title: Metabolic profiling of vitamin C deficiency in Gulo-/- mice using proton NMR spectroscopy.
abstract: Nutrient deficiencies are an ongoing problem in many populations and ascorbic acid is a key vitamin whose mild or acute absence leads to a number of conditions including the famously debilitating scurvy. As such, the biochemical effects of ascorbate deficiency merit ongoing scrutiny, and the Gulo knockout mouse provides a useful model for the metabolomic examination of vitamin C deficiency. Like humans, these animals are incapable of synthesizing ascorbic acid but with dietary supplements are otherwise healthy and grow normally. In this study, all vitamin C sources were removed after weaning from the diet of Gulo-/- mice (n = 7) and wild type controls (n = 7) for 12 weeks before collection of serum. A replicate study was performed with similar parameters but animals were harvested pre-symptomatically after 2-3 weeks. The serum concentration of 50 metabolites was determined by quantitative profiling of 1D proton NMR spectra. Multivariate statistical models were used to describe metabolic changes as compared to control animals; replicate study animals were used for external validation of the resulting models. The results of the study highlight the metabolites and pathways known to require ascorbate for proper flux.
authors.affiliation: Biochemistry Research Group, Department of Biological Sciences, University of Calgary, 2500 University Drive N.W, Calgary, AB, T2N 1N4, Canada.
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Duggan
authors.forename: B
authors.initials: B
authors.lastname: Joan Miller
authors.forename: Frank R
authors.initials: FR
authors.lastname: Jirik
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001206:Ascorbic Acid Deficiency / Q000378:metabolism*; D050544:L-Gulonolactone Oxidase / Q000172:deficiency / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D051379:Mice; D018345:Mice, Knockout
chemical_list: D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid