Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells
to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid
with a polar side group. The word "tyrosine" is from the Greek tyros, meaning cheese, as
it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein
from cheese. It is called tyrosyl when referred to as a functional group or side chain.
Functions Aside from being a proteinogenic amino acid,
tyrosine has a special role by virtue of the phenol functionality. It occurs in proteins
that are part of signal transduction processes. It functions as a receiver of phosphate groups
that are transferred by way of protein kinases. Phosphorylation of the hydroxyl group changes
the activity of the target protein. A tyrosine residue also plays an important
role in photosynthesis. In chloroplasts, it acts as an electron donor in the reduction
of oxidized chlorophyll. In this process, it undergoes deprotonation of its phenolic
OH-group. This radical is subsequently reduced in the photosystem II by the four core manganese
clusters. Dietary sources
Tyrosine, which can also be synthesized in the body from phenylalanine, is found in many
high-protein food products such as chicken, turkey, fish, milk, yogurt, cottage cheese,
cheese, peanuts, almonds, pumpkin seeds, sesame seeds, soy products, lima beans, avocados,
and bananas. Biosynthesis
In plants and most microorganisms, tyr is produced via prephenate, an intermediate on
the shikimate pathway. Prephenate is oxidatively decarboxylated with retention of the hydroxyl
group to give p-hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen
source to give tyrosine and α-ketoglutarate. Mammals synthesize tyrosine from the essential
amino acid phenylalanine, which is derived from food. The conversion of phe to tyr is
catalyzed by the enzyme phenylalanine hydroxylase, a monooxygenase. This enzyme catalyzes the
reaction causing the addition of a hydroxyl group to the end of the 6-carbon aromatic
ring of phenylalanine, such that it becomes tyrosine.
Metabolism
Phosphorylation and sulfation Some of the tyrosine residues can be tagged
with a phosphate group by protein kinases. In its phosphorylated form, tyrosine is called
phosphotyrosine. Tyrosine phosphorylation is considered to be one of the key steps in
signal transduction and regulation of enzymatic activity. Phosphotyrosine can be detected
through specific antibodies. Tyrosine residues may also be modified by the addition of a
sulfate group, a process known as tyrosine sulfation. Tyrosine sulfation is catalyzed
by tyrosylprotein sulfotransferase. Like the phosphotyrosine antibodies mentioned above,
antibodies have recently been described that specifically detect sulfotyrosine.
Precursor to neurotransmitters and hormones In dopaminergic cells in the brain, tyrosine
is converted to l-dopa by the enzyme tyrosine hydroxylase. TH is the rate-limiting enzyme
involved in the synthesis of the neurotransmitter dopamine. Dopamine can then be converted into
the catecholamines norepinephrine and epinephrine. The thyroid hormones triiodothyronine and
thyroxine in the colloid of the thyroid also are derived from tyrosine.
Precursor to alkaloids The latex of Papaver somniferum, the opium
poppy, has been shown to convert tyrosine into the alkaloid morphine and the bio-synthetic
pathway has been established from tyrosine to morphine by using Carbon-14 radio-labelled
tyrosine to trace the in-vivo synthetic route. Mescaline producing cactus bio-synthesize
tyrosine into mescaline when injected with it.
Precursor to natural phenols Tyrosine ammonia lyase is an enzyme in the
natural phenols biosynthesis pathway. It transforms L-tyrosine into p-coumaric acid.
Precursor to pigments Tyrosine is also the precursor to the pigment
melanin. Role in Coenzyme Q10 synthesis
Tyrosine is needed to synthesize the benzoquinone structure which forms part of coenzyme q10.
Degradation
The decomposition of L-tyrosine begins with an α-ketoglutarate dependent transamination
through the tyrosine transaminase to para-hydroxyphenylpyruvate. The positional description para, abbreviated
p, mean that the hydroxyl group and side chain on the phenyl ring are across from each other.
The next oxidation step catalyzes by p-hydroxylphenylpyruvate-dioxygenase and splitting off CO2 homogentisate. In order
to split the aromatic ring of homogentisate, a further dioxygenase, homogentistate-oxygenase
is required. Thereby, through the incorporation of a further O2 molecule, maleylacetoacetate
is created. Fumarylacetate is created maleylacetoacetate-cis-trans-isomerase
through rotation of the carboxyl group created from the hydroxyl group via oxidation. This
cis-trans-isomerase contains glutathione as a coenzyme. Fumarylacetoacetate is finally
split by the enzyme fumarylacetoacetate hydrolase through the addition of a water molecule.
Thereby fumarate and acetoacetate are liberated. Acetoacetate is a ketone body, which is activated
with succinyl-CoA, and thereafter it can be converted into acetyl-CoA, which in turn can
be oxidized by the citric acid cycle or be used for fatty acid synthesis.
Phloretic acid is also a urinary metabolite of tyrosine in rats.
Betaines
Ortho- and meta-tyrosine
Three structural isomers of L-tyrosine are known. In addition to common amino acid L-tyrosine,
which is the para isomer, there are two additional regioisomers, namely meta-tyrosine and ortho-tyrosine,
that occur in nature. The m-tyr and o-tyr isomers, which are rare, arise through non-enzymatic
free-radical hydroxylation of phenylalanine under conditions of oxidative stress.
m-Tyrosine and analogues have shown application in Parkinson's Disease, Alzheimer's disease
and arthritis. Medical use
Tyrosine is a precursor to neurotransmitters and increases plasma neurotransmitter levels
but has little if any effect on mood. The effect on mood is more noticeable in humans
subjected to stressful conditions. A number of studies have found tyrosine to
be useful during conditions of stress, cold, fatigue, loss of a loved one such as in death
or divorce, prolonged work and sleep deprivation, with reductions in stress hormone levels,
reductions in stress-induced weight loss seen in animal trials, improvements in cognitive
and physical performance seen in human trials; however, because tyrosine hydroxylase is the
rate-limiting enzyme, effects are less significant than those of L-DOPA.
Tyrosine does not seem to have any significant effect on mood, cognitive or physical performance
in normal circumstances. A daily dosage for a clinical test supported in the literature
is about 100 mg/kg for an adult, which amounts to about 6.8 grams at 150 lbs. The usual
dosage amounts to 500–1500 mg per day. It is not recommended to exceed 12000 mg
per day. See also
Albinism Alkaptonuria
Betalain Iodinated tyrosine derivatives
Tyramine Tyrosine sulfation
Tyrosinemia Pauly reaction
References
External links Tyrosine MS Spectrum
Tyrosine metabolism Phenylalanine and tyrosine biosynthesis
Phenylalanine, Tyrosine, and tryptophan biosynthesis Tyrosine in the ChemIDplus database