Creatine biosynthesis and transport in health and disease.

Autor: Joncquel-Chevalier Curt M; Biochemistry and Molecular Biology, Hormonology-Metabolism-Nutrition & Oncology (HMNO), Center of Biology & Pathology (CBP) Pierre-Marie Degand, CHRU Lille, 59037 Lille, France; RADEME Research Team for Rare Metabolic and Developmental Diseases, EA 7364, Université Lille 2, Lille, France., Voicu PM; Clinical Chemistry Laboratory, Dr Schaffner Hospital of Lens, 62307 Lens, France., Fontaine M; Biochemistry and Molecular Biology, Hormonology-Metabolism-Nutrition & Oncology (HMNO), Center of Biology & Pathology (CBP) Pierre-Marie Degand, CHRU Lille, 59037 Lille, France; RADEME Research Team for Rare Metabolic and Developmental Diseases, EA 7364, Université Lille 2, Lille, France., Dessein AF; Biochemistry and Molecular Biology, Hormonology-Metabolism-Nutrition & Oncology (HMNO), Center of Biology & Pathology (CBP) Pierre-Marie Degand, CHRU Lille, 59037 Lille, France., Porchet N; Biochemistry and Molecular Biology, Hormonology-Metabolism-Nutrition & Oncology (HMNO), Center of Biology & Pathology (CBP) Pierre-Marie Degand, CHRU Lille, 59037 Lille, France; Inserm, Lille, France., Mention-Mulliez K; RADEME Research Team for Rare Metabolic and Developmental Diseases, EA 7364, Université Lille 2, Lille, France; Medical Reference Center for Inherited Metabolic Diseases, Jeanne de Flandres Hospital, CHRU Lille, 59037 Lille, France., Dobbelaere D; RADEME Research Team for Rare Metabolic and Developmental Diseases, EA 7364, Université Lille 2, Lille, France; Medical Reference Center for Inherited Metabolic Diseases, Jeanne de Flandres Hospital, CHRU Lille, 59037 Lille, France., Soto-Ares G; Department of Neuroradiology, Roger Salengro Hospital, CHRU Lille, 59037 Lille, France., Cheillan D; Hospices Civils de Lyon, Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Groupement Hospitalier Est, 69677 Bron, France; Lyon University, INSERM U1060, CarMeN Laboratory, University Lyon-1, INSA-Lyon, F-69600 Oullins, France., Vamecq J; Biochemistry and Molecular Biology, Hormonology-Metabolism-Nutrition & Oncology (HMNO), Center of Biology & Pathology (CBP) Pierre-Marie Degand, CHRU Lille, 59037 Lille, France; RADEME Research Team for Rare Metabolic and Developmental Diseases, EA 7364, Université Lille 2, Lille, France; Inserm, Lille, France. Electronic address: joseph.vamecq@inserm.fr.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2015 Dec; Vol. 119, pp. 146-65. Date of Electronic Publication: 2015 Nov 02.
DOI: 10.1016/j.biochi.2015.10.022
Abstrakt: Creatine is physiologically provided equally by diet and by endogenous synthesis from arginine and glycine with successive involvements of arginine glycine amidinotransferase [AGAT] and guanidinoacetate methyl transferase [GAMT]. A specific plasma membrane transporter, creatine transporter [CRTR] (SLC6A8), further enables cells to incorporate creatine and through uptake of its precursor, guanidinoacetate, also directly contributes to creatine biosynthesis. Breakthrough in the role of creatine has arisen from studies on creatine deficiency disorders. Primary creatine disorders are inherited as autosomal recessive (mutations affecting GATM [for glycine-amidinotransferase, mitochondrial]) and GAMT genes) or X-linked (SLC6A8 gene) traits. They have highlighted the role of creatine in brain functions altered in patients (global developmental delay, intellectual disability, behavioral disorders). Creatine modulates GABAergic and glutamatergic cerebral pathways, presynaptic CRTR (SLC6A8) ensuring re-uptake of synaptic creatine. Secondary creatine disorders, addressing other genes, have stressed the extraordinary imbrication of creatine metabolism with many other cellular pathways. This high dependence on multiple pathways supports creatine as a cellular sensor, to cell methylation and energy status. Creatine biosynthesis consumes 40% of methyl groups produced as S-adenosylmethionine, and creatine uptake is controlled by AMP activated protein kinase, a ubiquitous sensor of energy depletion. Today, creatine is considered as a potential sensor of cell methylation and energy status, a neurotransmitter influencing key (GABAergic and glutamatergic) CNS neurotransmission, therapeutic agent with anaplerotic properties (towards creatine kinases [creatine-creatine phosphate cycle] and creatine neurotransmission), energetic and antioxidant compound (benefits in degenerative diseases through protection against energy depletion and oxidant species) with osmolyte behavior (retention of water by muscle). This review encompasses all these aspects by providing an illustrated metabolic account for brain and body creatine in health and disease, an algorithm to diagnose metabolic and gene bases of primary and secondary creatine deficiencies, and a metabolic exploration by (1)H-MRS assessment of cerebral creatine levels and response to therapeutic measures.
(Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
Databáze: MEDLINE
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