Your browser doesn't support javascript.
loading
A PTER-dependent pathway of taurine metabolism linked to energy balance.
Wei, Wei; Lyu, Xuchao; Markhard, Andrew L; Fu, Sipei; Mardjuki, Rachel E; Cavanagh, Peter E; Zeng, Xianfeng; Rajniak, Jakub; Lu, Nannan; Xiao, Shuke; Zhao, Meng; Moya-Garzon, Maria Dolores; Truong, Steven D; Chou, Jonathan Chiu-Chun; Wat, Lianna W; Chidambaranathan-Reghupaty, Saranya; Coassolo, Laetitia; Xu, Duo; Shen, Fangfang; Huang, Wentao; Ramirez, Cuauhtemoc B; Jang, Cholsoon; Svensson, Katrin J; Fischbach, Michael A; Long, Jonathan Z.
Afiliação
  • Wei W; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Lyu X; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Markhard AL; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Fu S; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Mardjuki RE; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA.
  • Cavanagh PE; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Zeng X; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Rajniak J; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Lu N; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Xiao S; Department of Biology, Stanford University, Stanford, CA, USA.
  • Zhao M; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Moya-Garzon MD; Department of Biochemistry, Stanford University, Stanford, CA, USA.
  • Truong SD; Department of Chemistry, Stanford University, Stanford, CA, USA.
  • Chou JC; Department of Biochemistry, Stanford University, Stanford, CA, USA.
  • Wat LW; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Chidambaranathan-Reghupaty S; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Coassolo L; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Xu D; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Shen F; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
  • Huang W; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Ramirez CB; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Jang C; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Svensson KJ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Fischbach MA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.
  • Long JZ; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
bioRxiv ; 2024 Mar 22.
Article em En | MEDLINE | ID: mdl-38562797
ABSTRACT
Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. 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 metabolites4,5. One such taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by diverse physiologic perturbations that alter taurine and/or acetate flux, including endurance exercise7, nutritional taurine supplementation8, and alcohol consumption6,9. While taurine N-acetyltransferase activity has been previously detected in mammalian cells6,7, 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.
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article