Fructose metabolism in proximal tubules (WP3894)

Rattus norvegicus

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Most of the fructose absorbed in the gut is cleared in its first hepatic passage; however, under certain conditions, such as ingestion of large amounts of free fructose, the sugar can reach high levels in plasma and filtrate through the glomeruli. Filtered fructose is reabsorbed by proximal tubule cells. Ingestion of large quantities of free fructose, usually from high fructose corn syrup, has been associated with obesity, metabolic syndrome and elevated blood pressure. Salt-sensitivity of blood pressure in rodents receiving 10 or 20% fructose solutions is well documented. Sensitivity to salt, should include a renal defect, otherwise pressure natriuretis would restore Na balance. Since the bulk of fructose and other sugars are absorbed in proximal tubules, it is believed that fructose affect this nephron segment first. This pathway features the metabolism of fructose in proximal tubule cells. It was created using biochemical data showing metabolites accumulation and enzymatic activities in proximal tubules challenged with fructose. Also deep sequencing data from microdissected renal proximal tubules was used to confirm the presence of the transcript of the enzymes. Gene transcripts are annotated using ENTREZ Gene ID.

Authors

Agustin Gonzalez-Vicente , Egon Willighagen , Kristina Hanspers , Denise Slenter , and Eric Weitz

Activity

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Organisms

Rattus norvegicus

Communities

Renal Genomics Pathways

Annotations

Disease Ontology

renal hypertension hereditary fructose intolerance syndrome fructose-1,6-bisphosphatase deficiency hypertension

Cell Type Ontology

epithelial cell of proximal tubule

Pathway Ontology

carbohydrate metabolic pathway

Participants

Label Type Compact URI Comment
Fructose Metabolite hmdb:HMDB0000660
Glucose Metabolite hmdb:HMDB0000122
Glucose-6-P Metabolite hmdb:HMDB0001401
Fructose-6-P Metabolite hmdb:HMDB0000124
Sorbitol Metabolite hmdb:HMDB0000247
Fructose-1-P Metabolite hmdb:HMDB0001076
Fructose-1,6-biP Metabolite hmdb:HMDB0001058
Glyderaldehyde-3-P Metabolite hmdb:HMDB0001112
Dihydroacetone-P Metabolite hmdb:HMDB0001473
Glyderaldehyde Metabolite hmdb:HMDB0001051
Aldoa GeneProduct ncbigene:24189
Gpi GeneProduct ncbigene:292804
Tkfc GeneProduct ncbigene:361730
Sord GeneProduct ncbigene:24788
Fbp1 GeneProduct ncbigene:24362
G6pc GeneProduct ncbigene:25634
Pfkl GeneProduct ncbigene:25741
Akr1b1 GeneProduct ncbigene:24192
Khk GeneProduct ncbigene:25659
Aldob GeneProduct ncbigene:24190
Tpi1 GeneProduct ncbigene:24849
Aldob GeneProduct ncbigene:24190
Hk1 GeneProduct ncbigene:25058
Pfkp GeneProduct ncbigene:60416
Pfkm GeneProduct ncbigene:65152
Hk1 GeneProduct ncbigene:25058 Low affinity for fructose
Slc5a10 GeneProduct ncbigene:303205
Slc2a5 GeneProduct ncbigene:65197
Slc5a9 GeneProduct ncbigene:366441
Naglt1 GeneProduct ncbigene:337920

References

  1. Effect of fructose, dihydroxyacetone, glycerol, and glucose on metabolites and related compounds in liver and kidney. Burch HB, Lowry OH, Meinhardt L, Max P Jr, Chyu K. J Biol Chem. 1970 Apr 25;245(8):2092–102. PubMed Europe PMC Scholia
  2. Metabolic effects of large fructose loads in different parts of the rat nephron. Burch HB, Choi S, Dence CN, Alvey TR, Cole BR, Lowry OH. J Biol Chem. 1980 Sep 10;255(17):8239–44. PubMed Europe PMC Scholia
  3. Na(+)-dependent fructose transport via rNaGLT1 in rat kidney. Horiba N, Masuda S, Ohnishi C, Takeuchi D, Okuda M, Inui K ichi. FEBS Lett. 2003 Jul 10;546(2–3):276–80. PubMed Europe PMC Scholia
  4. SLC5A9/SGLT4, a new Na+-dependent glucose transporter, is an essential transporter for mannose, 1,5-anhydro-D-glucitol, and fructose. Tazawa S, Yamato T, Fujikura H, Hiratochi M, Itoh F, Tomae M, et al. Life Sci. 2005 Jan 14;76(9):1039–50. PubMed Europe PMC Scholia
  5. Functional characterisation of human SGLT-5 as a novel kidney-specific sodium-dependent sugar transporter. Grempler R, Augustin R, Froehner S, Hildebrandt T, Simon E, Mark M, et al. FEBS Lett. 2012 Feb 3;586(3):248–53. PubMed Europe PMC Scholia
  6. SGLT5 reabsorbs fructose in the kidney but its deficiency paradoxically exacerbates hepatic steatosis induced by fructose. Fukuzawa T, Fukazawa M, Ueda O, Shimada H, Kito A, Kakefuda M, et al. PLoS One. 2013;8(2):e56681. PubMed Europe PMC Scholia
  7. Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment-Specific Transcriptomes. Lee JW, Chou CL, Knepper MA. J Am Soc Nephrol. 2015 Nov;26(11):2669–77. PubMed Europe PMC Scholia
  8. Transcriptome signature for dietary fructose-specific changes in rat renal cortex: A quantitative approach to physiological relevance. Gonzalez-Vicente A, Garvin JL, Hopfer U. PLoS One. 2018 Aug 1;13(8):e0201293. PubMed Europe PMC Scholia
  9. Fructose reabsorption by rat proximal tubules: role of Na+-linked cotransporters and the effect of dietary fructose. Gonzalez-Vicente A, Cabral PD, Hong NJ, Asirwatham J, Saez F, Garvin JL. Am J Physiol Renal Physiol. 2019 Mar 1;316(3):F473–80. PubMed Europe PMC Scholia