Studies on the mechanism of the antifungal action of benzoate
A method is described for the determination of the pH of intracellular water based on the distribution of [14C]benzoate (0.01 mM) between intra- and extra-cellular water. Benzoate at higher concentrations (2-10mM) enters the yeast cell in the undissociated form, and its neutralization within the cel...
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| Veröffentlicht in: | Biochemical journal 1983-09, Vol.214 (3), p.657-663 |
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| container_end_page | 663 |
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| container_issue | 3 |
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| container_title | Biochemical journal |
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| creator | Krebs, H.A Wiggins, D Stubbs, M Sols, A Bedoya, F |
| description | A method is described for the determination of the pH of intracellular water based on the distribution of [14C]benzoate (0.01 mM) between intra- and extra-cellular water. Benzoate at higher concentrations (2-10mM) enters the yeast cell in the undissociated form, and its neutralization within the cell can cause a shift of the pH of the intracellular water by more than 1 pH unit. Benzoate causes an accumulation of the two hexose monophosphates of yeast glucose fermentation and a decrease in intermediates beyond phosphofructokinase, suggesting inhibition at this stage. Benzoate also causes a concomitant fall in [ATP]. Phosphofructokinase is inhibited to a greater extent than hexokinase at acid pH. There is a relationship between intracellular pH, phosphofructokinase inhibition and CO2 production, suggesting that the antifungal action of benzoate is caused by an accumulation of benzoate at low external pH, which lowers the intracellular pH into the range where phosphofructokinase is sensitive. The subsequent inhibition of glycolysis causes a fall in [ATP] and thus restricts growth. |
| doi_str_mv | 10.1042/bj2140657 |
| format | Article |
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Benzoate at higher concentrations (2-10mM) enters the yeast cell in the undissociated form, and its neutralization within the cell can cause a shift of the pH of the intracellular water by more than 1 pH unit. Benzoate causes an accumulation of the two hexose monophosphates of yeast glucose fermentation and a decrease in intermediates beyond phosphofructokinase, suggesting inhibition at this stage. Benzoate also causes a concomitant fall in [ATP]. Phosphofructokinase is inhibited to a greater extent than hexokinase at acid pH. There is a relationship between intracellular pH, phosphofructokinase inhibition and CO2 production, suggesting that the antifungal action of benzoate is caused by an accumulation of benzoate at low external pH, which lowers the intracellular pH into the range where phosphofructokinase is sensitive. 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Benzoate at higher concentrations (2-10mM) enters the yeast cell in the undissociated form, and its neutralization within the cell can cause a shift of the pH of the intracellular water by more than 1 pH unit. Benzoate causes an accumulation of the two hexose monophosphates of yeast glucose fermentation and a decrease in intermediates beyond phosphofructokinase, suggesting inhibition at this stage. Benzoate also causes a concomitant fall in [ATP]. Phosphofructokinase is inhibited to a greater extent than hexokinase at acid pH. There is a relationship between intracellular pH, phosphofructokinase inhibition and CO2 production, suggesting that the antifungal action of benzoate is caused by an accumulation of benzoate at low external pH, which lowers the intracellular pH into the range where phosphofructokinase is sensitive. The subsequent inhibition of glycolysis causes a fall in [ATP] and thus restricts growth.