title: In silico evidence for gluconeogenesis from fatty acids in humans.
abstract: The question whether fatty acids can be converted into glucose in humans has a long standing tradition in biochemistry, and the expected answer is "No". Using recent advances in Systems Biology in the form of large-scale metabolic reconstructions, we reassessed this question by performing a global investigation of a genome-scale human metabolic network, which had been reconstructed on the basis of experimental results. By elementary flux pattern analysis, we found numerous pathways on which gluconeogenesis from fatty acids is feasible in humans. On these pathways, four moles of acetyl-CoA are converted into one mole of glucose and two moles of CO₂. Analyzing the detected pathways in detail we found that their energetic requirements potentially limit their capacity. This study has many other biochemical implications: effect of starvation, sports physiology, practically carbohydrate-free diets of inuit, as well as survival of hibernating animals and embryos of egg-laying animals. Moreover, the energetic loss associated to the usage of gluconeogenesis from fatty acids can help explain the efficiency of carbohydrate reduced and ketogenic diets such as the Atkins diet.
authors.affiliation: Department of Bioinformatics, School of Biology and Pharmaceutics, Friedrich Schiller University of Jena, Jena, Germany. christoph.kaleta@uni-jena.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaleta
authors.forename: Luís F
authors.initials: LF
authors.lastname: de Figueiredo
authors.forename: Sarah
authors.initials: S
authors.lastname: Werner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.forename: Michael
authors.initials: M
authors.lastname: Ristow
authors.forename: Stefan
authors.initials: S
authors.lastname: Schuster
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D019295:Computational Biology; D003198:Computer Simulation; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D013816:Thermodynamics
chemical_list: D005227:Fatty Acids; D002245:Carbon Dioxide; D000105:Acetyl Coenzyme A; D005947:Glucose