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Bongkrekic Acid—a Review of a Lesser-Known Mitochondrial Toxin

Introduction Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans ( B. cocovenenans )...

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Published in:Journal of medical toxicology 2017-06, Vol.13 (2), p.173-179
Main Authors: Anwar, Mehruba, Kasper, Amelia, Steck, Alaina R., Schier, Joshua G.
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description Introduction Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans ( B. cocovenenans ) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning. Methods We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index ( http://id.portalgaruda.org/ ), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive. Conclusions Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.
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Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans ( B. cocovenenans ) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning. Methods We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index ( http://id.portalgaruda.org/ ), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive. Conclusions Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.</description><identifier>ISSN: 1556-9039</identifier><identifier>EISSN: 1937-6995</identifier><identifier>DOI: 10.1007/s13181-016-0577-1</identifier><identifier>PMID: 28105575</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adenine ; Animals ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Bongkrekic Acid - pharmacokinetics ; Bongkrekic Acid - poisoning ; Burkholderia gladioli - metabolism ; Burkholderia gladioli - pathogenicity ; Burkholderia Infections - enzymology ; Burkholderia Infections - epidemiology ; Burkholderia Infections - microbiology ; Burkholderia Infections - therapy ; Cadmium selenide ; Cocos - microbiology ; Corn ; Electron transport ; Electron transport chain ; Epidemiology ; Fatty acids ; Food ; Food Microbiology ; Food poisoning ; Foodborne diseases ; Foodborne Diseases - enzymology ; Foodborne Diseases - epidemiology ; Foodborne Diseases - microbiology ; Foodborne Diseases - therapy ; Illnesses ; Mitochondria ; Mitochondria - enzymology ; Mitochondria - pathology ; Mitochondrial ADP, ATP Translocases - antagonists &amp; inhibitors ; Mitochondrial ADP, ATP Translocases - metabolism ; Molecular weight ; Nucleotides ; Outbreaks ; Pharmacology/Toxicology ; Poisoning ; Poisons ; Review ; Search engines ; Signs and symptoms ; Thermal stability ; Toxicity ; Toxins ; Translocase ; Treatment Outcome ; Zea mays - microbiology</subject><ispartof>Journal of medical toxicology, 2017-06, Vol.13 (2), p.173-179</ispartof><rights>American College of Medical Toxicology 2017</rights><rights>Journal of Medical Toxicology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-9838ae466663b48e4fd6c85d03ec0b2201861403dc31120a99ba4cfc566a3ff53</citedby><cites>FETCH-LOGICAL-c470t-9838ae466663b48e4fd6c85d03ec0b2201861403dc31120a99ba4cfc566a3ff53</cites><orcidid>0000-0002-3551-2749</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440313/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440313/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28105575$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anwar, Mehruba</creatorcontrib><creatorcontrib>Kasper, Amelia</creatorcontrib><creatorcontrib>Steck, Alaina R.</creatorcontrib><creatorcontrib>Schier, Joshua G.</creatorcontrib><title>Bongkrekic Acid—a Review of a Lesser-Known Mitochondrial Toxin</title><title>Journal of medical toxicology</title><addtitle>J. Med. Toxicol</addtitle><addtitle>J Med Toxicol</addtitle><description>Introduction Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans ( B. cocovenenans ) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning. Methods We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index ( http://id.portalgaruda.org/ ), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive. Conclusions Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.</description><subject>Adenine</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bongkrekic Acid - pharmacokinetics</subject><subject>Bongkrekic Acid - poisoning</subject><subject>Burkholderia gladioli - metabolism</subject><subject>Burkholderia gladioli - pathogenicity</subject><subject>Burkholderia Infections - enzymology</subject><subject>Burkholderia Infections - epidemiology</subject><subject>Burkholderia Infections - microbiology</subject><subject>Burkholderia Infections - therapy</subject><subject>Cadmium selenide</subject><subject>Cocos - microbiology</subject><subject>Corn</subject><subject>Electron transport</subject><subject>Electron transport chain</subject><subject>Epidemiology</subject><subject>Fatty acids</subject><subject>Food</subject><subject>Food Microbiology</subject><subject>Food poisoning</subject><subject>Foodborne diseases</subject><subject>Foodborne Diseases - enzymology</subject><subject>Foodborne Diseases - epidemiology</subject><subject>Foodborne Diseases - microbiology</subject><subject>Foodborne Diseases - therapy</subject><subject>Illnesses</subject><subject>Mitochondria</subject><subject>Mitochondria - enzymology</subject><subject>Mitochondria - pathology</subject><subject>Mitochondrial ADP, ATP Translocases - antagonists &amp; inhibitors</subject><subject>Mitochondrial ADP, ATP Translocases - metabolism</subject><subject>Molecular