Table of Contents
Tyrosine is one of the nonessential amino acids that the body uses to synthesize polypeptides or proteins. It has a polar side group and is produced when the body processes the amino acid phenylalanine. It is essential in producing several neurotransmitters like epinephrine, dopamine, and norepinephrine. They also help in producing melanin, which is the pigment present in the skin and hair. It is also used in the regulation of several hormones including the thyroid, pituitary and the adrenal.
The phenol group in the structure of tyrosine affects the different functions it can serve. It can serve as a part of the signal transduction processes. It can function as a receiver of phosphate groups where the attachment is catalyzed by protein kinases. When the phenol group is phosphorylated, the activity of the target protein will be affected.
In plants, tyrosine plays a major role in photosynthesis. It acts as an electron donor in the reduction of oxidized chlorophyll. In the process, the hydroxyl group of the side chain is lost.
Tyrosine can be metabolized to produce the different neurotransmitters. In the first steps of the metabolic process, L-tyrosine is converted to levodopa using tyrosine hydroxylase as enzyme and tetrahydropyridine as a cofactor. The levodopa is further decarboxylated to produce dopamine using Dopa decarboxylase as an enzyme.
The dopamine can then be further oxidized using Dopamine beta-hydroxylase (dopamine beta-monooxygenase). The end product of hydroxylation is Noradrenaline. Noradrenaline can then be methylated using Phenylethanolamine N-methyltransferase. The end product of this step is adrenaline.
Levodopa or L-DOPA is the precursor of the neurotransmitter dopamine, norepinephrine, and epinephrine. It readily mediates neurotrophic factors released by the brain and the central nervous system. It is sometimes produced as a psychoactive drug. It can cross the blood-brain barrier which dopamine cannot do. L-DOPA is being administered to patients with Parkinson’s disease and dopamine-responsive dystonia to increase the dopamine concentration in the patient.
Dopamine is a neurotransmitter that plays a big role in reward-motivated behavior. Most types of rewards cause an increase in the release of dopamine in the brain. It also functions as a local chemical messenger. It sometimes inhibits release of noradrenaline and acts as vasodilators.
Norepinephrine or noradrenaline is another neurotransmitter produced by the metabolism of tyrosine. It functions mainly to mobilize the brain and body for action. Its release is lowest during sleep and rises upon waking up. Its release is related to the fight or flight response of the body. Norepinephrine is responsible for increasing arousal and alertness.
Adrenaline or epinephrine is a hormone or neurotransmitter produced by neurons and the adrenal gland. It plays a major role in flight or flight response by increasing blood flow in the body. In the process, the body becomes more active, the pupil dilates and blood sugar increases.
Figure 2. Neurotransmitters produced in the metabolism of tyrosine. (Prepared by Mark Xavier Bailon)
Tyrosine is a Precursor of Thyroid Hormones
Thyroid hormones are tyrosine-based hormones produced by the thyroid gland. They function primarily for regulation of metabolism. These hormones include triiodothyronine (T3) and thyroxine (T4).
These two hormones work to:
- increasing the basal metabolic rate
- affecting protein synthesis
- regulating bone growth
- increasing the body’s sensitivity to catecholamine like adrenaline
- being important in development and differentiation of cells of the body
- being responsible for regulating carbohydrate, fat and protein metabolism
- stimulating vitamin metabolism
Thyroxine and triiodothyronine are both produced by follicular cells of the thyroid gland. They regulated by the thyroid-stimulating hormone. Thyroxine is produced by a series of steps in the follicular cells.
First, the Na+/I– symporter transports two sodium ions across the basement membrane of the cell. Passing along with the sodium ions is an iodide. I– is then moved across the apical membrane into the colloid of the follicle. Iodide ion is then oxidized by thyroperoxidase. The tyrosyl residues of the thyroglobulin are then iodinated by thyroperoxidase. The iodinated thyroglobulin then binds to megalin for endocytosis back into the cell.
TSH from the adenohypophysis binds to the TSH receptor to stimulate endocytosis. The endocytosed vesicle then fuses with the lysosome of the follicular cell which eventually cleaves the thyroxine from the iodinated thyroglobulin.
Figure 3. Thyroid hormone production. (Häggström, Mikael (2014). “Medical gallery of Mikael Häggström 2014“. WikiJournal of Medicine 1)
Tyrosine Metabolism and Disease
One of the most common disorders related to tyrosine is tyrosinemia. It is a genetic disorder that is characterized by disruptions in the different steps in the break down of tyrosine. When untreated, the tyrosine and the by products of the whole process may build up in tissues leading to serious health problems.
Three types of tyrosinemia occur:
Type I tyrosinemia is the most severe of all the types of tyrosinemia. The signs and symptoms of this disorder show in the first few months of life. Infants with Type I Tyrosinemia fail to gain weight and grow. They experience poor food tolerance. Food rich in protein may cause diarrhea and vomiting. Infants also show yellowing of the skin and the white of the eyes. Eventually Type I tyrosinemia can lead to kidney and liver failure. Rickets or weakening of bones may also be experienced. The risk for liver cancer also increases. Untreated children often do not survive past age 10.
Type II tyrosinemia is a less severe type of tyrosinemia which affects the skin, eyes, and mental development. Signs and symptoms also show during early years of life. Symptoms include eye pain and redness, photophobia, painful skin on palms and sole of feet. Almost 50% of patients with this type of tyrosinemia have some degree of intellectual disability.
The rarest type of tyrosinemia is Type III. Features of this disorder include intellectual disability, seizures, and intermittent ataxia. Another type is transient tyrosinemia, which occurs in about 10% of newborns with temporarily elevated levels of tyrosine. The cause of transient tyrosinemia is not genetic. The cause of this type is Vitamin C deficiency or problems with liver enzymes due to premature birth.
The correct answers can be found below the referenced.
1. Which of the following is not produced by tyrosine metabolism?
- GABA (Gamma aminobutyric acid)
2. Which of the following types of tyrosinemia is not genetic in nature?
- Type I
- Type II
- Type III