Lipid synthesis in protozoan parasites: A comparison between kinetoplastids and apicomplexans
Lipid metabolism is of crucial importance for pathogens. Lipids serve as cellular building blocks, signalling molecules, energy stores, posttranslational modifiers, and pathogenesis factors. Parasites rely on a complex system of uptake and synthesis mechanisms to satisfy their lipid needs. The param...
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Veröffentlicht in: | Progress in lipid research 2013-10, Vol.52 (4), p.488-512 |
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description | Lipid metabolism is of crucial importance for pathogens. Lipids serve as cellular building blocks, signalling molecules, energy stores, posttranslational modifiers, and pathogenesis factors. Parasites rely on a complex system of uptake and synthesis mechanisms to satisfy their lipid needs. The parameters of this system change dramatically as the parasite transits through the various stages of its life cycle. Here we discuss the tremendous recent advances that have been made in the understanding of the synthesis and uptake pathways for fatty acids and phospholipids in apicomplexan and kinetoplastid parasites, including Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma and Leishmania. Lipid synthesis differs in significant ways between parasites from both phyla and the human host. Parasites have acquired novel pathways through endosymbiosis, as in the case of the apicoplast, have dramatically reshaped substrate and product profiles, and have evolved specialized lipids to interact with or manipulate the host. These differences potentially provide opportunities for drug development. We outline the lipid pathways for key species in detail as they progress through the developmental cycle and highlight those that are of particular importance to the biology of the pathogens and/or are the most promising targets for parasite-specific treatment. |
doi_str_mv | 10.1016/j.plipres.2013.06.003 |
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Lipids serve as cellular building blocks, signalling molecules, energy stores, posttranslational modifiers, and pathogenesis factors. Parasites rely on a complex system of uptake and synthesis mechanisms to satisfy their lipid needs. The parameters of this system change dramatically as the parasite transits through the various stages of its life cycle. Here we discuss the tremendous recent advances that have been made in the understanding of the synthesis and uptake pathways for fatty acids and phospholipids in apicomplexan and kinetoplastid parasites, including Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma and Leishmania. Lipid synthesis differs in significant ways between parasites from both phyla and the human host. Parasites have acquired novel pathways through endosymbiosis, as in the case of the apicoplast, have dramatically reshaped substrate and product profiles, and have evolved specialized lipids to interact with or manipulate the host. These differences potentially provide opportunities for drug development. We outline the lipid pathways for key species in detail as they progress through the developmental cycle and highlight those that are of particular importance to the biology of the pathogens and/or are the most promising targets for parasite-specific treatment.</description><identifier>ISSN: 0163-7827</identifier><identifier>EISSN: 1873-2194</identifier><identifier>DOI: 10.1016/j.plipres.2013.06.003</identifier><identifier>PMID: 23827884</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Acetyltransferases - antagonists & inhibitors ; Acetyltransferases - metabolism ; Animals ; Apicomplexa ; Apicomplexa - enzymology ; Apicomplexa - metabolism ; Drugs ; Fatty Acid Synthase, Type II - antagonists & inhibitors ; Fatty Acid Synthase, Type II - metabolism ; Fatty acid synthesis ; Fatty Acids - metabolism ; Fatty Acids, Unsaturated - metabolism ; Kinetoplastida ; Kinetoplastida - enzymology ; Kinetoplastida - metabolism ; Lipid Metabolism - physiology ; Phospholipid synthesis ; Phospholipids - metabolism ; Protozoa</subject><ispartof>Progress in lipid research, 2013-10, Vol.52 (4), p.488-512</ispartof><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><rights>2013 Elsevier Ltd. All rights reserved. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-e4a83cf239af65bb7095cc8030ea7a4f3d03a57ff279a2bce0d917790089f03c3</citedby><cites>FETCH-LOGICAL-c533t-e4a83cf239af65bb7095cc8030ea7a4f3d03a57ff279a2bce0d917790089f03c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.plipres.2013.06.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23827884$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramakrishnan, Srinivasan</creatorcontrib><creatorcontrib>Serricchio, Mauro</creatorcontrib><creatorcontrib>Striepen, Boris</creatorcontrib><creatorcontrib>Bütikofer, Peter</creatorcontrib><title>Lipid synthesis in protozoan parasites: A comparison between kinetoplastids and apicomplexans</title><title>Progress in lipid research</title><addtitle>Prog Lipid Res</addtitle><description>Lipid metabolism is of crucial importance for pathogens. Lipids serve as cellular building blocks, signalling molecules, energy stores, posttranslational modifiers, and pathogenesis factors. Parasites rely on a complex system of uptake and synthesis mechanisms to satisfy their lipid needs. The parameters of this system change dramatically as the parasite transits through the various stages of its life cycle. Here we discuss the tremendous recent advances that have been made in the understanding of the synthesis and uptake pathways for fatty acids and phospholipids in apicomplexan and kinetoplastid parasites, including Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma and Leishmania. Lipid synthesis differs in significant ways between parasites from both phyla and the human host. Parasites have acquired novel pathways through endosymbiosis, as in the case of the apicoplast, have dramatically reshaped substrate and product profiles, and have evolved specialized lipids to interact with or manipulate the host. These differences potentially provide opportunities for drug development. We outline the lipid pathways for key species in detail as they progress through the developmental cycle and highlight those that are of particular importance to the biology of the pathogens and/or are the most promising targets for parasite-specific treatment.