title: Structural correlates of the creatine transporter function regulation: the undiscovered country.
abstract: Creatine (Cr) and phosphocreatine constitute an energy shuttle that links ATP production in mitochondria to subcellular locations of ATP consumption. Cells in tissues that are reliant on this energy shuttle, such as myocytes and neurons, appear to have very limited ability to synthesize creatine. Therefore, these cells depend on Cr uptake across the cell membrane by a specialized creatine transporter (CrT solute carrier SLC6A8) in order to maintain intracellular creatine levels. Cr supplementation has been shown to have a beneficial effect in numerous in vitro and in vivo models, particularly in cases of oxidative stress, and is also widely used by athletes as a performance enhancement nutraceutical. Intracellular creatine content is maintained within narrow limits. However, the physiological and cellular mechanisms that mediate Cr transport during health and disease (such as cardiac failure) are not understood. In this narrative mini-review, we summarize the last three decades of research on CrT structure, function and regulation.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas, Medical Branch, 301 University Boulevard, Galveston, TX, USA. lasantac@utmb.edu.
authors.forename: Lucia
authors.identifier: 0000-0002-7525-1782
authors.initials: L
authors.lastname: Santacruz
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas, Medical Branch, 301 University Boulevard, Galveston, TX, USA.|Departament of Surgery and the institute for Translational Sciences, University of Texas, Medical Branch, Galveston, USA.
authors.forename: Danny O
authors.initials: DO
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D003401:Creatine / Q000378:metabolism*; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D032342:Muscle Cells / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D009419:Nerve Tissue Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C094770:SLC6A8 protein, human; D003401:Creatine
keywords: Creatine; Creatine transport; Energy metabolism; Membrane transporter modulation