Glyoxylate reductase: Definitive identification in human liver mitochondria, its importance for the compartment‐specific detoxification of glyoxylate
Glyoxylate is a key metabolite generated from various precursor substrates in different subcellular compartments including mitochondria, peroxisomes, and the cytosol. The fact that glyoxylate is a good substrate for the ubiquitously expressed enzyme lactate dehydrogenase (LDH) requires the presence...
Gespeichert in:
| Veröffentlicht in: | Journal of inherited metabolic disease 2024-03, Vol.47 (2), p.280-288 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 288 |
|---|---|
| container_issue | 2 |
| container_start_page | 280 |
| container_title | Journal of inherited metabolic disease |
| container_volume | 47 |
| creator | Garrelfs, Sander F. Chornyi, Serhii Brinke, Heleen Ruiter, Jos Groothoff, Jaap Wanders, Ronald J. A. |
| description | Glyoxylate is a key metabolite generated from various precursor substrates in different subcellular compartments including mitochondria, peroxisomes, and the cytosol. The fact that glyoxylate is a good substrate for the ubiquitously expressed enzyme lactate dehydrogenase (LDH) requires the presence of efficient glyoxylate detoxification systems to avoid the formation of oxalate. Furthermore, this detoxification needs to be compartment‐specific since LDH is actively present in multiple subcellular compartments including peroxisomes, mitochondria, and the cytosol. Whereas the identity of these protection systems has been established for both peroxisomes and the cytosol as concluded from the deficiency of alanine glyoxylate aminotransferase (AGT) in primary hyperoxaluria type 1 (PH1) and glyoxylate reductase (GR) in PH2, the glyoxylate protection system in mitochondria has remained less well defined. In this manuscript, we show that the enzyme glyoxylate reductase has a bimodal distribution in human embryonic kidney (HEK293), hepatocellular carcinoma (HepG2), and cervical carcinoma (HeLa) cells and more importantly, in human liver, and is actively present in both the mitochondrial and cytosolic compartments. We conclude that the metabolism of glyoxylate in humans requires the complicated interaction between different subcellular compartments within the cell and discuss the implications for the different primary hyperoxalurias. |
| doi_str_mv | 10.1002/jimd.12711 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2913447710</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2913447710</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3931-63b26600b3a506ecb48ba0963a5331ab14e1ad6fb911e4928f5eede140b324ca3</originalsourceid><addsrcrecordid>eNp9kc9u1DAQhy1ERZfChQdAlrggRIon_pOEG2qhLSriAufIcSasV4kdbAe6Nx6BG-_Hk9TbLUXiwGk0mm8-zehHyBNgx8BY-Wpjp_4YygrgHlmBrHhRKiXvkxUDAUXdSHlIHsa4YYw1tZQPyCGvS8aUEivy62zc-qvtqBPSgP1iko74mp7iYJ1N9htS26NLdrBGJ-sdtY6ul0k7OuZhoJNN3qy964PVL6lNkdpp9iFpZ5AOPtC0Rmr8NOuQpiz6_eNnnNHsfLTH5K_-mv1Av9wd84gcDHqM-Pi2HpHP795-OjkvLj-eXZy8uSwMbzgUinf5V8Y6riVTaDpRd5o1Krecg-5AIOheDV0DgKIp60Ei9ggib5TCaH5Enu-9c_BfF4ypnWw0OI7aoV9iWzbAhagqYBl99g-68Utw-bpMyQqEkg3P1Is9ZYKPMeDQzsFOOmxbYO0urnYXV3sTV4af3iqXbsL-Dv2TTwZgD3y3I27_o2rfX3w43UuvATWipE0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2957146593</pqid></control><display><type>article</type><title>Glyoxylate reductase: Definitive identification in human liver mitochondria, its importance for the compartment‐specific detoxification of glyoxylate</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Garrelfs, Sander F. ; Chornyi, Serhii ; Brinke, Heleen ; Ruiter, Jos ; Groothoff, Jaap ; Wanders, Ronald J. A.</creator><creatorcontrib>Garrelfs, Sander F. ; Chornyi, Serhii ; Brinke, Heleen ; Ruiter, Jos ; Groothoff, Jaap ; Wanders, Ronald J. A.