Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway

The kynurenine pathway of tryptophan metabolism converts the amino acid tryptophan into a number of biologically active metabolites. The first and rate-limiting step in this pathway is the conversion of tryptophan to N-formylkynurenine and until recently this reaction was thought to he performed by either of two enzymes, tryptophan 2,3-dioxygenase and indoleaminc 2,3-dioxygenase. A third enzyme, indoleamine 2,3-dioxygenase-2, indoleamine 2,3-dioxygenase-like protein or proto-indoleamine 2,3-dioxygenase (1DO2, IDO-2, INDOLI or proto-IDO). with this activity recently has been described. The gene encoding IDO2 is adjacent and structurally similar to the indoleamine 2,3-dioxygenase gene and both mouse genes use multiple promoters to express transcripts with alternate S' exons. The IDO2 protein is expressed in the marine kidney, liver, male and female reproductive system. The two IDO enzymes can utilise a similar range of substrates, however they differ in their selectivity for some inhibitors. The selective inhibition of 1DO2 by 1-methyl-n-tryptophan suggests that IDO2 activity may have a role in the inhibition of imnnrne responses to tumours. (C) 2009 Elsevier Ltd. All rights reserved.