Elevation of cerebrospinal fluid choline levels by nicotinamide involves the enzymatic formation of N1-methylnicotinamide in brain tissue |
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| Affiliation: | 1. National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China;2. Analytical &Testing Center, Sichuan University, Chengdu 610041, China;1. Division of Gastroenterology, Hepatology and Nutrition, Children''s Hospital of Philadelphia, Philadelphia, PA, USA;2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;3. Department of Pathology and Laboratory Medicine, Children''s Hospital of Philadelphia, Philadelphia, Philadelphia, PA, USA;1. Department of Biochemistry, Memorial University of Newfoundland, St. John''s, NL, Canada A1B 3X9;2. Department of Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John''s, NL, Canada A1B 3V6;3. Diabetes & Nutritional Sciences Division, King''s College, London, United Kingdom SE1 9NH |
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| Abstract: | Nicotinamide administration can elevate plasma and brain choline levels and produce a marginal increase in striatal acetylcholine levels in the rat. We now report that subcutaneous nicotinamide produces a substantial and long-lasting rise in asternal cerebrospinal fluid (CSF) levels of choline in free-moving rats, possibly through the enzymatic formation of N1-methylnicotinamide (NMN) in brain. CSF choline levels peaked 2 hours after nicotinamide administration and were accompanied by increases in striatal, cortical, hippocampal and plasma choline levels. The enzymatic formation of [3H]NMN in rat brain was evaluated by incubating aliquots of rat brain cytosol with unlabelled nicotinamide and the methyl donor [3H]S-adenosylmethionine. High performance liquid chromatography and radiochemical detection demonstrated that [3H]NMN was specifically formed by a brain cytosolic enzyme. The production of [3H]NMN was dependent on exogenous nicotinamide and could be prevented by denaturing the cytosol. The metabolism of nicotinamide to NMN in rat brain may explain the rise in CSF choline levels since NMN, a quaternary amine, can inhibit choline transport at the choroid villus and reduce choline clearance. |
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