Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers
- Autores
- Cerf, Nicole Talia; Faraj, Santiago Enrique; Valsecchi, Wanda M.; Rossi, Rolando Carlos; Montes, Monica Raquel
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- The gastric H,K-ATPase is a membrane protein found in the parietal cells of the stomach, where it couples H+ extrusion to the uptake of K+ , leading to the acidification of gastric juice (1). Acid-related diseases are an important public health issue where the mainstay of treatment has been the suppression of H,K-ATPase activity. As K+ plays a vital role in this catalytic cycle, for the dephosphorylation of the H,K-ATPase and the subsequent conformational changes, acid secretion can be inhibited by agents that are competitive with respect to K+ binding. This argument led in the past decades to the development of a new class of acid suppressants, known as potassium competitive acid blockers (P-CABs). Since a systematic investigation of enzyme-inhibition mechanisms has become a fruitful way to design and test new drugs, the effects of P-CABs-type inhibitors have been extensively studied analyzing how the apparent Michaelis and Menten parameters are affected (2). Working with the non-compartmentalized enzyme preparation, we analyzed the interactions between K+ , the H,K-ATPase, and two different inhibitors under steady state conditions. Our results from ATPase activity as a function of K+ concentration was described by a rational function where the maximal exponent on [K+] is 2. Data show that K+ , as a product, can inhibit the reaction steps that involve its release, which implies that ATPase activity would not obey the Michaelis-Menten equation. This can lead to mistakes when analysing the results according to variations in Vmax and KM . Here we propose a minimal model to describe the binding of K+ to different enzyme conformations and the inhibition by P-CABs compounds allowing a more realistic evaluation of their effects.
Fil: Cerf, Nicole Talia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Faraj, Santiago Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Valsecchi, Wanda M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Rossi, Rolando Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Montes, Monica Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
XLIX Reunión Anual de la Sociedad Argentina de Biofísica
Argentina
Sociedad Argentina de Biofísica - Materia
-
H,K-ATPasa
Inhibidores competitivos del potasio - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/197096
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Inhibition of the gastric H,K-ATPase by potassium competitive acid blockersCerf, Nicole TaliaFaraj, Santiago EnriqueValsecchi, Wanda M.Rossi, Rolando CarlosMontes, Monica RaquelH,K-ATPasaInhibidores competitivos del potasiohttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The gastric H,K-ATPase is a membrane protein found in the parietal cells of the stomach, where it couples H+ extrusion to the uptake of K+ , leading to the acidification of gastric juice (1). Acid-related diseases are an important public health issue where the mainstay of treatment has been the suppression of H,K-ATPase activity. As K+ plays a vital role in this catalytic cycle, for the dephosphorylation of the H,K-ATPase and the subsequent conformational changes, acid secretion can be inhibited by agents that are competitive with respect to K+ binding. This argument led in the past decades to the development of a new class of acid suppressants, known as potassium competitive acid blockers (P-CABs). Since a systematic investigation of enzyme-inhibition mechanisms has become a fruitful way to design and test new drugs, the effects of P-CABs-type inhibitors have been extensively studied analyzing how the apparent Michaelis and Menten parameters are affected (2). Working with the non-compartmentalized enzyme preparation, we analyzed the interactions between K+ , the H,K-ATPase, and two different inhibitors under steady state conditions. Our results from ATPase activity as a function of K+ concentration was described by a rational function where the maximal exponent on [K+] is 2. Data show that K+ , as a product, can inhibit the reaction steps that involve its release, which implies that ATPase activity would not obey the Michaelis-Menten equation. This can lead to mistakes when analysing the results according to variations in Vmax and KM . Here we propose a minimal model to describe the binding of K+ to different enzyme conformations and the inhibition by P-CABs compounds allowing a more realistic evaluation of their effects.Fil: Cerf, Nicole Talia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Faraj, Santiago Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Valsecchi, Wanda M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Rossi, Rolando Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Montes, Monica Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaXLIX Reunión Anual de la Sociedad Argentina de BiofísicaArgentinaSociedad Argentina de BiofísicaSociedad Argentina de Biofísica2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/197096Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers; XLIX Reunión Anual de la Sociedad Argentina de Biofísica; Argentina; 2021; 1-1978-987-27591-9-3CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/congreso-2021/#talksinfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:03:13Zoai:ri.conicet.gov.ar:11336/197096instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:03:13.865CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers |
title |
Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers |
spellingShingle |
Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers Cerf, Nicole Talia H,K-ATPasa Inhibidores competitivos del potasio |
title_short |
Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers |
title_full |
Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers |
title_fullStr |
Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers |
