{"id":21883,"date":"2019-08-12T07:15:07","date_gmt":"2019-08-12T07:15:07","guid":{"rendered":"https:\/\/wames.org.uk\/cms-english\/?p=21883"},"modified":"2019-08-12T07:15:07","modified_gmt":"2019-08-12T07:15:07","slug":"the-ido-metabolic-trap-hypothesis-for-the-etiology-of-me-cfs","status":"publish","type":"post","link":"https:\/\/wames.org.uk\/cms-english\/the-ido-metabolic-trap-hypothesis-for-the-etiology-of-me-cfs\/","title":{"rendered":"The IDO metabolic trap hypothesis for the etiology of ME\/CFS"},"content":{"rendered":"

The IDO metabolic trap hypothesis for the etiology of ME\/CFS,<\/a> by Alex A Kashi, Ronald W Davis, Robert D Phair in<\/span> Diagnostics <\/em>Vol 9, #3, p 82 [July 26, 2019]<\/h3>\n

 <\/p>\n

Research abstract:<\/strong><\/h3>\n
\"\"<\/a>

Dr Robert Phair<\/p><\/div>\n

Myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) is a debilitating noncommunicable disease brandishing an enormous worldwide disease burden with some evidence of inherited genetic risk.<\/p>\n

Absence of measurable changes in patients’ standard blood work has necessitated ad hoc symptom-driven therapies and a dearth of mechanistic hypotheses regarding its etiology and possible ! cure.<\/p>\n

A new hypothesis, the indolamine-2,3-dioxygenase (IDO) metabolic trap, was developed and formulated as a mathematical model. The historical occurrence of ME\/CFS outbreaks is a singular feature of the disease and implies that any predisposing genetic mutation must be common.<\/p>\n

A database search for common damaging mutations in human enzymes produces 208 hits, including IDO2 with four such mutations. Non-functional IDO2, combined with well-established substrate inhibition of IDO1 and kinetic asymmetry of the large neutral amino acid transporter, LAT1, yielded a mathematical model of tryptophan metabolism that displays both physiological and pathological steady-states. Escape from the pathological one requires an exogenous perturbation.<\/p>\n

This model also identifies a critical point in cytosolic tryptophan abundance beyond which descent into the pathological steady-state is inevitable. If, however, means can be discovered to return cytosolic tryptophan below the critical point, return to the normal physiological steady-state is assured. Testing this hypothesis for any cell type requires only labelled tryptophan, a means to measure cytosolic tryptophan and kynurenine, and the standard tools of tracer kinetics.<\/p>\n

Comment:<\/strong><\/p>\n

The IDO Metabolic Trap<\/a> July 26, 2019
\nBy Christopher Armstrong, PhD<\/p>\n","protected":false},"excerpt":{"rendered":"

The IDO metabolic trap hypothesis for the etiology of ME\/CFS, by Alex A Kashi, Ronald W Davis, Robert D Phair in Diagnostics Vol 9, #3, p 82 [July 26, 2019]   Research abstract: Myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) is a … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[5248,1190,5250,5246,4360,5251,5247,1885,5244,1920,5245,5249],"class_list":["post-21883","post","type-post","status-publish","format-standard","hentry","category-news","tag-3-dioxygenase","tag-aetiology","tag-alex-a-kashi","tag-bistability","tag-dr-robert-phair","tag-ido-metabolic-trap-hypothesis","tag-indoleamine-2","tag-kynurenine-pathway","tag-mathematical-model","tag-prof-ronald-w-davis","tag-substrate-inhibition","tag-tryptophan-metabolism"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p5qkYK-5GX","_links":{"self":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/21883","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/comments?post=21883"}],"version-history":[{"count":5,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/21883\/revisions"}],"predecessor-version":[{"id":22072,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/21883\/revisions\/22072"}],"wp:attachment":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/media?parent=21883"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/categories?post=21883"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/tags?post=21883"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}