase. Desialated human placental ALPase differs electrophoretically from desialated human liver, bone, and kidney ALPases, which show the same mobilities. Dog and human intestinal ALPases are distinguished by these various criteria from the liver, bone, kidney, and placental ALPases of both species, but are similar to each other. These results suggest that the ALPase gene locus expressed in dog placenta is not homologous to that expressed in human placenta. Rather, it appears to be homologous to the ALPase locus expressed in dog and human liver and possibly also bone and kidney. Other incomplete data suggest that this may also be true for placental ALPase in other mammalian species. One possible explanation is that human placental ALPase, a relatively recent newcomer on the evolutionary scene, arose from a gene duplication that occurred subsequent to the evolutionary divergence of many other mammalian species.The alkaline phosphatases [ALPases; orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] are a group of similar enzymes that hydrolyze various monophosphate esters. They are glycoproteins (1-4) named for the different tissues in which they predominate, the best characterized forms being those from liver, bone, kidney, intestine, and placenta (5). Several lines of evidence (summarized in refs. 6 and 7) suggest that in man the various ALPases are determined by at least three gene loci: one coding for the placental enzyme, at least one coding for the intestinal enzyme, and at least one coding for the liver, bone, and kidney forms of the enzyme. In the case of intestinal ALPase, electrophoretic differences between adult and fetal forms occur (7), and, in the case of liver and bone ALPases, thermostability (8, 9) and immunologic differences (10, 11) have been reported. It is not yet clear in either of these cases whether posttranslational changes or separate loci account for these differences.Various techniques have been used to distinguish between the three main types of human ALPase. They can, for example, be differentiated by inhibition studies with certain amino acids an...
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.
Thi inhibits Phe tubular resorption and also causes tion of Phe in animals. Structural similarities between Phe and Thi suggested Thi may be a good inhibitor of PheH and hence reproduce the biochemical lesion in PKU. The effects of Thi on rat liver (Lv) and kidney (Kd) PheH were assessed !2
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.