title_full_unstemmed |
Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers |
title_sort |
Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers |
dc.creator.none.fl_str_mv |
Cerf, Nicole Talia Faraj, Santiago Enrique Valsecchi, Wanda M. Rossi, Rolando Carlos Montes, Monica Raquel |
author |
Cerf, Nicole Talia |
author_facet |
Cerf, Nicole Talia Faraj, Santiago Enrique Valsecchi, Wanda M. Rossi, Rolando Carlos Montes, Monica Raquel |
author_role |
author |
author2 |
Faraj, Santiago Enrique Valsecchi, Wanda M. Rossi, Rolando Carlos Montes, Monica Raquel |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
H,K-ATPasa Inhibidores competitivos del potasio |
topic |
H,K-ATPasa Inhibidores competitivos del potasio |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
The gastric H,K-ATPase is a membrane protein found in the parietal cells of the stomach, where it couples H+ extrusion to the uptake of K+ , leading to the acidification of gastric juice (1). Acid-related diseases are an important public health issue where the mainstay of treatment has been the suppression of H,K-ATPase activity. As K+ plays a vital role in this catalytic cycle, for the dephosphorylation of the H,K-ATPase and the subsequent conformational changes, acid secretion can be inhibited by agents that are competitive with respect to K+ binding. This argument led in the past decades to the development of a new class of acid suppressants, known as potassium competitive acid blockers (P-CABs). Since a systematic investigation of enzyme-inhibition mechanisms has become a fruitful way to design and test new drugs, the effects of P-CABs-type inhibitors have been extensively studied analyzing how the apparent Michaelis and Menten parameters are affected (2). Working with the non-compartmentalized enzyme preparation, we analyzed the interactions between K+ , the H,K-ATPase, and two different inhibitors under steady state conditions. Our results from ATPase activity as a function of K+ concentration was described by a rational function where the maximal exponent on [K+] is 2. Data show that K+ , as a product, can inhibit the reaction steps that involve its release, which implies that ATPase activity would not obey the Michaelis-Menten equation. This can lead to mistakes when analysing the results according to variations in Vmax and KM . Here we propose a minimal model to describe the binding of K+ to different enzyme conformations and the inhibition by P-CABs compounds allowing a more realistic evaluation of their effects. Fil: Cerf, Nicole Talia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Faraj, Santiago Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Valsecchi, Wanda M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Rossi, Rolando Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Montes, Monica Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina XLIX Reunión Anual de la Sociedad Argentina de Biofísica Argentina Sociedad Argentina de Biofísica |
description |
The gastric H,K-ATPase is a membrane protein found in the parietal cells of the stomach, where it couples H+ extrusion to the uptake of K+ , leading to the acidification of gastric juice (1). Acid-related diseases are an important public health issue where the mainstay of treatment has been the suppression of H,K-ATPase activity. As K+ plays a vital role in this catalytic cycle, for the dephosphorylation of the H,K-ATPase and the subsequent conformational changes, acid secretion can be inhibited by agents that are competitive with respect to K+ binding. This argument led in the past decades to the development of a new class of acid suppressants, known as potassium competitive acid blockers (P-CABs). Since a systematic investigation of enzyme-inhibition mechanisms has become a fruitful way to design and test new drugs, the effects of P-CABs-type inhibitors have been extensively studied analyzing how the apparent Michaelis and Menten parameters are affected (2). Working with the non-compartmentalized enzyme preparation, we analyzed the interactions between K+ , the H,K-ATPase, and two different inhibitors under steady state conditions. Our results from ATPase activity as a function of K+ concentration was described by a rational function where the maximal exponent on [K+] is 2. Data show that K+ , as a product, can inhibit the reaction steps that involve its release, which implies that ATPase activity would not obey the Michaelis-Menten equation. This can lead to mistakes when analysing the results according to variations in Vmax and KM . Here we propose a minimal model to describe the binding of K+ to different enzyme conformations and the inhibition by P-CABs compounds allowing a more realistic evaluation of their effects. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 |
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info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/conferenceObject Reunión Book http://purl.org/coar/resource_type/c_5794 info:ar-repo/semantics/documentoDeConferencia |
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publishedVersion |
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conferenceObject |
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http://hdl.handle.net/11336/197096 Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers; XLIX Reunión Anual de la Sociedad Argentina de Biofísica; Argentina; 2021; 1-1 978-987-27591-9-3 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/197096 |
identifier_str_mv |
Inhibition of the gastric H,K-ATPase by potassium competitive acid blockers; XLIX Reunión Anual de la Sociedad Argentina de Biofísica; Argentina; 2021; 1-1 978-987-27591-9-3 CONICET Digital CONICET |
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eng |
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eng |
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Sociedad Argentina de Biofísica |
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Sociedad Argentina de Biofísica |
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