title: Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: down-regulation of the expression of creatine transporter isoforms in skeletal muscle.
abstract: Interest in creatine (Cr) as a nutritional supplement and ergogenic aid for athletes has surged over recent years. After cellular uptake, Cr is phosphorylated to phosphocreatine (PCr) by the creatine kinase (CK) reaction using ATP. At subcellular sites with high energy requirements, e.g. at the myofibrillar apparatus during muscle contraction, CK catalyzes the transphosphorylation of PCr to ADP to regenerate ATP, thus preventing a depletion of ATP levels. PCr is thus available as an immediate energy source, serving not only as an energy buffer but also as an energy transport vehicle. Ingestion of creatine increases intramuscular Cr, as well as PCr concentrations, and leads to exercise enhancement, especially in sprint performance. Additional benefits of Cr supplementation have also been noticed for high-intensity long-endurance tasks, e.g. shortening of recovery periods after physical exercise. The present article summarizes recent findings on the influence of Cr supplementation on energy metabolism, and introduces the Cr transporter protein (CreaT), responsible for uptake of Cr into cells, as one of the key-players for the multi-faceted regulation of cellular Cr homeostasis. Furthermore, it is suggested that patients with disturbances in Cr metabolism or with different neuro-muscular diseases may benefit from Cr supplementation as an adjuvant therapy to relieve or delay the onset of symptoms. Although it is still unclear how Cr biosynthesis and transport are regulated in health and disease, so far there are no reports of harmful side effects of Cr loading in humans. However, in this study, we report that chronic Cr supplementation in rats down-regulates in vivo the expression of the CreaT. In addition, we describe the presence of CreaT isoforms most likely generated by alternative splicing.
authors.affiliation: Institute for Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, Zürich.
authors.forename: M L
authors.initials: ML
authors.lastname: Guerrero-Ontiveros
authors.forename: T
authors.initials: T
authors.lastname: Wallimann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D003401:Creatine / Q000494:pharmacology* / Q000627:therapeutic use; D019587:Dietary Supplements; D015536:Down-Regulation / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D015444:Exercise / Q000502:physiology; D006801:Humans; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000502:physiology*; D009468:Neuromuscular Diseases / Q000628:therapy; D010725:Phosphocreatine / Q000502:physiology; D051381:Rats; D013177:Sports / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D009124:Muscle Proteins; C080679:creatine transporter; D010725:Phosphocreatine; D003401:Creatine