PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity.

Autor: Wei W; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Lyu X; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA., Markhard AL; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Fu S; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Department of Biology, Stanford University, Stanford, CA, USA., Mardjuki RE; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Department of Biochemistry, Stanford University, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA., Cavanagh PE; Department of Biochemistry, Stanford University, Stanford, CA, USA., Zeng X; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Department of Bioengineering, Stanford University, Stanford, CA, USA., Rajniak J; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Department of Bioengineering, Stanford University, Stanford, CA, USA., Lu N; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA., Xiao S; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Zhao M; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA., Moya-Garzon MD; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA., Truong SD; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Chou JC; Department of Chemistry, Stanford University, Stanford, CA, USA., Wat LW; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA., Chidambaranathan-Reghupaty S; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA., Coassolo L; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA., Xu D; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Department of Biochemistry, Stanford University, Stanford, CA, USA., Shen F; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA., Huang W; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Ramirez CB; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA., Jang C; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA., Li L; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Department of Biochemistry, Stanford University, Stanford, CA, USA.; Arc Institute, Palo Alto, CA, USA., Svensson KJ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA., Fischbach MA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Department of Bioengineering, Stanford University, Stanford, CA, USA., Long JZ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. jzlong@stanford.edu.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA. jzlong@stanford.edu.; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA. jzlong@stanford.edu.; The Phil and Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Sep; Vol. 633 (8028), pp. 182-188. Date of Electronic Publication: 2024 Aug 07.
DOI: 10.1038/s41586-024-07801-6
Abstrakt: 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 the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites 4,5 . One taurine metabolite is N-acetyltaurine 6 . Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise 7 , dietary taurine supplementation 8 and alcohol consumption 6,9 . So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the body mass index associated orphan enzyme phosphotriesterase-related (PTER) 10 is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.
(© 2024. The Author(s).)
Databáze: MEDLINE
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