Disorders of fructose metabolism (WP5178)

Homo sapiens

Fructose is converted into fructose-1-phosphate, this reaction is facilitated by fructokinase (also called ketohexokinase)(encoded by KHK). Connected to this reaction is the metabolic disease "essential fructosuria" which causes a deficiency in fructokinase. After this fructose-1-phosphate is converted into glyceraldehyde and dihydroxyacetone-phosphate, this is facilitated by aldolase B (encoded by ALDOB). connected to this reaction is the metabolic disease "hereditary fructose intolerance", which is the result of the absence of aldolase B. The glyceraldehyde produced from this reaction will be converted into D-glycerate through the activity of Aldehyde dehydrogenase 1 family, member A1 or ALDH1A1 (encoded by the ALDH1A1 gene). The D-glycerate will be converted (according to the book) into 2-Phosphoglyceric acid through the activity of Glycerate kinase (encoded by GLYCTK), connected to this reaction is the metabolic disease "glycerate kinase deficiency" which results in the accumulation of D-glycerate. The resulting 2-phosphoglyceric acid then goes through a series of reactions resulting in pyruvate. Another entry into this pathway is through the conversion of glucose-6-phosphate into fructose-6-phosphate through glucose-6-phosphate isomerase (encoded by GPI). The fructose-6-phosphate can be converted into fructose-1,6-biphosphate through phosphofructokinase (encoded by PFKL). Fructose-1,6-biphosphate can be converted into fructose-6-phosphate by fructose-1,6-biphosphatase, connected to this reaction is the metabolic disease "Fructose-1,6-biphosphatase deficiency". When going further, the fructose-1,6-biphosphate is converted into dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate through the activity of aldolase B, this reaction is also affected by hereditary fructose intolerance. The glyceraldehyde-3-phosphate is then eventually turned into pyruvate through a series of reactions. The dihydroxyacetone-phosphate resulting from the aldolase B involved reactions can be converted into glyceraldehyde-3-phosphate through the activity of triose-phosphate isomerase (encoded by TPI1). This pathway is based on the fructose metabolism pathway (Chapter 18, Figure 18.5) in the book Physicians Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases (ed. 4) by Nenad Blau, Marinus Duran, K Michael Gibson, Carlo Dionisi.(ISBN 3642403360 (978-3642403361))


Enzo Chiaradia , Sam Drabbe , Egon Willighagen , Lars Willighagen , and Eric Weitz


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Homo sapiens


Inherited Metabolic Disorders (IMD) Pathways Rare Diseases


Pathway Ontology

carbohydrate metabolic pathway inborn error of fructose metabolism pathway

Disease Ontology

essential fructosuria retinitis pigmentosa hereditary fructose intolerance syndrome D-glyceric aciduria congenital disorder of glycosylation fructose-1,6-bisphosphatase deficiency


Label Type Compact URI Comment
Sorbitol Metabolite chebi:30911
Glc-1-P Metabolite chebi:16077
Glyceraldehyde-3-P Metabolite chebi:29052
Glyceraldehyde Metabolite chebi:17378
Sucrose Metabolite chebi:17992
Glucose Metabolite chebi:17234
Frc-1,6-P2 Metabolite chebi:32966
Frc-6-P Metabolite chebi:57634
Glycogen Metabolite chebi:28087
Fructose Metabolite chebi:28645
2-P-Glycerate Metabolite chebi:17835
pyruvate Metabolite chebi:15361
D-glycerate Metabolite chebi:16659
Frc-1-P Metabolite chebi:138881
Dihydroxyacetone-P Metabolite chebi:16108
Fructose Metabolite chebi:28645
Sorbitol Metabolite chebi:30911
Glucose Metabolite chebi:17234
Glc-6-P Metabolite chebi:58225
Glc Metabolite chebi:17234
Glc Metabolite chebi:17234
Glc 6-P Metabolite chebi:4170
SLC2A2 GeneProduct ensembl:ENSG00000163581
ALDH1A1 GeneProduct ensembl:ENSG00000165092
PGM1 GeneProduct ensembl:ENSG00000079739
GLYCTK GeneProduct ensembl:ENSG00000168237
PFKL GeneProduct ensembl:ENSG00000141959
GPI GeneProduct ensembl:ENSG00000105220
G6PC GeneProduct ensembl:ENSG00000131482
SORD GeneProduct ensembl:ENSG00000140263
FBP1 GeneProduct ensembl:ENSG00000165140
SLC5A1 GeneProduct ensembl:ENSG00000100170
TPI1 GeneProduct ensembl:ENSG00000111669
KHK GeneProduct ensembl:ENSG00000138030
ALDOB GeneProduct ensembl:ENSG00000136872
HK1 GeneProduct ensembl:ENSG00000156515


  1. Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Blau N, Duran M, Gibson KM, Dionisi Vici C, editors. Springer Berlin Heidelberg; 2014. Available from: http://dx.doi.org/10.1007/978-3-642-40337-8 DOI Scholia
  2. Escherichia coli ☆. Neidhardt FC, Kushner SR. In: Reference Module in Life Sciences [Internet]. Elsevier; 2017. Available from: http://dx.doi.org/10.1016/B978-0-12-809633-8.06393-7 DOI Scholia
  3. Activity and specificity of human aldolases. Gamblin SJ, Davies GJ, Grimes JM, Jackson RM, Littlechild JA, Watson HC. J Mol Biol. 1991 Jun 20;219(4):573–6. PubMed Europe PMC Scholia
  4. Properties of normal and mutant recombinant human ketohexokinases and implications for the pathogenesis of essential fructosuria. Asipu A, Hayward BE, O’Reilly J, Bonthron DT. Diabetes. 2003 Sep;52(9):2426–32. PubMed Europe PMC Scholia
  5. D-glyceric aciduria is caused by genetic deficiency of D-glycerate kinase (GLYCTK). Sass JO, Fischer K, Wang R, Christensen E, Scholl-Bürgi S, Chang R, et al. Hum Mutat. 2010 Dec;31(12):1280–5. PubMed Europe PMC Scholia
  6. New insights into the half-of-the-sites reactivity of human aldehyde dehydrogenase 1A1. Yoval-Sánchez B, Pardo JP, Rodríguez-Zavala JS. Proteins. 2013 Aug;81(8):1330–9. PubMed Europe PMC Scholia
  7. The metabolic alterations of cancer cells. Sciacovelli M, Gaude E, Hilvo M, Frezza C. Methods Enzymol. 2014;542:1–23. PubMed Europe PMC Scholia
  8. Two novel mutations (p.(Ser160Pro) and p.(Arg472Cys)) causing glucose-6-phosphate isomerase deficiency are associated with erythroid dysplasia and inappropriately suppressed hepcidin. Mojzikova R, Koralkova P, Holub D, Saxova Z, Pospisilova D, Prochazkova D, et al. Blood Cells Mol Dis. 2018 Mar;69:23–9. PubMed Europe PMC Scholia