title: Glycine conjugation: importance in metabolism, the role of glycine N-acyltransferase, and factors that influence interindividual variation.
abstract: BACKGROUND
  Glycine conjugation of mitochondrial acyl-CoAs, catalyzed by glycine N-acyltransferase (GLYAT, E.C. 2.3.1.13), is an important metabolic pathway responsible for maintaining adequate levels of free coenzyme A (CoASH). However, because of the small number of pharmaceutical drugs that are conjugated to glycine, the pathway has not yet been characterized in detail. Here, we review the causes and possible consequences of interindividual variation in the glycine conjugation pathway.
  
  
  METHODS
  The authors review the importance of CoASH in metabolism, formation and toxicity of xenobiotic acyl-CoAs, and mechanisms for restoring levels of CoASH. They focus on GLYAT, glycine conjugation, how genetic variation in the GLYAT gene could influence glycine conjugation, and the emerging roles of glycine metabolism in cancer and musculoskeletal development.
  
  
  CONCLUSIONS
  The substrate selectivity of GLYAT and its variants needs to be further characterized, as organic acids can be toxic if the corresponding acyl-CoA is not a substrate for glycine conjugation. GLYAT activity affects mitochondrial ATP production, glycine availability, CoASH availability, and the toxicity of various organic acids. Therefore, variation in the glycine conjugation pathway could influence liver cancer, musculoskeletal development, and mitochondrial energy metabolism.
authors: North-West University, Centre for Human Metabonomics, Biochemistry Department, Potchefstroom, 2520, South Africa.
authors: Christoffel Petrus Stephanus
authors: CP
authors: Badenhorst
authors: Rencia
authors: R
authors: van der Sluis
authors: Elardus
authors: E
authors: Erasmus
authors: Alberdina Aike
authors: AA
authors: van Dijk
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D003065:Coenzyme A / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D006505:Hepatitis / Q000235:genetics / Q000473:pathology; D006801:Humans; D062385:Hydroxybenzoates / Q000378:metabolism / Q000633:toxicity; D008658:Inactivation, Metabolic; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D041641:Musculoskeletal Development / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D062385:Hydroxybenzoates; D015262:Xenobiotics; D000217:Acyltransferases; C020680:glycine acyltransferase; D003065:Coenzyme A; D005998:Glycine