</creatorcontrib><description>Glyoxylate is a key metabolite generated from various precursor substrates in different subcellular compartments including mitochondria, peroxisomes, and the cytosol. The fact that glyoxylate is a good substrate for the ubiquitously expressed enzyme lactate dehydrogenase (LDH) requires the presence of efficient glyoxylate detoxification systems to avoid the formation of oxalate. Furthermore, this detoxification needs to be compartment‐specific since LDH is actively present in multiple subcellular compartments including peroxisomes, mitochondria, and the cytosol. Whereas the identity of these protection systems has been established for both peroxisomes and the cytosol as concluded from the deficiency of alanine glyoxylate aminotransferase (AGT) in primary hyperoxaluria type 1 (PH1) and glyoxylate reductase (GR) in PH2, the glyoxylate protection system in mitochondria has remained less well defined. In this manuscript, we show that the enzyme glyoxylate reductase has a bimodal distribution in human embryonic kidney (HEK293), hepatocellular carcinoma (HepG2), and cervical carcinoma (HeLa) cells and more importantly, in human liver, and is actively present in both the mitochondrial and cytosolic compartments. We conclude that the metabolism of glyoxylate in humans requires the complicated interaction between different subcellular compartments within the cell and discuss the implications for the different primary hyperoxalurias.</description><identifier>ISSN: 0141-8955</identifier><identifier>EISSN: 1573-2665</identifier><identifier>DOI: 10.1002/jimd.12711</identifier><identifier>PMID: 38200664</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Alcohol Oxidoreductases ; Cervical carcinoma ; Cytosol ; Detoxification ; Enzymes ; glyoxylate metabolism ; Glyoxylate reductase ; Glyoxylates - metabolism ; HEK293 Cells ; Hepatocellular carcinoma ; Humans ; hydroxyproline ; Hyperoxaluria ; L-Lactate dehydrogenase ; Liver ; Liver - metabolism ; Mitochondria ; Mitochondria, Liver - metabolism ; oxalate ; Oxalates - metabolism ; peroxisomal disorders ; Peroxisomes ; Primary hyperoxaluria ; Transaminases</subject><ispartof>Journal of inherited metabolic disease, 2024-03, Vol.47 (2), p.280-288</ispartof><rights>2024 The Authors. published by John Wiley & Sons Ltd on behalf of SSIEM.</rights><rights>2024 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3931-63b26600b3a506ecb48ba0963a5331ab14e1ad6fb911e4928f5eede140b324ca3</citedby><cites>FETCH-LOGICAL-c3931-63b26600b3a506ecb48ba0963a5331ab14e1ad6fb911e4928f5eede140b324ca3</cites><orcidid>0000-0002-6185-2616</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjimd.12711$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjimd.12711$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,1416,27915,27916,45565,45566</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38200664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Garrelfs, Sander F.</creatorcontrib><creatorcontrib>Chornyi, Serhii</creatorcontrib><creatorcontrib>Brinke, Heleen</creatorcontrib><creatorcontrib>Ruiter, Jos</creatorcontrib><creatorcontrib>Groothoff, Jaap</creatorcontrib><creatorcontrib>Wanders, Ronald J. A.</creatorcontrib><title>Glyoxylate reductase: Definitive identification in human liver mitochondria, its importance for the compartment‐specific detoxification of glyoxylate</title><title>Journal of inherited metabolic disease</title><addtitle>J Inherit Metab Dis</addtitle><description>Glyoxylate is a key metabolite generated from various precursor substrates in different subcellular compartments including mitochondria, peroxisomes, and the cytosol. The fact that glyoxylate is a good substrate for the ubiquitously expressed enzyme lactate dehydrogenase (LDH) requires the presence of efficient glyoxylate detoxification systems to avoid the formation of oxalate. Furthermore, this detoxification needs to be compartment‐specific since LDH is actively present in multiple subcellular compartments including peroxisomes, mitochondria, and the cytosol. Whereas the identity of these protection systems has been established for both peroxisomes and the cytosol as concluded from the deficiency of alanine glyoxylate aminotransferase (AGT) in primary hyperoxaluria type 1 (PH1) and glyoxylate reductase (GR) in PH2, the glyoxylate protection system in mitochondria has remained less well defined. In this manuscript, we show that the enzyme glyoxylate reductase has a bimodal distribution in human embryonic kidney (HEK293), hepatocellular carcinoma (HepG2), and cervical carcinoma (HeLa) cells and more importantly, in human liver, and is actively present in both the mitochondrial and cytosolic compartments. We conclude that the metabolism of glyoxylate in humans requires the complicated interaction between different subcellular compartments within the cell and discuss the implications for the different primary hyperoxalurias.</description><subject>Alcohol Oxidoreductases</subject><subject>Cervical carcinoma</subject><subject>Cytosol</subject><subject>Detoxification</subject><subject>Enzymes</subject><subject>glyoxylate metabolism</subject><subject>Glyoxylate reductase</subject><subject>Glyoxylates - metabolism</subject><subject>HEK293 Cells</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>hydroxyproline</subject><subject>Hyperoxaluria</subject><subject>L-Lactate dehydrogenase</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Mitochondria</subject><subject>Mitochondria, Liver - metabolism</subject><subject>oxalate</subject><subject>Oxalates - metabolism</subject><subject>peroxisomal disorders</subject><subject>Peroxisomes</subject><subject>Primary hyperoxaluria</subject><subject>Transaminases</subject><issn>0141-8955</issn><issn>1573-2665</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQhy1ERZfChQdAlrggRIon_pOEG2qhLSriAufIcSasV4kdbAe6Nx6BG-_Hk9TbLUXiwGk0mm8-zehHyBNgx8BY-Wpjp_4YygrgHlmBrHhRKiXvkxUDAUXdSHlIHsa4YYw1tZQPyCGvS8aUEivy62zc-qvtqBPSgP1iko74mp7iYJ1N9htS26NLdrBGJ-sdtY6ul0k7OuZhoJNN3qy964PVL6lNkdpp9iFpZ5AOPtC0Rmr8NOuQpiz6_eNnnNHsfLTH5K_-mv1Av9wd84gcDHqM-Pi2HpHP795-OjkvLj-eXZy8uSwMbzgUinf5V8Y6riVTaDpRd5o1Krecg-5AIOheDV0DgKIp60Ei9ggib5TCaH5Enu-9c_BfF4ypnWw0OI7aoV9iWzbAhagqYBl99g-68Utw-bpMyQqEkg3P1Is9ZYKPMeDQzsFOOmxbYO0urnYXV3sTV4af3iqXbsL-Dv2TTwZgD3y3I27_o2rfX3w43UuvATWipE0</recordid><startdate>202403</startdate><enddate>202403</enddate><creator>Garrelfs, Sander F.</creator><creator>Chornyi, Serhii</creator><creator>Brinke, Heleen</creator><creator>Ruiter, Jos</creator><creator>Groothoff, Jaap</creator><creator>Wanders, Ronald J. A.</creator><general>John Wiley & Sons, Inc</general><general>Blackwell Publishing Ltd</general><scope>24P</scope><scope>WIN</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>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6185-2616</orcidid></search><sort><creationdate>202403</creationdate><title>Glyoxylate reductase: Definitive identification in human liver mitochondria, its importance for the compartment‐specific detoxification of glyoxylate</title><author>Garrelfs, Sander F. ; Chornyi, Serhii ; Brinke, Heleen ; Ruiter, Jos ; Groothoff, Jaap ; Wanders, Ronald J. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3931-63b26600b3a506ecb48ba0963a5331ab14e1ad6fb911e4928f5eede140b324ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Alcohol Oxidoreductases</topic><topic>Cervical carcinoma</topic><topic>Cytosol</topic><topic>Detoxification</topic><topic>Enzymes</topic><topic>glyoxylate metabolism</topic><topic>Glyoxylate reductase</topic><topic>Glyoxylates - metabolism</topic><topic>HEK293 Cells</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>hydroxyproline</topic><topic>Hyperoxaluria</topic><topic>L-Lactate dehydrogenase</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Mitochondria</topic><topic>Mitochondria, Liver - metabolism</topic><topic>oxalate</topic><topic>Oxalates - metabolism</topic><topic>peroxisomal disorders</topic><topic>Peroxisomes</topic><topic>Primary hyperoxaluria</topic><topic>Transaminases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garrelfs, Sander F.</creatorcontrib><creatorcontrib>Chornyi, Serhii</creatorcontrib><creatorcontrib>Brinke, Heleen</creatorcontrib><creatorcontrib>Ruiter, Jos</creatorcontrib><creatorcontrib>Groothoff, Jaap</creatorcontrib><creatorcontrib>Wanders, Ronald J. A.