title: Metabolism of Mannose in Cultured Primary Rat Neurons.
abstract: Glucose is the main peripheral substrate for energy production in the brain. However, as other hexoses are present in blood and cerebrospinal fluid, we have investigated whether neurons have the potential to metabolize, in addition to glucose, also the hexoses mannose, fructose or galactose. Incubation of primary cerebellar granule neurons in the absence of glucose caused severe cell toxicity within 24 h, which could not be prevented by application of galactose or fructose, while the cells remained viable during incubation in the presence of either mannose or glucose. In addition, cultured neurons produced substantial and almost identical amounts of lactate after exposure to either glucose or mannose, while lactate production was low in the presence of fructose and hardly detectable during incubations without hexoses or with galactose as carbon source. Determination of the KMvalues of hexokinase in lysates of cultured neurons for the hexoses revealed values in the micromolar range for mannose (32 ± 2 µM) and glucose (59 ± 10 µM) and in the millimolar range for fructose (4.4 ± 2.3 mM), demonstrating that mannose is efficiently phosphorylated by neuronal hexokinase. Finally, cultured neurons contained reasonable specific activity of the enzyme phosphomannose isomerase, which is required for isomerization of the hexokinase product mannose-6-phosphate into the glycolysis intermediate fructose-6-phosphate. These data demonstrate that cultured cerebellar granule neurons have the potential and express the required enzymes to efficiently metabolize mannose, while galactose and fructose serve at best poorly as extracellular carbon sources for neurons.
authors.affiliation: Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany.|Centre for Environmental Research and Sustainable Technology, University of Bremen, Bremen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Rastedt
authors.affiliation: Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany.|Centre for Environmental Research and Sustainable Technology, University of Bremen, Bremen, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Blumrich
authors.affiliation: Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany. dringen@uni-bremen.de.|Centre for Environmental Research and Sustainable Technology, University of Bremen, Bremen, Germany. dringen@uni-bremen.de.
authors.forename: Ralf
authors.identifier: http://orcid.org/0000-0001-7869-1305
authors.initials: R
authors.lastname: Dringen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008358:Mannose
keywords: Fructose; Glucose; Hexokinase; Isomerases; Mannose; Neurons