Indoleamine 2,3-dioxygenase: Difference between revisions

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'''Indoleamine 2,3-dioxygenase''' (IDO or INDO EC 1.13.11.52) is an enzyme that catalyzes the oxidative cleavage of tryptophan to kynurenine. This enzyme is widely distributed in humans and other mammals and is involved in the immune response and the biosynthesis of nicotinamide adenine dinucleotide (NAD+).
{{DISPLAYTITLE:Indoleamine 2,3-dioxygenase}}


== Function ==
==Indoleamine 2,3-dioxygenase==
[[File:PDB_2d0t_EBI.jpg|thumb|right|300px|Crystal structure of Indoleamine 2,3-dioxygenase.]]


IDO is an immune checkpoint molecule in the sense that it is induced in various cell types at the tumor site by inflammatory stimuli, especially interferon gamma (IFNγ). The expression of IDO by tumors and antigen-presenting cells in the tumor microenvironment is known to cause local tryptophan depletion and high local kynurenine concentrations. This has multiple effects on the cells in the tumor environment.
'''Indoleamine 2,3-dioxygenase''' (IDO) is an enzyme that plays a crucial role in the metabolism of [[tryptophan]], an essential [[amino acid]]. It is involved in the kynurenine pathway, which is the primary route of tryptophan catabolism in mammals. IDO is of significant interest in the fields of [[immunology]] and [[cancer research]] due to its role in immune modulation and tumor immune evasion.


== Clinical significance ==
==Structure==
IDO is a heme-containing enzyme that catalyzes the oxidative cleavage of the indole ring of tryptophan, leading to the formation of [[N-formylkynurenine]]. The enzyme is composed of a single polypeptide chain and contains a heme prosthetic group that is essential for its catalytic activity. The crystal structure of IDO reveals a complex architecture that facilitates its interaction with tryptophan and other substrates.


IDO is thought to play a role in various disease states such as cancer, chronic infections, and autoimmune diseases. IDO is also thought to be involved in the pathology of diseases of the nervous system, including Alzheimer's disease, Huntington's disease, and multiple sclerosis.
==Function==
IDO is primarily expressed in [[dendritic cells]], [[macrophages]], and other [[antigen-presenting cells]]. It is induced by pro-inflammatory cytokines such as [[interferon-gamma]] (IFN-_). The enzyme's activity leads to the depletion of tryptophan in the local environment, which can suppress the proliferation of [[T cells]] and promote immune tolerance. This mechanism is particularly important in maintaining [[maternal-fetal tolerance]] during pregnancy and in preventing autoimmunity.


== See also ==
==Role in Disease==
IDO has been implicated in various diseases, including [[cancer]], [[chronic infections]], and [[autoimmune disorders]]. In cancer, tumor cells can exploit IDO to create an immunosuppressive microenvironment, allowing them to evade immune surveillance. Inhibitors of IDO are being investigated as potential therapeutic agents in cancer immunotherapy.


* [[Tryptophan]]
==Clinical Significance==
* [[Kynurenine]]
The modulation of IDO activity has therapeutic potential in several clinical settings. Inhibiting IDO can enhance anti-tumor immunity and improve the efficacy of [[checkpoint inhibitors]] in cancer treatment. Conversely, enhancing IDO activity may be beneficial in conditions where immune suppression is desired, such as in [[organ transplantation]] or [[autoimmune diseases]].
* [[Interferon gamma]]
* [[Immune checkpoint]]
* [[Alzheimer's disease]]
* [[Huntington's disease]]
* [[Multiple sclerosis]]


== References ==
==Related pages==
* [[Tryptophan metabolism]]
* [[Kynurenine pathway]]
* [[Immune tolerance]]
* [[Cancer immunotherapy]]


<references />
== External links ==
* [https://www.ncbi.nlm.nih.gov/gene/3620 Indoleamine 2,3-dioxygenase] at the US National Library of Medicine Medical Subject Headings (MeSH)
[[Category:EC 1.13.11]]
[[Category:Human proteins]]
[[Category:Immune system]]
[[Category:Enzymes]]
[[Category:Enzymes]]
 
[[Category:Immunology]]
{{stub}}
[[Category:Cancer research]]

Latest revision as of 06:50, 16 February 2025


Indoleamine 2,3-dioxygenase[edit]

File:PDB 2d0t EBI.jpg
Crystal structure of Indoleamine 2,3-dioxygenase.

Indoleamine 2,3-dioxygenase (IDO) is an enzyme that plays a crucial role in the metabolism of tryptophan, an essential amino acid. It is involved in the kynurenine pathway, which is the primary route of tryptophan catabolism in mammals. IDO is of significant interest in the fields of immunology and cancer research due to its role in immune modulation and tumor immune evasion.

Structure[edit]

IDO is a heme-containing enzyme that catalyzes the oxidative cleavage of the indole ring of tryptophan, leading to the formation of N-formylkynurenine. The enzyme is composed of a single polypeptide chain and contains a heme prosthetic group that is essential for its catalytic activity. The crystal structure of IDO reveals a complex architecture that facilitates its interaction with tryptophan and other substrates.

Function[edit]

IDO is primarily expressed in dendritic cells, macrophages, and other antigen-presenting cells. It is induced by pro-inflammatory cytokines such as interferon-gamma (IFN-_). The enzyme's activity leads to the depletion of tryptophan in the local environment, which can suppress the proliferation of T cells and promote immune tolerance. This mechanism is particularly important in maintaining maternal-fetal tolerance during pregnancy and in preventing autoimmunity.

Role in Disease[edit]

IDO has been implicated in various diseases, including cancer, chronic infections, and autoimmune disorders. In cancer, tumor cells can exploit IDO to create an immunosuppressive microenvironment, allowing them to evade immune surveillance. Inhibitors of IDO are being investigated as potential therapeutic agents in cancer immunotherapy.

Clinical Significance[edit]

The modulation of IDO activity has therapeutic potential in several clinical settings. Inhibiting IDO can enhance anti-tumor immunity and improve the efficacy of checkpoint inhibitors in cancer treatment. Conversely, enhancing IDO activity may be beneficial in conditions where immune suppression is desired, such as in organ transplantation or autoimmune diseases.

Related pages[edit]