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 Guloâ??/â?? 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 2â??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.
Content Type Journal Article
Pages 1-9
DOI 10.1007/s10858-011-9485-5
Authors
Gavin E. Duggan, Biochemistry Research Group, Department of Biological Sciences, University of Calgary, 2500 University Drive N.W, Calgary, AB T2N 1N4, Canada
B. Joan Miller, Department of Biochemistry and Molecular Biology, The McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB T2N 4N1, Canada
Frank R. Jirik, Department of Biochemistry and Molecular Biology, The McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB T2N 4N1, Canada
Hans J. Vogel, Biochemistry Research Group, Department of Biological Sciences, University of Calgary, 2500 University Drive N.W, Calgary, AB T2N 1N4, Canada
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Metabolic profiling of vitamin C deficiency in Guloâ??/â?? mice using proton NMR spectroscopy
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