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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Detalles Bibliográficos
Autor principal: Kotler, M.L
Otros Autores: Juknat, A.A, Correa Garcia, S.R, Princ, F., Del Batlle, C.A.M
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 1988
Acceso en línea:Registro en Scopus
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Registro en la Biblioteca Digital
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024 7 |2 cas  |a folic acid, 59-30-3, 6484-89-5; porphobilinogen deaminase, 9036-47-9, 9074-91-3; sulfamerazine, 127-58-2, 127-79-7 
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100 1 |a Kotler, M.L. 
245 1 3 |a In vitro sulphamerazine inhibition of rat blood uroporhyrinogen I synthetase and its reversal by folic acid 
260 |c 1988 
506 |2 openaire  |e Política editorial 
520 3 |a 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.  |l eng 
593 |a Centro de Investigaciones sobre Porfirinas y Porfirias, CIPYP, Ciudad Universitaria, 1428 Buenos Aires, Argentina 
690 1 0 |a FOLIC ACID 
690 1 0 |a PORPHOBILINOGEN DEAMINASE 
690 1 0 |a SULFAMERAZINE 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a HEME SYNTHESIS 
690 1 0 |a MALE 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a RAT 
690 1 0 |a ANIMALIA 
700 1 |a Juknat, A.A. 
700 1 |a Correa Garcia, S.R. 
700 1 |a Princ, F. 
700 1 |a Del Batlle, C.A.M. 
773 0 |d 1988  |g v. 16  |h pp. 983-984  |k n. 18  |p MED. SCI. RES.  |x 02698951  |t Medical Science Research 
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