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In silico evidence for gluconeogenesis from fatty acids in humans.

Kaleta C, de Figueiredo LF, Werner S, Guthke R, Ristow M, Schuster S - PLoS Comput. Biol. (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics, School of Biology and Pharmaceutics, Friedrich Schiller University of Jena, Jena, Germany. christoph.kaleta@uni-jena.de

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.

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Schematic representation of the iteration process for searching pathways.Black arrows correspond to reactions belonging to the subsystems. A, D and F Subsystems used in the different iteration steps. B, C and E Selected elementary flux patterns (thick black arrows) and the reactions used by an associated elementary mode in the remaining system (thick gray arrows). If only one direction of a reversible reaction belongs to a subsystem, the reverse direction is omitted for clarity. G and H Elementary flux patterns of the final system producing R5P with the associated pathways through the entire system. A list of abbreviations can be found in Table S1.
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pcbi-1002116-g008: Schematic representation of the iteration process for searching pathways.Black arrows correspond to reactions belonging to the subsystems. A, D and F Subsystems used in the different iteration steps. B, C and E Selected elementary flux patterns (thick black arrows) and the reactions used by an associated elementary mode in the remaining system (thick gray arrows). If only one direction of a reversible reaction belongs to a subsystem, the reverse direction is omitted for clarity. G and H Elementary flux patterns of the final system producing R5P with the associated pathways through the entire system. A list of abbreviations can be found in Table S1.

Mentions: Elementary flux patterns can be used to elucidate all possible pathways consuming a certain compound and producing another. This process builds upon a successive expansion of the subsystem under study to reactions that belong to alternative pathways. It will be outlined by way of a small example network comprising glycolysis and the pentose phosphate pathway (Fig. 8). Within this system we want to find all pathways producing ribose-5-phosphate (R5P), a precursor of histidine and nucleotide syntheses from glucose (Glc).


In silico evidence for gluconeogenesis from fatty acids in humans.

Kaleta C, de Figueiredo LF, Werner S, Guthke R, Ristow M, Schuster S - PLoS Comput. Biol. (2011)

Schematic representation of the iteration process for searching pathways.Black arrows correspond to reactions belonging to the subsystems. A, D and F Subsystems used in the different iteration steps. B, C and E Selected elementary flux patterns (thick black arrows) and the reactions used by an associated elementary mode in the remaining system (thick gray arrows). If only one direction of a reversible reaction belongs to a subsystem, the reverse direction is omitted for clarity. G and H Elementary flux patterns of the final system producing R5P with the associated pathways through the entire system. A list of abbreviations can be found in Table S1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140964&req=5

pcbi-1002116-g008: Schematic representation of the iteration process for searching pathways.Black arrows correspond to reactions belonging to the subsystems. A, D and F Subsystems used in the different iteration steps. B, C and E Selected elementary flux patterns (thick black arrows) and the reactions used by an associated elementary mode in the remaining system (thick gray arrows). If only one direction of a reversible reaction belongs to a subsystem, the reverse direction is omitted for clarity. G and H Elementary flux patterns of the final system producing R5P with the associated pathways through the entire system. A list of abbreviations can be found in Table S1.
Mentions: Elementary flux patterns can be used to elucidate all possible pathways consuming a certain compound and producing another. This process builds upon a successive expansion of the subsystem under study to reactions that belong to alternative pathways. It will be outlined by way of a small example network comprising glycolysis and the pentose phosphate pathway (Fig. 8). Within this system we want to find all pathways producing ribose-5-phosphate (R5P), a precursor of histidine and nucleotide syntheses from glucose (Glc).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics, School of Biology and Pharmaceutics, Friedrich Schiller University of Jena, Jena, Germany. christoph.kaleta@uni-jena.de

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.

Show MeSH
Related in: MedlinePlus