L-Tyrosine is a non-essential amino acid, meaning the human body can produce it, though it is also obtained through the diet. It is synthesized primarily in the liver from the essential amino acid phenylalanine, catalyzed by the enzyme phenylalanine hydroxylase. While it serves as a fundamental building block for nearly all human proteins, it is also chemically modified to create a variety of powerful signaling molecules.
Tyrosine’s Role as a Chemical Precursor
Tyrosine provides the foundational chemical structure for several classes of biologically active compounds. One significant pathway involves its conversion into catecholamines, a group of neurotransmitters and hormones. The process begins with tyrosine being converted into L-DOPA, which is then transformed sequentially into dopamine, norepinephrine, and finally epinephrine. These molecules are responsible for regulating mood, attention, and the body’s rapid “fight-or-flight” response to stress.
Tyrosine also serves as the raw material for thyroid hormones in the endocrine system. Specifically, tyrosine residues within the protein thyroglobulin are combined with iodine atoms to synthesize triiodothyronine (T3) and thyroxine (T4). These hormones are released by the thyroid gland and regulate the body’s overall metabolic rate and energy levels. Without sufficient tyrosine, the production of these metabolic regulators would be impaired.
A different anabolic fate for tyrosine leads to the production of melanin, the pigment responsible for coloring human skin, hair, and eyes. The enzyme tyrosinase initiates this process by converting tyrosine into dopaquinone. Melanin protects the underlying tissues from damage by absorbing harmful ultraviolet (UV) radiation from sunlight. The variation in human pigmentation is largely determined by the specific pathway taken after dopaquinone formation, leading to the synthesis of either reddish-yellow pheomelanin or brown-black eumelanin.
How Tyrosine is Broken Down
Tyrosine is also subject to a catabolic pathway primarily located in the liver, which breaks it down for energy production. This breakdown process is initiated by the enzyme tyrosine aminotransferase (TAT), which removes the amino group and converts tyrosine into p-hydroxyphenylpyruvate. This intermediate compound is then acted upon by 4-hydroxyphenylpyruvate dioxygenase, which results in the formation of homogentisic acid. This series of enzymatic steps destabilizes the tyrosine structure, preparing it for ring cleavage.
The next step is the cleavage of the aromatic ring structure, a process catalyzed by the enzyme homogentisate 1,2-dioxygenase. This reaction transforms homogentisic acid into maleylacetoacetate. The resulting maleylacetoacetate is then converted into fumarylacetoacetate through an isomerization reaction. The final step in the pathway involves the enzyme fumarylacetoacetate hydrolase.
This final enzyme hydrolyzes fumarylacetoacetate, splitting it into two end products: fumarate and acetoacetate. Fumarate can enter the tricarboxylic acid (Krebs) cycle for energy or conversion into glucose. Acetoacetate is a ketone body used as a source of energy or a precursor for fatty acid synthesis.
Inherited Disorders of Tyrosine Metabolism
Disruptions in the catabolic pathway, often caused by genetic mutations leading to enzyme deficiencies, result in a group of conditions known as inherited disorders of tyrosine metabolism. These defects cause the specific metabolite immediately preceding the blocked step to accumulate to toxic levels.
The most severe of these is Tyrosinemia Type I (HT1), which results from a deficiency of the final enzyme, fumarylacetoacetate hydrolase (FAH). This defect causes a buildup of toxic metabolites, including succinylacetone, which severely damages the liver and kidneys. Untreated infants may experience liver failure, kidney tubular dysfunction leading to rickets, and neurological crises, often requiring lifelong management with a low-tyrosine diet and the medication nitisinone.
A separate disorder, Alkaptonuria (AKU), is caused by a deficiency in the enzyme homogentisate 1,2-dioxygenase (HGD). This enzyme is responsible for cleaving the ring structure of homogentisic acid (HGA). The resulting accumulation of HGA is excreted in the urine, causing it to turn dark or black upon exposure to air, a characteristic symptom often seen in infancy. Over time, HGA metabolites accumulate in connective tissues, leading to ochronosis, a bluish-black pigmentation of cartilage and skin, which contributes to severe, early-onset arthritis in adults.
Tyrosinemia Type II (TYR II) involves a deficiency in the catabolic enzyme, tyrosine aminotransferase (TAT). This blockage prevents the initial breakdown of tyrosine, causing the amino acid itself to accumulate to high concentrations in the blood and tissues. The excess tyrosine forms crystals that deposit in the eyes, causing painful corneal ulcers and light sensitivity (photophobia). It also leads to thick, painful skin lesions on the palms and soles known as palmoplantar hyperkeratosis. Like HT1, this condition is managed with a strict dietary restriction of both tyrosine and phenylalanine.