Introduction
Tryptophan is an amino acid required for normal infant growth and the formation and maintenance of the body's proteins, enzymes, neurotransmitters, and muscles. The tryptophan metabolic pathway is a significant network connecting various systems, including the neurological system's immunological inflammatory response, which involves inflammation, stress, the kynurenine pathway, and neurotransmission.
Enzymes or products of the tryptophan metabolic process are related to neurological disorders like epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, autism, and psychiatric disorders (depression, anxiety, and bipolar disorder).
What Is Tryptophan?
Tryptophan is an important amino acid that is needed in the production of proteins. People must obtain it because the human body does not produce it through their diet. Tryptophan is found in animal products such as chicken and fish and plant foods such as nuts and soybeans.
Tryptophan is used by the body to help produce melatonin and serotonin. Melatonin aids in regulating the sleep-wake cycle, whereas serotonin is known to aid in regulating mood, appetite, pain, and sleep. The liver can also use tryptophan to make niacin (vitamin B3), which is required for DNA synthesis and energy metabolism.
After consuming tryptophan, the tissues convert some of it to 5-HTP (5-hydroxytryptophan), which is then converted into serotonin, a neurotransmitter. Tryptophan is also converted by the body to NAD (nicotinamide adenine dinucleotide).
How Tryptophan Is Metabolized in the Human Body?
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In humans, tryptophan is metabolized via the kynurenine or serotonin pathways resulting in bioactive metabolites. 90 % of kynurenine pathway breakdown occurs in the liver via tryptophan 2,3-dioxygenase. It involves the conversion of tryptophan to kynurenine.
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Indoleamine 2,3-dioxygenase in the central nervous system, gastrointestinal tract, and liver degrade the remaining kynurenine. Kynurenine aminotransferase enzymes convert it to kynurenic acid. It can also be transformed into quinolinic acid and is then transformed into NAD+. Alternatively, kynurenine is transformed into 3-hydroxykynurenine and then into xanthurenic acid.
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Tryptophan is converted to 5-hydroxy tryptophan (5-HTP) in the serotonin pathway by tryptophan hydroxylase 1 (in enterochromaffin cells) or tryptophan hydroxylase 2. Serotonin is formed when 5-HTP is decarboxylated. Serotonin can be further converted to generate melatonin or reduced to 5-hydroxy indole acetic acid by monoamine oxidase (MAO), which is eliminated in the urine.
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Tryptophan is processed by intestinal microbes into indole and indole compounds. Microbes produce a variety of enzymes that use tryptophan.
What Are Tryptophan Disorders?
Tryptophan disorders are a group of conditions that impair tryptophan metabolism. Depending on the underlying genetic cause and the impacted metabolic pathways, the specific symptoms and extent of tryptophan disorders may vary.
What Are the Examples of Tryptophan Disorders?
1. Hartnup Disease
It is a rare hereditary illness that causes poor tryptophan absorption and reabsorption in the gastrointestinal tract and kidneys. It can cause tryptophan deficiency, disrupting serotonin and other essential chemical production. Skin rashes, neurological problems, and behavioral disorders are the possible symptoms of Hartnup disease.
According to estimates, one in 30,000 people suffers from Hartnup syndrome. Mutations within the SLC6A19 gene lead to Hartnup disease. These gene mutations in the SLC6A19 gene result in synthesizing a protein (B0AT1) with reduced activity. As a result, certain amino acids cannot be absorbed by cells and are excreted from the body as waste. People with this Hartnup syndrome have low levels of specific amino acids and vitamins because these amino acids are eliminated from the body without being utilized.
Hartnup disease patients exhibit elevated levels of different amino acids in their urine. However, some persons with Hartnup illness experience other symptoms, such as skin rashes, difficulties coordinating movements, and psychiatric symptoms, such as depression or psychosis. These episodes are usually brief and are brought on by illness, stress, a nutrient-deficient diet, or fever. These characteristics usually disappear as the trigger is removed.
2. Tryptophan Malabsorption
This condition affects tryptophan absorption from foods. Mutations in the SLC6A19 gene, which codes for a transporter protein involved in tryptophan absorption in the intestines, cause it. Reduced tryptophan levels can lead to a lack of serotonin and other tryptophan-derived metabolites. Gastrointestinal problems, skin abnormalities, intellectual impairment, and mental disorders are possible symptoms of tryptophan malabsorption.
3. Deficiency of Tryptophan Hydroxylase
The tryptophan hydroxylase enzyme converts tryptophan to serotonin. A lack of this enzyme can result in low serotonin levels and can cause various neurological and mental symptoms, such as depression, anxiety, and problems with sleeping.
4. Serotonin Syndrome
Although not a tryptophan disease, serotonin syndrome can occur when the body has an excess of serotonin. It may occur due to tryptophan disorders. This can occur due to interactions between drugs or supplements that boost serotonin levels. Agitation, confusion, a high heart rate, and, in severe situations, seizures or coma are the possible symptoms.
5. Hypertryptophanemia
It is an extremely rare autosomal recessive metabolic condition characterized by an abnormally high concentration of tryptophan in the blood, symptoms, and increased tryptophan in urine.
What Are the Symptoms Associated With Tryptophan Disorders?
The symptoms associated with tryptophan disorders may vary depending on the underlying cause. The common symptoms seen in people with tryptophan disorders are the following.
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Affected people may be more sensitive to sunlight, leading to skin rashes or a sunburn-like reaction.
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Some people may experience neurological symptoms like decreased muscular coordination, seizures, or behavioral abnormalities.
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Digestive disorders such as stomach pain, diarrhea, and vomiting.
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Some people may have psychiatric symptoms such as depression, anxiety, or psychosis.
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Excessive urinary tryptophan excretion can lead to niacin insufficiency, producing symptoms such as dermatitis, vomiting, and dementia.
What Are the Treatment Options Available for Tryptophan Disorders?
Treatment for tryptophan disorders is determined based on the severity of the condition and its symptoms. It includes dietary changes, tryptophan or other nutritional supplementation, and management of related symptoms. Individuals with these conditions and their families are frequently advised to seek genetic counseling better to understand their familial inheritance patterns and any possible risks.
Conclusion
Tryptophan disorders are uncommon, and most people do not exhibit any specific symptoms that might allow them to be diagnosed early. If someone suspects any issues related to tryptophan metabolism, or experiences any symptoms, then it will be better to consult a medical professional for an accurate diagnosis and appropriate management.
