Abstract:
Patients suffering from autoimmune disease, cancer or chronic inflammatory diseases mostly suffer from severe “complications” of their underlying illness, like weight loss, physical inefficiency, immunodeficiency, anemia, chronic fatigue, mood disorders or even depression. All these symptoms can severely impair the quality of life of patients. The percentage of patients with chronic diseases complaining about poor quality of life is high, irrespective of their underlying disease.
Interestingly, most patients suffering from chronic inflammatory disease have a strongly disturbed tryptophan metabolism. Within cellular immune response the essential amino acid tryptophan is degraded by the enzyme indoleamine-2,3-dioxygenase (IDO), leading to lowered tryptophan serum/plasma concentrations and increased levels of tryptophan catabolites like kynurenine. Tryptophan is not only necessary for the growth and proliferation of various cells as well as pathogens, it is also the precursor of the important neurotransmitters serotonin (5-hydroxytryptamin) and nicotinamide adenine dinucleotide (NAD). Increased tryptophan degradation within chronic inflammatory cascades thus leads to a diminished tryptophan availability, which might not only decrease the immunoresponsiveness of patients, but may also influence their mood, physical strength and haematopoiesis.
In fact, immune-mediated tryptophan degradation is supposed to contribute importantly to the development of fatigue, weight loss, and neuropsychiatric disorders. This review provides an overview, how enhanced IDO-activation might contribute to the development of various symptoms impairing the quality of life of patients with chronic disease.
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Abbreviations
- ACMSA:
-
aminocarboxymuconic semialdehyde
- ATP:
-
adenosine triphosphate
- GCH:
-
guanine triphosphate cylohydrolase I
- HIV:
-
human immunodeficiency virus infection
- IDO:
-
indoleamine 2,3-dioxygenase
- IFN-γ:
- INDOL 1:
-
indoleamine-pyrrole 2,3-dioxygenase-like 1
- Kyn/trp:
-
kynurenine to tryptophan ratio
- LPS:
-
lipopolysaccharide
- NAD:
-
nicotinamide adenine dinucleotide
- TDO:
-
tryptophan pyrrolase
- Th1 type immune response:
-
T-helper cell type 1 immune response
- TNF-α:
-
tumor necrosis factor-α
- 5-HT:
-
5-hydroxytryptamin (= serotonin)
- 1-MT:
-
1-methyl-tryptophan
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Appendix
Appendix
Key features of tryptophan:
-
Tryptophan is an essential amino acid.
-
Tryptophan is degraded by three enzymes: tryptophan dioxygenase (TDO), indoleamine-2,3-dioxygenase (IDO) and indoleamine-pyrrole 2,3-dioxygenase-like 1 (INDOL 1).
-
Tryptophan is the precursor of serotonin and nicotinamide dinucleotide.
-
Tryptophan deprivation represents an important mechanism to inhibit the growth of various pathogens and cells.
-
Enhanced tryptophan degradation takes place during cellular immune response.
-
Immune-mediated tryptophan degradation might play an important role in the development of several symptoms frequently encountered in patients with chronic disease: fatigue, weight loss, anemia, neuropsychiatric complications.
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Fuchs, D., Schroecksnadel, K., Neurauter, G., Bellmann-Weiler, R., Ledochowski, M., Weiss, G. (2010). Quality of Life and Tryptophan Degradation. In: Preedy, V.R., Watson, R.R. (eds) Handbook of Disease Burdens and Quality of Life Measures. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78665-0_119
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