RGD Reference Report - Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway. - Rat Genome Database

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Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway.

Authors: Dang, Y  Dale, WE  Brown, OR 
Citation: Dang Y, etal., Free Radic Biol Med. 2000 Feb 15;28(4):615-24.
RGD ID: 2290190
Pubmed: PMID:10719243   (View Abstract at PubMed)

Indoleamine 2,3-dioxygenase (IDO) reacts with either oxygen or superoxide and tryptophan (trp) or other indoleamines while tryptophan 2,3-dioxygenase (TDO) reacts with oxygen and is specific for trp. These enzymes catalyze the rate-limiting step in the kynurenine (KYN) pathway from trp to quinolinic acid (QA) with TDO in kidney and liver and IDO in many tissues, including brain where it is low but inducible. QA, which does not cross the blood-brain barrier, is an excitotoxin found in the CNS during various pathologies and is associated with convulsions. We proposed that HBO-induced convulsions result from increased flux through the KYN pathway via oxygen stimulation of IDO. To test this, TDO and IDO of liver and brain, respectively, of Sprague Dawley rats were assayed with oxygen from 0 to 6.2 atm HBO. TDO activity was appreciable at even 30 microM oxygen and rose steeply to a maximum at 40 microM. Conversely, IDO had almost no detectable activity at or below 100 microM oxygen and maximum activity was not reached until about 1150 microM. (Plasma contains about 215 microM oxygen and capillaries about 20 microM oxygen when rats breathe air.) KYN was 60% higher in brains of HBO-convulsed rats compared to rats breathing air. While the oxygen concentration inside cells of rats breathing air or HBO is not known precisely, it is clear that the rate-limiting, IDO-catalyzed step in the brain KYN pathway (but not liver TDO) can be greatly accelerated in rats breathing HBO.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ido1Rattryptophan catabolic process to kynurenine  IDA  RGD 
Tdo2Rattryptophan metabolic process  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ido1Ratamino acid binding  IDA  RGD 
Tdo2Ratamino acid binding  IDA  RGD 
Ido1Ratindoleamine 2,3-dioxygenase activity  IDA  RGD 
Ido1Ratoxygen binding  IDA  RGD 
Tdo2Ratoxygen binding  IDA  RGD 
Tdo2Rattryptophan 2,3-dioxygenase activity  IDA  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Objects Annotated

Genes (Rattus norvegicus)
Ido1  (indoleamine 2,3-dioxygenase 1)
Tdo2  (tryptophan 2,3-dioxygenase)

Genes (Mus musculus)
Ido1  (indoleamine 2,3-dioxygenase 1)
Tdo2  (tryptophan 2,3-dioxygenase)

Genes (Homo sapiens)
IDO1  (indoleamine 2,3-dioxygenase 1)
TDO2  (tryptophan 2,3-dioxygenase)


Additional Information