ENTRY       hsa04964                    Pathway
NAME        Proximal tubule bicarbonate reclamation - Homo sapiens (human)
DESCRIPTION One of the major tasks of the renal proximal tubule (PT) is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered bicarbonate (HCO3(-)), as well as generating "new HCO3(-)" for regulating blood pH. In the tubular lumen, filtered HCO3(-) combines with H(+) in a reaction catalyzed by CA IV. The CO2 thus produced rapidly diffuses into the tubular cells and is combined with water to produce intracellular H(+) and HCO3(-), catalyzed by soluble cytoplasmic CA II. HCO3(-) is then cotransported with Na(+) into blood via the NBC-1. The intracellular H(+) produced by CA II is secreted into the tubular lumen predominantly via the NHE-3. The PT creates the "new HCO3(-)" by taking glutamine and metabolizing it to two molecules each of NH4(+) and HCO3(-). The NH4(+) is excreted into the tubular lumen, and the HCO3(-) , which is "new HCO3(-) ," is returned to the blood, where it replaces the HCO3(-) lost earlier in the titration of nonvolatile acids.
CLASS       Organismal Systems; Excretory system
PATHWAY_MAP hsa04964  Proximal tubule bicarbonate reclamation
DRUG        D00218  Acetazolamide (JP18/USP/INN)
            D00518  Dichlorphenamide (USP)
            D00652  Brinzolamide (JAN/USP/INN)
            D00653  Dorzolamide hydrochloride (JP18/USP)
            D00655  Methazolamide (JAN/USP/INN)
            D01196  Acetazolamide sodium (JAN)
            D02441  Ethoxzolamide
            D03845  Sezolamide hydrochloride (USAN)
            D07871  Dorzolamide (INN)
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        6550  SLC9A3; solute carrier family 9 member A3 [KO:K12040]
            762  CA4; carbonic anhydrase 4 [KO:K18246] [EC:4.2.1.1]
            358  AQP1; aquaporin 1 (Colton blood group) [KO:K09864]
            760  CA2; carbonic anhydrase 2 [KO:K18245] [EC:4.2.1.1]
            8671  SLC4A4; solute carrier family 4 member 4 [KO:K13575]
            476  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
            477  ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:7.2.2.13]
            478  ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:7.2.2.13]
            480  ATP1A4; ATPase Na+/K+ transporting subunit alpha 4 [KO:K01539] [EC:7.2.2.13]
            23439  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
            481  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
            482  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
            483  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
            486  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
            10991  SLC38A3; solute carrier family 38 member 3 [KO:K13576]
            27165  GLS2; glutaminase 2 [KO:K01425] [EC:3.5.1.2]
            2744  GLS; glutaminase [KO:K01425] [EC:3.5.1.2]
            2747  GLUD2; glutamate dehydrogenase 2 [KO:K00261] [EC:1.4.1.3]
            2746  GLUD1; glutamate dehydrogenase 1 [KO:K00261] [EC:1.4.1.3]
            1468  SLC25A10; solute carrier family 25 member 10 [KO:K13577]
            4190  MDH1; malate dehydrogenase 1 [KO:K00025] [EC:1.1.1.37]
            5105  PCK1; phosphoenolpyruvate carboxykinase 1 [KO:K01596] [EC:4.1.1.32]
            5106  PCK2; phosphoenolpyruvate carboxykinase 2, mitochondrial [KO:K01596] [EC:4.1.1.32]
COMPOUND    C00001  H2O
            C00011  CO2
            C00014  Ammonia
            C00025  L-Glutamate
            C00026  2-Oxoglutarate
            C00036  Oxaloacetate
            C00064  L-Glutamine
            C00074  Phosphoenolpyruvate
            C00080  H+
            C00149  (S)-Malate
            C00238  Potassium cation
            C00267  alpha-D-Glucose
            C00288  HCO3-
            C00698  Cl-
            C01330  Sodium cation
            C01353  Carbonic acid
            C01358  NH4OH
REFERENCE   PMID:19948674
  AUTHORS   Koeppen BM
  TITLE     The kidney and acid-base regulation.