</description><subject>Acetyltransferases - antagonists & inhibitors</subject><subject>Acetyltransferases - metabolism</subject><subject>Animals</subject><subject>Apicomplexa</subject><subject>Apicomplexa - enzymology</subject><subject>Apicomplexa - metabolism</subject><subject>Drugs</subject><subject>Fatty Acid Synthase, Type II - antagonists & inhibitors</subject><subject>Fatty Acid Synthase, Type II - metabolism</subject><subject>Fatty acid synthesis</subject><subject>Fatty Acids - metabolism</subject><subject>Fatty Acids, Unsaturated - metabolism</subject><subject>Kinetoplastida</subject><subject>Kinetoplastida - enzymology</subject><subject>Kinetoplastida - metabolism</subject><subject>Lipid Metabolism - physiology</subject><subject>Phospholipid synthesis</subject><subject>Phospholipids - metabolism</subject><subject>Protozoa</subject><issn>0163-7827</issn><issn>1873-2194</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERbeFnwDKkUvC2M6HwwFUVbQgrcQFjshynAn1krWDx1tof3292qWCEyfb42fesfww9pJDxYG3bzbVMrslIlUCuKygrQDkE7biqpOl4H39lK0yJ8tOie6UnRFtAKBRgj9jp0LmolL1in1bu8WNBd35dIPkqHC-WGJI4T6YvDPRkEtIb4uLwoZtPjsKvhgw_UL0xQ_nMYVlNpTcSIXxY2EWtwdn_G08PWcnk5kJXxzXc_b16sOXy4_l-vP1p8uLdWkbKVOJtVHSTkL2ZmqbYeigb6xVIAFNZ-pJjiBN002T6HojBosw9rzregDVTyCtPGfvDrnLbtjiaNGnaGa9RLc18U4H4_S_N97d6O_hVksloa1lDnh9DIjh5w4p6a0ji_NsPIYdaV43qgHRK5HR5oDaGIgiTo9jOOi9Gr3RRzV6r0ZDq7Oa3Pfq7zc-dv1xkYH3BwDzT906jJqsQ29xdBFt0mNw_xnxAHrJpio</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Ramakrishnan, Srinivasan</creator><creator>Serricchio, Mauro</creator><creator>Striepen, Boris</creator><creator>Bütikofer, Peter</creator><general>Elsevier Ltd</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20131001</creationdate><title>Lipid synthesis in protozoan parasites: A comparison between kinetoplastids and apicomplexans</title><author>Ramakrishnan, Srinivasan ; Serricchio, Mauro ; Striepen, Boris ; Bütikofer, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-e4a83cf239af65bb7095cc8030ea7a4f3d03a57ff279a2bce0d917790089f03c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetyltransferases - antagonists & inhibitors</topic><topic>Acetyltransferases - metabolism</topic><topic>Animals</topic><topic>Apicomplexa</topic><topic>Apicomplexa - enzymology</topic><topic>Apicomplexa - metabolism</topic><topic>Drugs</topic><topic>Fatty Acid Synthase, Type II - antagonists & inhibitors</topic><topic>Fatty Acid Synthase, Type II - metabolism</topic><topic>Fatty acid synthesis</topic><topic>Fatty Acids - metabolism</topic><topic>Fatty Acids, Unsaturated - metabolism</topic><topic>Kinetoplastida</topic><topic>Kinetoplastida - enzymology</topic><topic>Kinetoplastida - metabolism</topic><topic>Lipid Metabolism - physiology</topic><topic>Phospholipid synthesis</topic><topic>Phospholipids - metabolism</topic><topic>Protozoa</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ramakrishnan, Srinivasan</creatorcontrib><creatorcontrib>Serricchio, Mauro</creatorcontrib><creatorcontrib>Striepen, Boris</creatorcontrib><creatorcontrib>Bütikofer, Peter</creatorcontrib><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>Progress in lipid research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ramakrishnan, Srinivasan</au><au>Serricchio, Mauro</au><au>Striepen, Boris</au><au>Bütikofer, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lipid synthesis in protozoan parasites: A comparison between kinetoplastids and apicomplexans</atitle><jtitle>Progress in lipid research</jtitle><addtitle>Prog Lipid Res</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>52</volume><issue>4</issue><spage>488</spage><epage>512</epage><pages>488-512</pages><issn>0163-7827</issn><eissn>1873-2194</eissn><abstract>Lipid metabolism is of crucial importance for pathogens. Lipids serve as cellular building blocks, signalling molecules, energy stores, posttranslational modifiers, and pathogenesis factors. Parasites rely on a complex system of uptake and synthesis mechanisms to satisfy their lipid needs. The parameters of this system change dramatically as the parasite transits through the various stages of its life cycle. Here we discuss the tremendous recent advances that have been made in the understanding of the synthesis and uptake pathways for fatty acids and phospholipids in apicomplexan and kinetoplastid parasites, including Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma and Leishmania. Lipid synthesis differs in significant ways between parasites from both phyla and the human host. Parasites have acquired novel pathways through endosymbiosis, as in the case of the apicoplast, have dramatically reshaped substrate and product profiles, and have evolved specialized lipids to interact with or manipulate the host. 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subjects | Acetyltransferases - antagonists & inhibitors Acetyltransferases - metabolism Animals Apicomplexa Apicomplexa - enzymology Apicomplexa - metabolism Drugs Fatty Acid Synthase, Type II - antagonists & inhibitors Fatty Acid Synthase, Type II - metabolism Fatty acid synthesis Fatty Acids - metabolism Fatty Acids, Unsaturated - metabolism Kinetoplastida Kinetoplastida - enzymology Kinetoplastida - metabolism Lipid Metabolism - physiology Phospholipid synthesis Phospholipids - metabolism Protozoa |
title | Lipid synthesis in protozoan parasites: A comparison between kinetoplastids and apicomplexans |
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