Fructose metabolism in proximal tubules (Rattus norvegicus)

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1, 5, 7-92, 3, 6, 8Payoff phase of glycolysis Polyol Pathwayspecific stepsLow affinityfor fructoseGpiAkr1b1GlucoseTkfcG6pcPfklFructoseFbp1SordNeutral lipidSynthesisKhkAldoaGlucose-6-PFructose-6-PSorbitolFructose-1-PFructose-1,6-biPGlyderaldehyde-3-PDihydroacetone-PGlyderaldehydeAldobTpi1AldobHk1PfkpPfkmHk1Rate limitingstepSlc5a10Slc2a5Slc5a9Naglt1Fructosetransporters42


Description

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.

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Bibliography

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  1. Lee JW, Chou CL, Knepper MA; ''Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment-Specific Transcriptomes.''; J Am Soc Nephrol, 2015 PubMed Europe PMC Scholia
  2. Gonzalez-Vicente A, Cabral PD, Hong NJ, Asirwatham J, Saez F, Garvin JL; ''Fructose reabsorption by rat proximal tubules: role of Na+-linked cotransporters and the effect of dietary fructose.''; Am J Physiol Renal Physiol, 2019 PubMed Europe PMC Scholia
  3. Fukuzawa T, Fukazawa M, Ueda O, Shimada H, Kito A, Kakefuda M, Kawase Y, Wada NA, Goto C, Fukushima N, Jishage K, Honda K, King GL, Kawabe Y; ''''; , PubMed Europe PMC Scholia
  4. Horiba N, Masuda S, Ohnishi C, Takeuchi D, Okuda M, Inui K; ''Na(+)-dependent fructose transport via rNaGLT1 in rat kidney.''; FEBS Lett, 2003 PubMed Europe PMC Scholia
  5. Burch HB, Lowry OH, Meinhardt L, Max P Jr, Chyu K; ''''; , PubMed Europe PMC Scholia
  6. Tazawa S, Yamato T, Fujikura H, Hiratochi M, Itoh F, Tomae M, Takemura Y, Maruyama H, Sugiyama T, Wakamatsu A, Isogai T, Isaji M; ''''; , PubMed Europe PMC Scholia
  7. Gonzalez-Vicente A, Garvin JL, Hopfer U; ''Transcriptome signature for dietary fructose-specific changes in rat renal cortex: A quantitative approach to physiological relevance.''; PLoS One, 2018 PubMed Europe PMC Scholia
  8. Grempler R, Augustin R, Froehner S, Hildebrandt T, Simon E, Mark M, Eickelmann P; ''''; , PubMed Europe PMC Scholia
  9. Burch HB, Choi S, Dence CN, Alvey TR, Cole BR, Lowry OH.; ''''; , PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
126100view14:44, 5 April 2023AgustinGVUpdate bibliography
126099view14:40, 5 April 2023AgustinGVUpdate Transporters
123401view06:27, 23 July 2022EgonwMade a pathway clickable
116966view10:25, 16 May 2021EweitzModified title
108294view17:34, 4 December 2019AgustinGVAdd new reference
106987view13:44, 17 September 2019MaintBotHMDB identifier normalization
98285view13:17, 16 August 2018DeSlConnected all enzymes properly (with MIM-catalysis symbol); changed layout for readability.
98212view12:35, 9 August 2018AgustinGVnew ref
91517view18:54, 8 March 2017Khanspersfixed xref for pathway node
90399view14:55, 11 November 2016AgustinGVModified description
90398view14:41, 11 November 2016AgustinGVReferences added
90397view14:38, 11 November 2016AgustinGVSpecify description
90396view14:37, 11 November 2016AgustinGVModified title
90395view14:35, 11 November 2016AgustinGVAdd Fructose Transporters
90394view14:05, 11 November 2016AgustinGVMore info on text
90393view14:02, 11 November 2016AgustinGVAdd descriptions and info on text
