Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Kidney Function- Proximal Convoluted Tubule
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Physiological
Created: 2018-10-25
Last Updated: 2023-10-28
The proximal convoluted tubule is part of the nephron between the Bowman's capsule and the loop of Henle. The proximal convoluted tubule functions to reabsorb sodium, water, and other ions. Sodium and bicarbonate (hydrogen carbonate) are transported by a co-transporter that is responsible for the majority of sodium reabsorption. The bicarbonate, along with hydrogen, are exchanged across the basal and apical membranes, respectively, to effectively regulate the pH of the filtrate. In addition, chloride ions are not normally reabsorbed in large amounts at the proximal tubule compared to other parts of the nephron. However, the reabsorption of chloride, as well as potassium, increases as the amount of water reabsorption increases due to solvent drag (also known as bulk transport). This occurrence explains solute movement secondary to water flow. All the cation and anion transport creates a gradient favourable for ion and water reabsorption, leading to an increase in blood pressure.
References
Kidney Function- Proximal Convoluted Tubule References
Wang T: Flow-activated transport events along the nephron. Curr Opin Nephrol Hypertens. 2006 Sep;15(5):530-6. doi: 10.1097/01.mnh.0000242180.46362.c4.
Pubmed: 16914967
Lucci MS, Warnock DG: Effects of anion-transport inhibitors on NaCl reabsorption in the rat superficial proximal convoluted tubule. J Clin Invest. 1979 Aug;64(2):570-9. doi: 10.1172/JCI109495.
Pubmed: 457869
Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook EH Jr: Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder. Mol Psychiatry. 2001 Mar;6(2):160-7. doi: 10.1038/sj.mp.4000806.
Pubmed: 11317217
Myles-Worsley M, Tiobech J, Browning SR, Korn J, Goodman S, Gentile K, Melhem N, Byerley W, Faraone SV, Middleton FA: Deletion at the SLC1A1 glutamate transporter gene co-segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family. Am J Med Genet B Neuropsychiatr Genet. 2013 Mar;162B(2):87-95. doi: 10.1002/ajmg.b.32125. Epub 2013 Jan 22.
Pubmed: 23341099
Bailey CG, Ryan RM, Thoeng AD, Ng C, King K, Vanslambrouck JM, Auray-Blais C, Vandenberg RJ, Broer S, Rasko JE: Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. J Clin Invest. 2011 Jan;121(1):446-53. doi: 10.1172/JCI44474. Epub 2010 Dec 1.
Pubmed: 21123949
Mastroberardino L, Spindler B, Pfeiffer R, Skelly PJ, Loffing J, Shoemaker CB, Verrey F: Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family. Nature. 1998 Sep 17;395(6699):288-91. doi: 10.1038/26246.
Pubmed: 9751058
Prasad PD, Wang H, Huang W, Kekuda R, Rajan DP, Leibach FH, Ganapathy V: Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function. Biochem Biophys Res Commun. 1999 Feb 16;255(2):283-8. doi: 10.1006/bbrc.1999.0206.
Pubmed: 10049700
Tsurudome M, Ito M, Takebayashi S, Okumura K, Nishio M, Kawano M, Kusagawa S, Komada H, Ito Y: Cutting edge: primary structure of the light chain of fusion regulatory protein-1/CD98/4F2 predicts a protein with multiple transmembrane domains that is almost identical to the amino acid transporter E16. J Immunol. 1999 Mar 1;162(5):2462-6.
Pubmed: 10072483
Quackenbush E, Clabby M, Gottesdiener KM, Barbosa J, Jones NH, Strominger JL, Speck S, Leiden JM: Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6526-30. doi: 10.1073/pnas.84.18.6526.
Pubmed: 3476959
Teixeira S, Di Grandi S, Kuhn LC: Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus. J Biol Chem. 1987 Jul 15;262(20):9574-80.
Pubmed: 3036867
Lumadue JA, Glick AB, Ruddle FH: Cloning, sequence analysis, and expression of the large subunit of the human lymphocyte activation antigen 4F2. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9204-8. doi: 10.1073/pnas.84.24.9204.