</description><subject>Adenine Nucleotides - metabolism</subject><subject>Anaerobiosis</subject><subject>Antifungal Agents - pharmacology</subject><subject>bakers yeast</subject><subject>Benzoates - pharmacology</subject><subject>Benzoic Acid</subject><subject>Carbon Dioxide - metabolism</subject><subject>Fermentation - drug effects</subject><subject>Hexokinase - metabolism</subject><subject>Hydrogen-Ion Concentration</subject><subject>Phosphofructokinase-1 - metabolism</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae - drug effects</subject><subject>Saccharomyces cerevisiae - metabolism</subject><issn>0306-3283</issn><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1983</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkF9LwzAUxYMoc04f_ABinwQfqjdJ0yYPCjL8BwMf5p5DmqRbRtto0wr66Y1uDH26cM6Pcw8HoVMMVxgycl2uCc4gZ8UeGuOsgJQXhO-jMVDIU0o4PURHIawBIpXBCI1yQvIoj9HNvB-MsyHxbdKvbNJYvVKtC03iq19Btb2rhnap6kTp3kUsGqVtv7zq7TE6qFQd7Mn2TtDi4f51-pTOXh6fp3ezVFMQRSpwYStGOKhSGG5KoUBjynMWu1JTguKcFZZqI3SuhC4gM5STLOcWGBXY0Am63eS-DWVjjbZt36lavnWuUd2n9MrJ_07rVnLpPyTGjFCAGHCxDej8-2BDLxsXtK1r1Vo_BMkhF5QJGsHLDag7H0Jnq90TDPJna7nbOrJnf1vtyO240T_f-JXyUi07F-RiTgBTIAQ4YZR-A4eCgiQ</recordid><startdate>19830915</startdate><enddate>19830915</enddate><creator>Krebs, H.A</creator><creator>Wiggins, D</creator><creator>Stubbs, M</creator><creator>Sols, A</creator><creator>Bedoya, F</creator><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19830915</creationdate><title>Studies on the mechanism of the antifungal action of benzoate</title><author>Krebs, H.A ; Wiggins, D ; Stubbs, M ; Sols, A ; Bedoya, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3097-917ef5280ab9d8db9a0c138651473db0a8857e3cd9c6a9c704d382468e05391d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1983</creationdate><topic>Adenine Nucleotides - metabolism</topic><topic>Anaerobiosis</topic><topic>Antifungal Agents - pharmacology</topic><topic>bakers yeast</topic><topic>Benzoates - pharmacology</topic><topic>Benzoic Acid</topic><topic>Carbon Dioxide - metabolism</topic><topic>Fermentation - drug effects</topic><topic>Hexokinase - metabolism</topic><topic>Hydrogen-Ion Concentration</topic><topic>Phosphofructokinase-1 - metabolism</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae - drug effects</topic><topic>Saccharomyces cerevisiae - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krebs, H.A</creatorcontrib><creatorcontrib>Wiggins, D</creatorcontrib><creatorcontrib>Stubbs, M</creatorcontrib><creatorcontrib>Sols, A</creatorcontrib><creatorcontrib>Bedoya, F</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krebs, H.A</au><au>Wiggins, D</au><au>Stubbs, M</au><au>Sols, A</au><au>Bedoya, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Studies on the mechanism of the antifungal action of benzoate</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>1983-09-15</date><risdate>1983</risdate><volume>214</volume><issue>3</issue><spage>657</spage><epage>663</epage><pages>657-663</pages><issn>0306-3283</issn><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>A method is described for the determination of the pH of intracellular water based on the distribution of [14C]benzoate (0.01 mM) between intra- and extra-cellular water. Benzoate at higher concentrations (2-10mM) enters the yeast cell in the undissociated form, and its neutralization within the cell can cause a shift of the pH of the intracellular water by more than 1 pH unit. Benzoate causes an accumulation of the two hexose monophosphates of yeast glucose fermentation and a decrease in intermediates beyond phosphofructokinase, suggesting inhibition at this stage. Benzoate also causes a concomitant fall in [ATP]. Phosphofructokinase is inhibited to a greater extent than hexokinase at acid pH. There is a relationship between intracellular pH, phosphofructokinase inhibition and CO2 production, suggesting that the antifungal action of benzoate is caused by an accumulation of benzoate at low external pH, which lowers the intracellular pH into the range where phosphofructokinase is sensitive. The subsequent inhibition of glycolysis causes a fall in [ATP] and thus restricts growth.</abstract><cop>England</cop><pmid>6226283</pmid><doi>10.1042/bj2140657</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0306-3283 |
| ispartof | Biochemical journal, 1983-09, Vol.214 (3), p.657-663 |
| issn | 0306-3283 0264-6021 1470-8728 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Adenine Nucleotides - metabolism Anaerobiosis Antifungal Agents - pharmacology bakers yeast Benzoates - pharmacology Benzoic Acid Carbon Dioxide - metabolism Fermentation - drug effects Hexokinase - metabolism Hydrogen-Ion Concentration Phosphofructokinase-1 - metabolism Saccharomyces cerevisiae Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - metabolism |
| title | Studies on the mechanism of the antifungal action of benzoate |
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