title: Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS.
abstract: Citrate is key constituent of the tricarboxylic acid (TCA) cycle, serves as substrate for fatty acid and sterol biosynthesis, and functions as a key regulator of intermediary energy metabolism. Ursula Sonnewald had initiated studies using for the first time both proton- and13C-NMR to investigate metabolic processes in cultured neurons and astrocytes resulting in the important observation that citrate was specifically synthesized in and released from astrocytes in large amounts which is in keeping with the high concentration found in the CSF. The aim of this review is to highlight the possible roles of citrate in physiological and pathophysiological processes in the CNS. An interesting feature of citrate is its ability to chelate Ca2+, Mg2+and Zn2+and thereby playing a pivotal role as an endogenous modulator of glutamate receptors and in particular the NMDA subtypes of these receptors in the CNS. Besides its presence in cerebrospinal fluid (CSF) citrate is also found in high amounts in prostate fluid reaching concentrations as high as 180 mM and here Zn2+seems also to play an important role, which makes prostate cells interesting for comparison of features of citrate and Zn2+between these cells and cells in the CNS.
authors.affiliation: Biopeople, Denmark's Life Science Cluster, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark. niels.westergaard@biopeople.ku.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Westergaard
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors.forename: Helle S
authors.initials: HS
authors.lastname: Waagepetersen
authors.affiliation: Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark.
authors.forename: Bo
authors.initials: B
authors.lastname: Belhage
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Schousboe
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D019343:Citric Acid / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D019343:Citric Acid; D008274:Magnesium; D015032:Zinc
keywords: Astrocytes; Citrate metabolism; NMDA-receptor; NMR-spectroscopy; Neurons; Zinc