Polyunsaturated fatty acid desaturation is a mechanism for glycolytic NAD+ recycling
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Wondong | - |
dc.contributor.author | Deik, Amy | - |
dc.contributor.author | Gonzalez, Clicerio | - |
dc.contributor.author | Gonzalez, Maria Elena | - |
dc.contributor.author | Fu, Feifei | - |
dc.contributor.author | Ferrari, Michele | - |
dc.contributor.author | Churchhouse, Claire L. | - |
dc.contributor.author | Florez, Jose C. | - |
dc.contributor.author | Jacobs, Suzanne B.R. | - |
dc.contributor.author | Clish, Clary B. | - |
dc.contributor.author | Rhee, Eugene P. | - |
dc.date.accessioned | 2023-08-16T07:38:14Z | - |
dc.date.available | 2023-08-16T07:38:14Z | - |
dc.date.issued | 2019-04 | - |
dc.identifier.issn | 1550-4131 | - |
dc.identifier.issn | 1932-7420 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/113960 | - |
dc.description.abstract | The reactions catalyzed by the delta-5 and delta-6 desaturases (D5D/D6D), key enzymes responsible for highly unsaturated fatty acid (HUFA) synthesis, regenerate NAD + from NADH. Here, we show that D5D/D6D provide a mechanism for glycolytic NAD + recycling that permits ongoing glycolysis and cell viability when the cytosolic NAD + /NADH ratio is reduced, analogous to lactate fermentation. Although lesser in magnitude than lactate production, this desaturase-mediated NAD + recycling is acutely adaptive when aerobic respiration is impaired in vivo. Notably, inhibition of either HUFA synthesis or lactate fermentation increases the other, underscoring their interdependence. Consistent with this, a type 2 diabetes risk haplotype in SLC16A11 that reduces pyruvate transport (thus limiting lactate production) increases D5D/D6D activity in vitro and in humans, demonstrating a chronic effect of desaturase-mediated NAD + recycling. These findings highlight key biologic roles for D5D/D6D activity independent of their HUFA end products and expand the current paradigm of glycolytic NAD + regeneration. Kim et al. find that highly unsaturated fatty acid (HUFA) synthesis is a mechanism for glycolytic NAD + recycling, analogous to lactate fermentation. This finding highlights a key biologic role for lipid desaturation independent of HUFA end products and provides insight into genetic studies linking HUFA desaturation with human disease. © 2018 Elsevier Inc. | - |
dc.format.extent | 15 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Cell Press | - |
dc.title | Polyunsaturated fatty acid desaturation is a mechanism for glycolytic NAD+ recycling | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1016/j.cmet.2018.12.023 | - |
dc.identifier.scopusid | 2-s2.0-85063291423 | - |
dc.identifier.wosid | 000463015800010 | - |
dc.identifier.bibliographicCitation | Cell Metabolism, pp 856 - 870 | - |
dc.citation.title | Cell Metabolism | - |
dc.citation.startPage | 856 | - |
dc.citation.endPage | 870 | - |
dc.type.docType | 정기학술지(Article(Perspective Article포함)) | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.subject.keywordPlus | GENOME-WIDE ASSOCIATION | - |
dc.subject.keywordPlus | ALPHA-LINOLENIC ACID | - |
dc.subject.keywordPlus | LACTATE | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | DELTA-5 | - |
dc.subject.keywordPlus | LOCI | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | BIOSYNTHESIS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | CLONING | - |
dc.subject.keywordAuthor | delta-5-desaturase | - |
dc.subject.keywordAuthor | delta-6-desaturase | - |
dc.subject.keywordAuthor | FADS1-3 | - |
dc.subject.keywordAuthor | highly unsaturated fatty acids | - |
dc.subject.keywordAuthor | NAD + recycling | - |
dc.subject.keywordAuthor | polyunsaturated fatty acids | - |
dc.subject.keywordAuthor | SLC16A11 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S1550413118308064?pes=vor | - |
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