KEGG   PATHWAY: mmu04964Help
Entry
mmu04964                    Pathway                                
Name
Proximal tubule bicarbonate reclamation - Mus musculus (mouse)
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
Proximal tubule bicarbonate reclamation
mmu04964

All organismsOrtholog table
Organism
Mus musculus (mouse) [GN:mmu]
Gene
105243  
Slc9a3; solute carrier family 9 (sodium/hydrogen exchanger), member 3 [KO:K12040]
11826  
Aqp1; aquaporin 1 [KO:K09864]
54403  
Slc4a4; solute carrier family 4 (anion exchanger), member 4 [KO:K13575]
11928  
Atp1a1; ATPase, Na+/K+ transporting, alpha 1 polypeptide [KO:K01539] [EC:3.6.3.9]
98660  
Atp1a2; ATPase, Na+/K+ transporting, alpha 2 polypeptide [KO:K01539] [EC:3.6.3.9]
232975  
Atp1a3; ATPase, Na+/K+ transporting, alpha 3 polypeptide [KO:K01539] [EC:3.6.3.9]
27222  
Atp1a4; ATPase, Na+/K+ transporting, alpha 4 polypeptide [KO:K01539] [EC:3.6.3.9]
67821  
Atp1b4; ATPase, (Na+)/K+ transporting, beta 4 polypeptide [KO:K01540]
11931  
Atp1b1; ATPase, Na+/K+ transporting, beta 1 polypeptide [KO:K01540]
11932  
Atp1b2; ATPase, Na+/K+ transporting, beta 2 polypeptide [KO:K01540]
11933  
Atp1b3; ATPase, Na+/K+ transporting, beta 3 polypeptide [KO:K01540]
11936  
Fxyd2; FXYD domain-containing ion transport regulator 2 [KO:K01538]
76257  
Slc38a3; solute carrier family 38, member 3 [KO:K13576]
216456  
Gls2; glutaminase 2 (liver, mitochondrial) [KO:K01425] [EC:3.5.1.2]
14660  
Gls; glutaminase [KO:K01425] [EC:3.5.1.2]
14661  
Glud1; glutamate dehydrogenase 1 [KO:K00261] [EC:1.4.1.3]
27376  
Slc25a10; solute carrier family 25 (mitochondrial carrier, dicarboxylate transporter), member 10 [KO:K13577]
17449  
Mdh1; malate dehydrogenase 1, NAD (soluble) [KO:K00025] [EC:1.1.1.37]
18534  
Pck1; phosphoenolpyruvate carboxykinase 1, cytosolic [KO:K01596] [EC:4.1.1.32]
74551  
Pck2; phosphoenolpyruvate carboxykinase 2 (mitochondrial) [KO:K01596] [EC:4.1.1.32]
Compound
C00001  
H2O
C00011  
CO2
C00014  
NH3
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)
Reference
  Authors
Boron WF
  Title
Acid-base transport by the renal proximal tubule.
  Journal
J Am Soc Nephrol 17:2368-82 (2006)
Reference
PMID:9550618
  Authors
Hayashi M
  Title
Physiology and pathophysiology of acid-base homeostasis in the kidney.
  Journal
Intern Med 37:221-5 (1998)
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)
Reference
  Authors
Fry AC, Karet FE
  Title
Inherited renal acidoses.
  Journal
Physiology (Bethesda) 22:202-11 (2007)
Reference
  Authors
Pereira PC, Miranda DM, Oliveira EA, Silva AC
  Title
Molecular pathophysiology of renal tubular acidosis.
  Journal
Curr Genomics 10:51-9 (2009)
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)
Reference
  Authors
Alper SL
  Title
Genetic diseases of acid-base transporters.
  Journal
Annu Rev Physiol 64:899-923 (2002)
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)
Reference
  Authors
Curthoys NP
  Title
Role of mitochondrial glutaminase in rat renal glutamine metabolism.
  Journal
J Nutr 131:2491S-5S; discussion 2496S-7S (2001)
KO pathway
 
DBGET integrated database retrieval system