KEGG   PATHWAY: hsa04964
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
hsa04964

Drug
D00218  Acetazolamide (JP17/USP/INN)
D00518  Dichlorphenamide (USP)
D00652  Brinzolamide (JAN/USP/INN)
D00653  Dorzolamide hydrochloride (JP17/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
  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
  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
  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
  Authors
Fry AC, Karet FE
  Title
Inherited renal acidoses.
  Journal
Physiology (Bethesda) 22:202-11 (2007)
DOI:10.1152/physiol.00044.2006
Reference
  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
  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
  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
  Authors
Unwin RJ, Capasso G
  Title
The renal tubular acidoses.
  Journal
J R Soc Med 94:221-5 (2001)
DOI:10.1177/014107680109400506
Reference
  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
  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
  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
Related
pathway
hsa00010  Glycolysis / Gluconeogenesis
hsa00020  Citrate cycle (TCA cycle)
hsa04530  Tight junction
KO pathway
ko04964   

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