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of inherited metabolic disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garrelfs, Sander F.</au><au>Chornyi, Serhii</au><au>Brinke, Heleen</au><au>Ruiter, Jos</au><au>Groothoff, Jaap</au><au>Wanders, Ronald J. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glyoxylate reductase: Definitive identification in human liver mitochondria, its importance for the compartment‐specific detoxification of glyoxylate</atitle><jtitle>Journal of inherited metabolic disease</jtitle><addtitle>J Inherit Metab Dis</addtitle><date>2024-03</date><risdate>2024</risdate><volume>47</volume><issue>2</issue><spage>280</spage><epage>288</epage><pages>280-288</pages><issn>0141-8955</issn><eissn>1573-2665</eissn><abstract>Glyoxylate is a key metabolite generated from various precursor substrates in different subcellular compartments including mitochondria, peroxisomes, and the cytosol. The fact that glyoxylate is a good substrate for the ubiquitously expressed enzyme lactate dehydrogenase (LDH) requires the presence of efficient glyoxylate detoxification systems to avoid the formation of oxalate. Furthermore, this detoxification needs to be compartment‐specific since LDH is actively present in multiple subcellular compartments including peroxisomes, mitochondria, and the cytosol. Whereas the identity of these protection systems has been established for both peroxisomes and the cytosol as concluded from the deficiency of alanine glyoxylate aminotransferase (AGT) in primary hyperoxaluria type 1 (PH1) and glyoxylate reductase (GR) in PH2, the glyoxylate protection system in mitochondria has remained less well defined. In this manuscript, we show that the enzyme glyoxylate reductase has a bimodal distribution in human embryonic kidney (HEK293), hepatocellular carcinoma (HepG2), and cervical carcinoma (HeLa) cells and more importantly, in human liver, and is actively present in both the mitochondrial and cytosolic compartments. We conclude that the metabolism of glyoxylate in humans requires the complicated interaction between different subcellular compartments within the cell and discuss the implications for the different primary hyperoxalurias.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>38200664</pmid><doi>10.1002/jimd.12711</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6185-2616</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0141-8955 |
| ispartof | Journal of inherited metabolic disease, 2024-03, Vol.47 (2), p.280-288 |
| issn | 0141-8955 1573-2665 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2913447710 |
| source | MEDLINE; Wiley Online Library All Journals |
| subjects | Alcohol Oxidoreductases Cervical carcinoma Cytosol Detoxification Enzymes glyoxylate metabolism Glyoxylate reductase Glyoxylates - metabolism HEK293 Cells Hepatocellular carcinoma Humans hydroxyproline Hyperoxaluria L-Lactate dehydrogenase Liver Liver - metabolism Mitochondria Mitochondria, Liver - metabolism oxalate Oxalates - metabolism peroxisomal disorders Peroxisomes Primary hyperoxaluria Transaminases |
| title | Glyoxylate reductase: Definitive identification in human liver mitochondria, its importance for the compartment‐specific detoxification of glyoxylate |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T22%3A25%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Glyoxylate%20reductase:%20Definitive%20identification%20in%20human%20liver%20mitochondria,%20its%20importance%20for%20the%20compartment%E2%80%90specific%20detoxification%20of%20glyoxylate&rft.jtitle=Journal%20of%20inherited%20metabolic%20disease&rft.au=Garrelfs,%20Sander%20F.&rft.date=2024-03&rft.volume=47&rft.issue=2&rft.spage=280&rft.epage=288&rft.pages=280-288&rft.issn=0141-8955&rft.eissn=1573-2665&rft_id=info:doi/10.1002/jimd.12711&rft_dat=%3Cproquest_cross%3E2913447710%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2957146593&rft_id=info:pmid/38200664&rfr_iscdi=true |