Entry
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
Drug
D00218 Acetazolamide (JP19/USP/INN)
D00652 Brinzolamide (JAN/USP/INN)
D00653 Dorzolamide hydrochloride (JP19/USP)
D00655 Methazolamide (JAN/USP/INN)
D01196 Acetazolamide sodium (JAN)
D03845 Sezolamide hydrochloride (USAN)
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
10991 SLC38A3; sodium-coupled neutral amino acid transporter 3 [KO:K13576 ]
1468 SLC25A10; mitochondrial dicarboxylate carrier isoform 2 [KO:K13577 ]
27165 GLS2; glutaminase liver isoform, mitochondrial isoform 1 precursor [KO:K01425 ] [EC:3.5.1.2 ]
2744 GLS; glutaminase kidney isoform, mitochondrial isoform 1 precursor [KO:K01425 ] [EC:3.5.1.2 ]
2746 GLUD1; glutamate dehydrogenase 1, mitochondrial isoform a precursor [KO:K00261 ] [EC:1.4.1.3 ]
2747 GLUD2; glutamate dehydrogenase 2, mitochondrial precursor [KO:K00261 ] [EC:1.4.1.3 ]
476 ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform a [KO:K01539 ] [EC:7.2.2.13 ]
477 ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 precursor [KO:K01539 ] [EC:7.2.2.13 ]
478 ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform 1 [KO:K01539 ] [EC:7.2.2.13 ]
480 ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 isoform 1 [KO:K01539 ] [EC:7.2.2.13 ]
481 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
482 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform 1 [KO:K01540 ]
483 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
486 FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform 1 [KO:K01538 ]
5106 PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform 1 precursor [KO:K01596 ] [EC:4.1.1.32 ]
6550 SLC9A3; sodium/hydrogen exchanger 3 isoform 1 precursor [KO:K12040 ]
8671 SLC4A4; electrogenic sodium bicarbonate cotransporter 1 isoform 1 [KO:K13575 ]
Compound
Reference
Authors
Koeppen BM
Title
The kidney and acid-base regulation.
Journal
Reference
Authors
Boron WF
Title
Acid-base transport by the renal proximal tubule.
Journal
Reference
Authors
Hayashi M
Title
Physiology and pathophysiology of acid-base homeostasis in the kidney.
Journal
Reference
Authors
Wagner CA, Kovacikova J, Stehberger PA, Winter C, Benabbas C, Mohebbi N
Title
Renal acid-base transport: old and new players.
Journal
Reference
Authors
Fry AC, Karet FE
Title
Inherited renal acidoses.
Journal
Reference
Authors
Pereira PC, Miranda DM, Oliveira EA, Silva AC
Title
Molecular pathophysiology of renal tubular acidosis.
Journal
Reference
Authors
Igarashi T, Sekine T, Inatomi J, Seki G
Title
Unraveling the molecular pathogenesis of isolated proximal renal tubular acidosis.
Journal
Reference
Authors
Alper SL
Title
Genetic diseases of acid-base transporters.
Journal
Reference
Authors
Unwin RJ, Capasso G
Title
The renal tubular acidoses.
Journal
Reference
Authors
Rodriguez-Soriano J
Title
New insights into the pathogenesis of renal tubular acidosis--from functional to molecular studies.
Journal
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
Reference
Authors
Curthoys NP
Title
Role of mitochondrial glutaminase in rat renal glutamine metabolism.
Journal
Related pathway
KO pathway