90392view13:56, 11 November 2016AgustinGVSpecify description
90391view13:56, 11 November 2016AgustinGVSpecify description
90386view21:57, 10 November 2016AgustinGVSpecify description
90385view21:14, 10 November 2016AgustinGV
90383view18:30, 10 November 2016AgustinGV
90382view18:26, 10 November 2016AgustinGV
90381view18:23, 10 November 2016AgustinGV
89604view18:08, 19 September 2016AgustinGVModified description
89603view18:05, 19 September 2016AgustinGVModified description
89598view16:00, 19 September 2016AgustinGVOntology Term : 'hypertension' added !
89597view15:59, 19 September 2016AgustinGVOntology Term : 'renal hypertension' added !
89596view15:59, 19 September 2016AgustinGVOntology Term : 'epithelial cell of proximal tubule' added !
89595view15:59, 19 September 2016AgustinGVModified description
89569view07:53, 17 September 2016EgonwFixed casing in two HDMB identifiers.
89566view13:53, 16 September 2016AgustinGVCorrect misalignment
89565view13:46, 16 September 2016AgustinGVCorrect misalignment
89559view13:35, 16 September 2016AgustinGVAdd ID
89558view13:33, 16 September 2016AgustinGVModified description
89557view13:32, 16 September 2016AgustinGVAdd ID
89556view13:31, 16 September 2016AgustinGVAdd ID
89555view13:30, 16 September 2016AgustinGVAdd Identifier
89554view13:28, 16 September 2016AgustinGVSpecify description
89550view13:23, 16 September 2016AgustinGVModified description
89549view13:23, 16 September 2016AgustinGVModified description
89499view16:24, 15 September 2016AgustinGVOntology Term : 'hereditary fructose intolerance syndrome' added !
89498view16:23, 15 September 2016AgustinGVOntology Term : 'fructose-1,6-bisphosphatase deficiency' added !
89497view16:22, 15 September 2016AgustinGVOntology Term : 'carbohydrate metabolic pathway' added !
89495view16:11, 15 September 2016AgustinGVSpecify description
89494view15:59, 15 September 2016AgustinGVNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
Akr1b1GeneProduct24192 (Entrez Gene)
AldoaGeneProduct24189 (Entrez Gene)
AldobGeneProduct24190 (Entrez Gene)
Dihydroacetone-PMetaboliteHMDB0001473 (HMDB)
Fbp1GeneProduct24362 (Entrez Gene)
Fructose-1,6-biPMetaboliteHMDB0001058 (HMDB)
Fructose-1-PMetaboliteHMDB0001076 (HMDB)
Fructose-6-PMetaboliteHMDB0000124 (HMDB)
FructoseMetaboliteHMDB0000660 (HMDB)
G6pcGeneProduct25634 (Entrez Gene)
Glucose-6-PMetaboliteHMDB0001401 (HMDB)
GlucoseMetaboliteHMDB0000122 (HMDB)
Glyderaldehyde-3-PMetaboliteHMDB0001112 (HMDB)
GlyderaldehydeMetaboliteHMDB0001051 (HMDB)
GpiGeneProduct292804 (Entrez Gene)
Hk1GeneProduct25058 (Entrez Gene) Low affinity for fructose
KhkGeneProduct25659 (Entrez Gene)
Naglt1GeneProduct337920 (Entrez Gene)
Neutral lipid SynthesisPathwayWP3901 (WikiPathways)
PfklGeneProduct25741 (Entrez Gene)
PfkmGeneProduct65152 (Entrez Gene)
PfkpGeneProduct60416 (Entrez Gene)
Slc2a5GeneProduct65197 (Entrez Gene)
Slc5a10GeneProduct303205 (Entrez Gene)
Slc5a9GeneProduct366441 (Entrez Gene)
SorbitolMetaboliteHMDB0000247 (HMDB)
SordGeneProduct24788 (Entrez Gene)
TkfcGeneProduct361730 (Entrez Gene)
Tpi1GeneProduct24849 (Entrez Gene)

Annotated Interactions

No annotated interactions

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