In vitro sulphamerazine inhibition of rat blood uroporhyrinogen I synthetase and its reversal by folic acid
It has been reported that sulphamerazine (SMZ) produced a 30% inhibition of blood URO-S, 8 h after i.p. injection in rats. These results prompted us to investigate if SMZ exerted the same effect in vitro, and if this was so, to establish if folic acid could revert such effect, with the final purpose...
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1988
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02698951_v16_n18_p983_Kotler http://hdl.handle.net/20.500.12110/paper_02698951_v16_n18_p983_Kotler |
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paper:paper_02698951_v16_n18_p983_Kotler2023-06-08T15:24:33Z In vitro sulphamerazine inhibition of rat blood uroporhyrinogen I synthetase and its reversal by folic acid folic acid porphobilinogen deaminase sulfamerazine animal experiment animal model heme synthesis male nonhuman priority journal rat Animalia It has been reported that sulphamerazine (SMZ) produced a 30% inhibition of blood URO-S, 8 h after i.p. injection in rats. These results prompted us to investigate if SMZ exerted the same effect in vitro, and if this was so, to establish if folic acid could revert such effect, with the final purpose of carrying out in vivo studies. An incubation temperature of 60°C for blood URO-S was determined as optimal for 100% uroporphyrinogen I formation. Maximal in vitro inhibition of URO-S activity (55%) measured at 60°C was observed at 3 mM SMZ. Increasing concentrations of the drug did not enhance this inhibition. 1 mM folic acid can revert SMZ inhibition, between 80 and 100%, depending on the concentration of inhibitor tested (0.01-5 mM). However, folic acid reversion of SMZ inhibition was also dependent on the relative concentration of the former drug. So 4 mM folic acid completely abolished the maximal inhibition observed at 3 mM. The present results suggest that during incubations at 60°C, SMZ would bind URO-S. By adding exogenous folate a reversal of the SMZ effect was found, very likely by displacement on the same regulatory site on the enzyme. In contrast, SMZ (0-5 mM) did not alter blood uroporphyrinogen III biosynthesis suggesting that cosynthetase could play a protective role on URO-S, mediated by the binding of folic acid on the latter enzyme. 1988 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02698951_v16_n18_p983_Kotler http://hdl.handle.net/20.500.12110/paper_02698951_v16_n18_p983_Kotler |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
folic acid porphobilinogen deaminase sulfamerazine animal experiment animal model heme synthesis male nonhuman priority journal rat Animalia |
| spellingShingle |
folic acid porphobilinogen deaminase sulfamerazine animal experiment animal model heme synthesis male nonhuman priority journal rat Animalia In vitro sulphamerazine inhibition of rat blood uroporhyrinogen I synthetase and its reversal by folic acid |
| topic_facet |
folic acid porphobilinogen deaminase sulfamerazine animal experiment animal model heme synthesis male nonhuman priority journal rat Animalia |
| description |
It has been reported that sulphamerazine (SMZ) produced a 30% inhibition of blood URO-S, 8 h after i.p. injection in rats. These results prompted us to investigate if SMZ exerted the same effect in vitro, and if this was so, to establish if folic acid could revert such effect, with the final purpose of carrying out in vivo studies. An incubation temperature of 60°C for blood URO-S was determined as optimal for 100% uroporphyrinogen I formation. Maximal in vitro inhibition of URO-S activity (55%) measured at 60°C was observed at 3 mM SMZ. Increasing concentrations of the drug did not enhance this inhibition. 1 mM folic acid can revert SMZ inhibition, between 80 and 100%, depending on the concentration of inhibitor tested (0.01-5 mM). However, folic acid reversion of SMZ inhibition was also dependent on the relative concentration of the former drug. So 4 mM folic acid completely abolished the maximal inhibition observed at 3 mM. The present results suggest that during incubations at 60°C, SMZ would bind URO-S. By adding exogenous folate a reversal of the SMZ effect was found, very likely by displacement on the same regulatory site on the enzyme. In contrast, SMZ (0-5 mM) did not alter blood uroporphyrinogen III biosynthesis suggesting that cosynthetase could play a protective role on URO-S, mediated by the binding of folic acid on the latter enzyme. |
| title |
In vitro sulphamerazine inhibition of rat blood uroporhyrinogen I synthetase and its reversal by folic acid |
| title_short |
In vitro sulphamerazine inhibition of rat blood uroporhyrinogen I synthetase and its reversal by folic acid |
| title_full |
In vitro sulphamerazine inhibition of rat blood uroporhyrinogen I synthetase and its reversal by folic acid |
| title_fullStr |
In vitro sulphamerazine inhibition of rat blood uroporhyrinogen I synthetase and its reversal by folic acid |
| title_full_unstemmed |
In vitro sulphamerazine inhibition of rat blood uroporhyrinogen I synthetase and its reversal by folic acid |
| title_sort |
in vitro sulphamerazine inhibition of rat blood uroporhyrinogen i synthetase and its reversal by folic acid |
| publishDate |
1988 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02698951_v16_n18_p983_Kotler http://hdl.handle.net/20.500.12110/paper_02698951_v16_n18_p983_Kotler |
| _version_ |
1768544909713735680 |