Indoleamine 2,3-dioxygenase

Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO EC 1.13.11.52) is an is_associated_with::enzyme that in humans is encoded by the IDO1 is_associated_with::gene. This enzyme catalyzes the degradation of the essential amino acid is_associated_with::L-tryptophan to is_associated_with::N-formylkynurenine.

Function
Indoleamine 2,3-dioxygenase is the first and rate-limiting enzyme of is_associated_with::tryptophan is_associated_with::catabolism through is_associated_with::kynurenine pathway, thus causing depletion of tryptophan which can cause halted growth of microbes as well as is_associated_with::T cells.

IDO is an is_associated_with::immune checkpoint molecule in the sense that it is an is_associated_with::immunomodulatory enzyme produced by some alternatively activated is_associated_with::macrophages and other immunoregulatory cells (also used as an immune subversion strategy by many tumors). is_associated_with::Interferon-gamma has an antiproliferative effect on many tumor cells and inhibits intracellular pathogens such as Toxoplasma and chlamydia, at least partly because of the induction of indoleamine 2,3-dioxygenase.

Clinical significance
It has been shown that IDO permits tumor cells to escape the immune system by depletion of L-Trp in the microenvironment of cells. A wide range of human cancers such as prostatic, colorectal, pancreatic, cervical, gastric, ovarian, head, lung, etc. overexpress human IDO (hIDO).

Inhibitors
is_associated_with::Norharmane, via inhibition of indoleamine 2,3-dioxygenase exerts neuroprotective properties by suppressing is_associated_with::kynurenine neurotoxic metabolites such as is_associated_with::quinolinic acid, 3-hydroxy-kynurenine and is_associated_with::nitric oxide synthase. is_associated_with::Rosmarinic acid inhibits the expression of indoleamine 2,3-dioxygenase via its is_associated_with::cyclooxygenase-inhibiting properties. is_associated_with::COX-2 inhibitors down-regulate indoleamine 2,3-dioxygenase, leading to a reduction in is_associated_with::kynurenine levels as well as reducing proinflammatory cytokine activity. Alpha-Methyl-Tryptophan also inhibits indoleamine dioxygenase.