{"doi":"10.1016/j.jlr.2025.100945","title":"Determination of FAT-1 desaturase activity and substrate preference","abstract":"n-3 PUFAs possess numerous health benefits. The FAT-1 desaturase in the model organism Caenorhabditis elegans is a Δ15-desaturase that converts n-6 PUFAs into n-3 PUFAs. Transgenic expression of FAT-1 has been used in organisms, such as pigs, mice, and fish, to improve n-3 PUFA levels. However, the determination of FAT-1 activity and substrate preference per se remains unclear. AlphaFold structure prediction revealed that FAT-1 is an integral membrane protein located in the endoplasmic reticulum, and it consists of four transmembrane helices (1-4) with a functional CYTB5 domain in the N terminus and a desaturase domain containing three histidine-rich sequences (His boxes) in the C terminus. A small region in the desaturase domain containing amino acids 210-217, especially G212, G216, and S217, is essential for its activity. FAT-1 can convert all four n-6 PUFAs to corresponding or downstream n-3 PUFAs in both C. elegans and mammalian cells and may prioritize the conversion of C20:4n6 (arachidonic acid) to C20:5n3 (EPA). These results uncover the significant mechanism of the activity and substrate preference of the FAT-1 desaturase, providing insights into the transgenic application of FAT-1.","journal":"Journal of Lipid Research","year":2025,"id":581450,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":43196,"name":"Yanli Wang","orcid":"0000-0001-7438-5001","position":1,"is_corresponding":false},{"id":1492685,"name":"Yao Xu","orcid":"0000-0002-6366-4053","position":2,"is_corresponding":false},{"id":1492686,"name":"Yuan Yao","orcid":"0009-0001-6817-3907","position":3,"is_corresponding":false},{"id":1492687,"name":"Lin Fu","orcid":"0000-0003-1069-3560","position":4,"is_corresponding":false},{"id":1492688,"name":"Shaomei He","orcid":"0000-0002-9547-4107","position":5,"is_corresponding":false},{"id":16311,"name":"Jing Leng","orcid":"0000-0001-6115-2153","position":6,"is_corresponding":false},{"id":727470,"name":"Qun Lu","orcid":"0000-0003-3761-4236","position":7,"is_corresponding":false},{"id":168277,"name":"Xiaoju Zou","orcid":null,"position":8,"is_corresponding":false},{"id":1492689,"name":"Bin Liang","orcid":"0000-0001-9131-5478","position":9,"is_corresponding":false},{"id":836209,"name":"Xiumei Xu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:58:47.357782Z","pmid":"41242696","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}