weight</subject><subject>Nucleotides</subject><subject>Outbreaks</subject><subject>Pharmacology/Toxicology</subject><subject>Poisoning</subject><subject>Poisons</subject><subject>Review</subject><subject>Search engines</subject><subject>Signs and symptoms</subject><subject>Thermal stability</subject><subject>Toxicity</subject><subject>Toxins</subject><subject>Translocase</subject><subject>Treatment Outcome</subject><subject>Zea mays - microbiology</subject><issn>1556-9039</issn><issn>1937-6995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp1kM1OAyEUhYnRaP15ADdmEtcodxhmYGOsjX-xxsTomlCGqWgLFdqqOx_CJ_RJpJlqdCEb7s0999yTD6FdIAdASHUYgQIHTKDEhFUVhhXUAUErXArBVlPNWIkFoWIDbcb4SEjq82IdbeQcUl2xDjo-8W74FMyT1VlX2_rz_UNlt2ZuzUvmm0xlfROjCfjK-ReXXdup1w_e1cGqUXbnX63bRmuNGkWzs_y30P3Z6V3vAvdvzi973T7WRUWmWHDKlSnK9Oig4KZo6lJzVhNqNBnkOQFeQkForSlATpQQA1XoRrOyVLRpGN1CR63vZDYYm1obNw1qJCfBjlV4k15Z-Xfi7IMc-rlkRbIFmgz2lwbBP89MnMpHPwsuZZYgCABPOXlSQavSwccYTPNzAYhcQJctdJmgywV0CWln73e0n41vykmQt4KYRm5owq_T_7p-AYlEjQ0</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Anwar, Mehruba</creator><creator>Kasper, Amelia</creator><creator>Steck, Alaina R.</creator><creator>Schier, Joshua G.</creator><general>Springer US</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3551-2749</orcidid></search><sort><creationdate>20170601</creationdate><title>Bongkrekic Acid—a Review of a Lesser-Known Mitochondrial Toxin</title><author>Anwar, Mehruba ; Kasper, Amelia ; Steck, Alaina R. ; Schier, Joshua G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-9838ae466663b48e4fd6c85d03ec0b2201861403dc31120a99ba4cfc566a3ff53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adenine</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bongkrekic Acid - pharmacokinetics</topic><topic>Bongkrekic Acid - poisoning</topic><topic>Burkholderia gladioli - metabolism</topic><topic>Burkholderia gladioli - pathogenicity</topic><topic>Burkholderia Infections - enzymology</topic><topic>Burkholderia Infections - epidemiology</topic><topic>Burkholderia Infections - microbiology</topic><topic>Burkholderia Infections - therapy</topic><topic>Cadmium selenide</topic><topic>Cocos - microbiology</topic><topic>Corn</topic><topic>Electron transport</topic><topic>Electron transport chain</topic><topic>Epidemiology</topic><topic>Fatty acids</topic><topic>Food</topic><topic>Food Microbiology</topic><topic>Food poisoning</topic><topic>Foodborne diseases</topic><topic>Foodborne Diseases - enzymology</topic><topic>Foodborne Diseases - epidemiology</topic><topic>Foodborne Diseases - microbiology</topic><topic>Foodborne Diseases - therapy</topic><topic>Illnesses</topic><topic>Mitochondria</topic><topic>Mitochondria - enzymology</topic><topic>Mitochondria - pathology</topic><topic>Mitochondrial ADP, ATP Translocases - antagonists &amp; inhibitors</topic><topic>Mitochondrial ADP, ATP Translocases - metabolism</topic><topic>Molecular weight</topic><topic>Nucleotides</topic><topic>Outbreaks</topic><topic>Pharmacology/Toxicology</topic><topic>Poisoning</topic><topic>Poisons</topic><topic>Review</topic><topic>Search engines</topic><topic>Signs and symptoms</topic><topic>Thermal stability</topic><topic>Toxicity</topic><topic>Toxins</topic><topic>Translocase</topic><topic>Treatment Outcome</topic><topic>Zea mays - microbiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anwar, Mehruba</creatorcontrib><creatorcontrib>Kasper, Amelia</creatorcontrib><creatorcontrib>Steck, Alaina R.</creatorcontrib><creatorcontrib>Schier, Joshua G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Toxicology Abstracts</collection><collection>ProQuest Health &amp; 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Med. Toxicol</stitle><addtitle>J Med Toxicol</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>13</volume><issue>2</issue><spage>173</spage><epage>179</epage><pages>173-179</pages><issn>1556-9039</issn><eissn>1937-6995</eissn><abstract>Introduction Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans ( B. cocovenenans ) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning. Methods We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index ( http://id.portalgaruda.org/ ), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive. Conclusions Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28105575</pmid><doi>10.1007/s13181-016-0577-1</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3551-2749</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adenine
Animals
Apoptosis
Biomedical and Life Sciences
Biomedicine
Bongkrekic Acid - pharmacokinetics
Bongkrekic Acid - poisoning
Burkholderia gladioli - metabolism
Burkholderia gladioli - pathogenicity
Burkholderia Infections - enzymology
Burkholderia Infections - epidemiology
Burkholderia Infections - microbiology
Burkholderia Infections - therapy
Cadmium selenide
Cocos - microbiology
Corn
Electron transport
Electron transport chain
Epidemiology
Fatty acids
Food
Food Microbiology
Food poisoning
Foodborne diseases
Foodborne Diseases - enzymology
Foodborne Diseases - epidemiology
Foodborne Diseases - microbiology
Foodborne Diseases - therapy
Illnesses
Mitochondria
Mitochondria - enzymology
Mitochondria - pathology
Mitochondrial ADP, ATP Translocases - antagonists & inhibitors
Mitochondrial ADP, ATP Translocases - metabolism
Molecular weight
Nucleotides
Outbreaks
Pharmacology/Toxicology
Poisoning
Poisons
Review
Search engines
Signs and symptoms
Thermal stability
Toxicity
Toxins
Translocase
Treatment Outcome
Zea mays - microbiology
title Bongkrekic Acid—a Review of a Lesser-Known Mitochondrial Toxin
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