{"doi":"10.1101/2024.03.21.586194","title":"A PTER-dependent pathway of taurine metabolism linked to energy balance","abstract":"Summary Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans 1–3 . In endogenous taurine metabolism, dedicated enzymes are involved in biosynthesis of taurine from cysteine as well as the downstream derivatization of taurine into secondary taurine metabolites 4,5 . One such taurine metabolite is N-acetyltaurine 6 . Levels of N-acetyltaurine are dynamically regulated by diverse physiologic perturbations that alter taurine and/or acetate flux, including endurance exercise 7 , nutritional taurine supplementation 8 , and alcohol consumption 6,9 . While taurine N-acetyltransferase activity has been previously detected in mammalian cells 6,7 , the molecular identity of this enzyme, and the physiologic relevance of N-acetyltaurine, have remained unknown. Here we show that the orphan body mass index-associated enzyme PTER (phosphotriesterase-related) 10 is the principal mammalian taurine N-acetyltransferase/hydrolase. In vitro, recombinant PTER catalyzes bidirectional taurine N-acetylation with free acetate as well as the reverse N-acetyltaurine hydrolysis reaction. Genetic ablation of PTER in mice results in complete loss of tissue taurine N-acetyltransferase/hydrolysis activities and systemic elevation of N-acetyltaurine levels. Upon stimuli that increase taurine levels, PTER-KO mice exhibit lower body weight, reduced adiposity, and improved glucose homeostasis. These phenotypes are recapitulated by administration of N-acetyltaurine to wild-type mice. Lastly, the anorexigenic and anti-obesity effects of N-acetyltaurine require functional GFRAL receptors. Together, these data uncover enzymatic control of a previously enigmatic pathway of secondary taurine metabolism linked to energy balance.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488158,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":766528,"name":"Xuchao Lyu","orcid":null,"position":1,"is_corresponding":false},{"id":243897,"name":"Andrew L. Markhard","orcid":null,"position":2,"is_corresponding":false},{"id":443906,"name":"Sipei Fu","orcid":"0000-0003-4967-2185","position":3,"is_corresponding":false},{"id":252621,"name":"Rachel E. Mardjuki","orcid":null,"position":4,"is_corresponding":false},{"id":615282,"name":"P. Cavanagh","orcid":"0000-0003-3146-664X","position":5,"is_corresponding":false},{"id":235553,"name":"Xianfeng Zeng","orcid":"0000-0001-9593-3388","position":6,"is_corresponding":false},{"id":791106,"name":"Jakub Rajniak","orcid":"0000-0003-2124-0647","position":7,"is_corresponding":false},{"id":1332629,"name":"Nannan Lu","orcid":"0000-0003-0905-8199","position":8,"is_corresponding":false},{"id":1202658,"name":"Shuke Xiao","orcid":"0000-0003-2103-128X","position":9,"is_corresponding":false},{"id":348821,"name":"Meng Zhao","orcid":"0000-0002-5415-8335","position":10,"is_corresponding":false},{"id":848531,"name":"María Dolores Moya-Garzón","orcid":"0000-0001-7212-9880","position":11,"is_corresponding":false},{"id":1332630,"name":"Steven Truong","orcid":"0000-0001-9624-4461","position":12,"is_corresponding":false},{"id":796288,"name":"Jonathan Chiu‐Chun Chou","orcid":"0009-0003-6840-8352","position":13,"is_corresponding":false},{"id":258263,"name":"Lianna W. Wat","orcid":"0000-0001-6998-0594","position":14,"is_corresponding":false},{"id":911168,"name":"Saranya Chidambaranathan Reghupaty","orcid":"0000-0001-6660-1296","position":15,"is_corresponding":false},{"id":920870,"name":"Laetitia Coassolo","orcid":"0000-0003-2138-4819","position":16,"is_corresponding":false},{"id":499067,"name":"Duo Xu","orcid":"0000-0003-0483-8719","position":17,"is_corresponding":false},{"id":992470,"name":"Fangfang Shen","orcid":"0000-0002-2989-6440","position":18,"is_corresponding":false},{"id":851335,"name":"Wentao Huang","orcid":"0000-0003-2921-8524","position":19,"is_corresponding":false},{"id":1005721,"name":"Cuauhtemoc B. Ramirez","orcid":"0000-0001-7182-1859","position":20,"is_corresponding":false},{"id":225539,"name":"Cholsoon Jang","orcid":"0000-0001-6651-4213","position":21,"is_corresponding":false},{"id":348824,"name":"Katrin J. Svensson","orcid":"0000-0001-5376-5128","position":22,"is_corresponding":false},{"id":44570,"name":"Michael A. Fischbach","orcid":"0000-0003-3079-8247","position":23,"is_corresponding":false},{"id":259637,"name":"Jonathan Z. Long","orcid":"0000-0003-2631-7463","position":24,"is_corresponding":false},{"id":259632,"name":"Wei Wei","orcid":"0000-0001-8110-0705","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T02:08:15.008850Z","pmid":"38562797","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":[]}