KEGG   PATHWAY: ko04964Help
Entry
ko04964                     Pathway                                

Name
Proximal tubule bicarbonate reclamation
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
ko04964

All organismsOrtholog table
Disease
H00241  
Combined proximal and distal renal tubular acidosis (RTA type 3)
H00429  
Proximal renal tubular acidosis (RTA type 2)
H00998  
Alternating hemiplegia of childhood
Orthology
K12040  
solute carrier family 9 (sodium/hydrogen exchanger), member 3
K09864  
aquaporin-1
K13575  
solute carrier family 4 (sodium bicarbonate cotransporter), member 4
K01539  
sodium/potassium-transporting ATPase subunit alpha [EC:3.6.3.9]
K01540  
sodium/potassium-transporting ATPase subunit beta
K01538  
sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K13576  
solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 3
K01425  
glutaminase [EC:3.5.1.2]
K00261  
glutamate dehydrogenase (NAD(P)+) [EC:1.4.1.3]
K13577  
solute carrier family 25 (mitochondrial dicarboxylate transporter), member 10
K00025  
malate dehydrogenase [EC:1.1.1.37]
K01596  
phosphoenolpyruvate carboxykinase (GTP) [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)
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)

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