KEGG   PATHWAY: hsa04964Help
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
BRITE hierarchy
Pathway map
hsa04964  Proximal tubule bicarbonate reclamation
hsa04964

Ortholog table
Disease
H00241  Combined proximal and distal renal tubular acidosis
H00429  Proximal renal tubular acidosis (RTA type 2)
H00998  Alternating hemiplegia of childhood
H02310  Renal tubular acidosis
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)
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)
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
KO pathway
ko04964   

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