Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irritable bowel syndrome (IBS) has been linked with abnormal serotonin functioning and immune activation. Tryptophan forms the substrate for serotonin biosynthesis, but it can alternatively be catabolized to kynurenine (Kyn) by the enzyme indoleamine 2,3-dioxygenase (IDO), the main inducer of which is interferon-gamma. The primary aim of this study was to test the hypothesis that IBS is associated with increased tryptophan (Trp) catabolism along the Kyn pathway due to increased IFN-gamma levels. Plasma Kyn, Trp and IFN-gamma levels were measured in 41 female IBS subjects and 33 controls. Indoleamine 2,3-dioxygenase activity was assessed using the Kyn to Trp ratio. Psychiatric co-morbidity was assessed using the Patient Health Questionnaire, and severity of IBS assessed using self-report ordinal scales. Irritable bowel syndrome subjects had increased Kyn concentrations compared with controls (P = 0.039) and there was a trend for Kyn:Trp to be increased in the IBS group (P = 0.09). There was a positive correlation between IBS severity and Kyn:Trp (r = 0.57, P < 0.001). Those with severe IBS symptoms had increased Kyn:Trp (P < 0.005) compared to those with less severe symptoms and controls, and were over twice as likely to have depression or anxiety compared to those with less severe IBS (RR = 2.2, 95% CI 1.2-3.9). No difference in IFN-gamma levels was observed between groups; however, IFN-gamma was positively correlated with Kyn:Trp in IBS (r = 0.58, P = 0.005) but not controls (r = 0.12, P = 0.5). Females with IBS have abnormal Trp catabolism. The Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have increased shunting of Trp along the Kyn pathway which contributes to the abnormal serotonergic functioning in this syndrome.
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PMID:Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon-gamma, severity of symptoms and psychiatric co-morbidity. 1901 30

The kynurenine pathway (KP) of L-tryptophan metabolism produces several neuroactive metabolites with an amino acid structure. These metabolites may play an important role in the pathophysiology of irritable bowel syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, AIDS-dementia complex, depression, epilepsy and the aging process. Modulation of the KP through inhibition or stimulation of enzyme synthesis and activity can be an alternative approach to traditional therapy. Furthermore, it may be responsible for the altered functioning of the enteric nervous system and the central nervous system. There is evidence that the KP is sensitive to changes in the concentration of many vitamins and minerals that play a crucial role as coenzymes and cofactors in the de novo synthesis of nicotinamide adenine dinucleotide coenzyme. A reduction in the availability of the active form of vitamin B6 (pyridoxal 5'-phosphate, PLP) is known to affect tryptophan hydroxylase, kynurenine aminotransferase and kynureninase (KYNU). Vitamin B2 deficiencies result in a reduction in the activity of the flavin adenine dinucleotide dependent enzyme, kynurenine 3-monooxygenase. Minerals are also responsible for the proper functioning of enzymes engaged in L-tryptophan metabolism. Mn(2+), Zn(2+), Co(2+) and Cu(2+) influence KYNU activity, and Mg(2+) regulates quinolinate phosphoribosyl transferase. Fe(2+) is responsible for the proper functioning of both indoleamine 2,3-dioxygenase and 3-hydroxy-anthranilic acid dioxygenase. Changes in the concentration of KP metabolites and in enzymatic activity have been found in many pathological states. Therefore, it is justifiable to regulate the concentration of certain kynurenines or enzymes in the KP which may provide a potential therapeutic target for the treatment of various health impairments. This review demonstrates the role of vitamin and mineral activity on the KP, which may have an effect on the proper functioning of the human organism. Surplus administration of vitamins did not elicit any beneficial effects on L-tryptophan metabolism. Whether a mineral surplus influences L-tryptophan metabolism is still not established. It seems that cofactor deficiencies influence the KP far more than surpluses.
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PMID:Overview of the role of vitamins and minerals on the kynurenine pathway in health and disease. 2701 Aug 91