  JOURNAL   Adv Physiol Educ 33:275-81 (2009)
            DOI:10.1152/advan.00054.2009
REFERENCE   PMID:16914536
  AUTHORS   Boron WF
  TITLE     Acid-base transport by the renal proximal tubule.
  JOURNAL   J Am Soc Nephrol 17:2368-82 (2006)
            DOI:10.1681/ASN.2006060620
REFERENCE   PMID:9550618
  AUTHORS   Hayashi M
  TITLE     Physiology and pathophysiology of acid-base homeostasis in the kidney.
  JOURNAL   Intern Med 37:221-5 (1998)
            DOI:10.2169/internalmedicine.37.221
REFERENCE   PMID:16352913
  AUTHORS   Wagner CA, Kovacikova J, Stehberger PA, Winter C, Benabbas C, Mohebbi N
  TITLE     Renal acid-base transport: old and new players.
  JOURNAL   Nephron Physiol 103:p1-6 (2006)
            DOI:10.1159/000090217
REFERENCE   PMID:17557941
  AUTHORS   Fry AC, Karet FE
  TITLE     Inherited renal acidoses.
  JOURNAL   Physiology (Bethesda) 22:202-11 (2007)
            DOI:10.1152/physiol.00044.2006
REFERENCE   PMID:19721811
  AUTHORS   Pereira PC, Miranda DM, Oliveira EA, Silva AC
  TITLE     Molecular pathophysiology of renal tubular acidosis.
  JOURNAL   Curr Genomics 10:51-9 (2009)
            DOI:10.2174/138920209787581262
REFERENCE   PMID:12138151
  AUTHORS   Igarashi T, Sekine T, Inatomi J, Seki G
  TITLE     Unraveling the molecular pathogenesis of isolated proximal renal tubular acidosis.
  JOURNAL   J Am Soc Nephrol 13:2171-7 (2002)
            DOI:10.1097/01.ASN.0000025281.70901.30
REFERENCE   PMID:11826292
  AUTHORS   Alper SL
  TITLE     Genetic diseases of acid-base transporters.
  JOURNAL   Annu Rev Physiol 64:899-923 (2002)
            DOI:10.1146/annurev.physiol.64.092801.141759
REFERENCE   PMID:11385088
  AUTHORS   Unwin RJ, Capasso G
  TITLE     The renal tubular acidoses.
  JOURNAL   J R Soc Med 94:221-5 (2001)
            DOI:10.1177/014107680109400506
REFERENCE   PMID:11045400
  AUTHORS   Rodriguez-Soriano J
  TITLE     New insights into the pathogenesis of renal tubular acidosis--from functional to molecular studies.
  JOURNAL   Pediatr Nephrol 14:1121-36 (2000)
            DOI:10.1007/s004670000407
REFERENCE   PMID:18056784
  AUTHORS   Nowik M, Lecca MR, Velic A, Rehrauer H, Brandli AW, Wagner CA
  TITLE     Genome-wide gene expression profiling reveals renal genes regulated during metabolic acidosis.
  JOURNAL   Physiol Genomics 32:322-34 (2008)
            DOI:10.1152/physiolgenomics.00160.2007
REFERENCE   PMID:11533299
  AUTHORS   Curthoys NP
  TITLE     Role of mitochondrial glutaminase in rat renal glutamine metabolism.
  JOURNAL   J Nutr 131:2491S-5S; discussion 2496S-7S (2001)
            DOI:10.1093/jn/131.9.2491S
REL_PATHWAY hsa00010  Glycolysis / Gluconeogenesis
            hsa00020  Citrate cycle (TCA cycle)
            hsa04530  Tight junction
KO_PATHWAY  ko04964
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