Pubmed: 3480538
Kiss H, Kedra D, Kiss C, Kost-Alimova M, Yang Y, Klein G, Imreh S, Dumanski JP: The LZTFL1 gene is a part of a transcriptional map covering 250 kb within the common eliminated region 1 (C3CER1) in 3p21.3. Genomics. 2001 Apr 1;73(1):10-9. doi: 10.1006/geno.2000.6498.
Pubmed: 11352561
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Nash SR, Giros B, Kingsmore SF, Kim KM, el-Mestikawy S, Dong Q, Fumagalli F, Seldin MF, Caron MG: Cloning, gene structure and genomic localization of an orphan transporter from mouse kidney with six alternatively-spliced isoforms. Receptors Channels. 1998;6(2):113-28.
Pubmed: 9932288
Torrents D, Estevez R, Pineda M, Fernandez E, Lloberas J, Shi YB, Zorzano A, Palacin M: Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance. J Biol Chem. 1998 Dec 4;273(49):32437-45. doi: 10.1074/jbc.273.49.32437.
Pubmed: 9829974
Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N: Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res. 1996 Oct 31;3(5):321-9, 341-54. doi: 10.1093/dnares/3.5.321.
Pubmed: 9039502
Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. doi: 10.1186/1471-2164-8-399.
Pubmed: 17974005
Endsley JK, Phillips JA 3rd, Hruska KA, Denneberg T, Carlson J, George AL Jr: Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria. Kidney Int. 1997 Jun;51(6):1893-9. doi: 10.1038/ki.1997.258.
Pubmed: 9186880
Calonge MJ, Volpini V, Bisceglia L, Rousaud F, de Sanctis L, Beccia E, Zelante L, Testar X, Zorzano A, Estivill X, et al.: Genetic heterogeneity in cystinuria: the SLC3A1 gene is linked to type I but not to type III cystinuria. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9667-71. doi: 10.1073/pnas.92.21.9667.
Pubmed: 7568194
Pras E, Raben N, Golomb E, Arber N, Aksentijevich I, Schapiro JM, Harel D, Katz G, Liberman U, Pras M, et al.: Mutations in the SLC3A1 transporter gene in cystinuria. Am J Hum Genet. 1995 Jun;56(6):1297-303.
Pubmed: 7539209
Feliubadalo L, Font M, Purroy J, Rousaud F, Estivill X, Nunes V, Golomb E, Centola M, Aksentijevich I, Kreiss Y, Goldman B, Pras M, Kastner DL, Pras E, Gasparini P, Bisceglia L, Beccia E, Gallucci M, de Sanctis L, Ponzone A, Rizzoni GF, Zelante L, Bassi MT, George AL Jr, Manzoni M, De Grandi A, Riboni M, Endsley JK, Ballabio A, Borsani G, Reig N, Fernandez E, Estevez R, Pineda M, Torrents D, Camps M, Lloberas J, Zorzano A, Palacin M: Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT. Nat Genet. 1999 Sep;23(1):52-7. doi: 10.1038/12652.
Pubmed: 10471498
Leclerc D, Boutros M, Suh D, Wu Q, Palacin M, Ellis JR, Goodyer P, Rozen R: SLC7A9 mutations in all three cystinuria subtypes. Kidney Int. 2002 Nov;62(5):1550-9. doi: 10.1046/j.1523-1755.2002.00602.x.
Pubmed: 12371955
Botzenhart E, Vester U, Schmidt C, Hesse A, Halber M, Wagner C, Lang F, Hoyer P, Zerres K, Eggermann T: Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 genes. Kidney Int. 2002 Oct;62(4):1136-42. doi: 10.1111/j.1523-1755.2002.kid552.x.
Pubmed: 12234283
Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H: Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81. doi: 10.1089/dna.1997.16.871.
Pubmed: 9260930
Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. doi: 10.1097/01.asn.0000019413.78751.46.
Pubmed: 12089365
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings