Catecholamine
Synthesis and Tyrosine
Catabolism
By ScholarRx
Updated December 14, 2020
access_time12 min
Learning Objectives (3)
After completing this brick, you will be able to:
● Describe the reactions associated with the catabolism of
catecholamines and serotonin.
● 1
● List the symptoms of pheochromocytoma and carcinoid syndrome
and the molecular basis of these symptoms.
● 2
● Describe the reactions and their sequence in the synthesis of
catecholamines from tyrosine and in the synthesis of serotonin from
tryptophan.
● 3
cableCASE CONNECTION
JA is a 46-year-old woman with hypertension that has been difficult to
control. She is taking four antihypertensive medications, but her blood
pressure in the office today is 152/96 mm Hg. “I still have those
episodic headaches and palpitations, and I know it’s summer but I
sure am sweating a lot. And yes, I am taking my medications, and no,
I’m not using cocaine. I get asked those questions all the time.” On
,exam, JA appears anxious. Her heart rate is 102/min; a recheck of her
blood pressure is 162/96 mm Hg. She has a fine tremor with
outstretched hands. Thyroid function tests are normal.
What diagnosis will you consider? What is the molecular basis for this
syndrome? Consider your answers as you read, and we’ll revisit at the
end of the brick.
GO TO CONCLUSION arrow_downward
Two Types of Monoamines
Neurotransmitters are the WiFi systems of the nervous system. These
molecules send signals from one neuron through a synapse to another
neuron, muscle cells, or some other structure. The major
neurotransmitters dopamine (DA), norepinephrine (NE), epinephrine
(E), and serotonin (5-HT) are all monoamines, and they are derived
from amino acids.
Monoamines can be divided into two groups based on their amino
acid precursors. The amino acid phenylalanine, which can be
converted to tyrosine, is responsible for the synthesis of
catecholamines, which include dopamine, norepinephrine, and
epinephrine. Dopamine is an important neurotransmitter in the brain,
where it is involved in reward pathways and motor function. It also
acts as a chemical messenger in the body, causing systemic effects
such as vasodilation and suppression of gastrointestinal (GI) motility.
Epinephrine and norepinephrine are neurotransmitters released by the
sympathetic nervous system to help stimulate the fight-or-flight
response.
,The monoamine serotonin is derived from a different amino acid
known as tryptophan. Serotonin regulates various functions such as
mood, appetite, sleep, blood clotting, and GI motility.
It is important to understand how monoamines are synthesized and
degraded because these pathways can be altered by many drugs and
disease processes.
Synthesis of Monoamines
Catecholamines are synthesized from the precursor phenylalanine,
which is an essential amino acid. Remember, “essential” means that
the body has no way of synthesizing of this amino acid, so it must
come from the diet. The enzyme phenylalanine hydroxylase uses
tetrahydrobiopterin (BH4) as a cofactor to convert phenylalanine to
tyrosine. The enzyme tyrosine hydroxylase also uses BH4 as a
cofactor and converts tyrosine to dihydroxyphenylalanine (DOPA).
This is the rate-limiting step in the synthesis of catecholamines.
After DOPA is formed, it can be converted to either melanin or
dopamine. The enzyme tyrosinase converts DOPA to melanin, which
is responsible for skin pigmentation. Alternatively, DOPA
decarboxylase converts DOPA to dopamine, and dopamine β-
hydroxylase converts dopamine to norepinephrine. The enzyme
phenylethanolamine-N-methyltransferase converts norepinephrine to
epinephrine. The steps of catecholamine synthesis are shown in
Figure 1. Note that the enzymes phenylalanine hydroxylase and
tyrosine hydroxylase both use BH4 as a cofactor, whereas the other
enzymes use different cofactors.
Serotonin is synthesized from tryptophan, which is another essential
amino acid. The enzyme tryptophan hydroxylase converts tryptophan
to 5‑hydroxytryptophan. This enzyme actually uses BH4, the same
, cofactor that phenylalanine hydroxylase and tyrosine hydroxylase use
to convert phenylalanine to tyrosine and tyrosine to DOPA. This is
obviously an important cofactor! The enzyme 5‑hydroxytryptophan
decarboxylase then converts 5‑hydroxytryptophan to serotonin. Note
that serotonin can be converted into melatonin, a hormone involved in
regulating sleep within the pineal gland. The steps of serotonin and
melatonin synthesis are shown in Figure 2.
IN-TRAINING
How do you feel about medical students using stimulant drugs to help
with their studies? What do you think the recently reported 15% usage
of stimulants in medical school? What are your thoughts on how to
raise awareness about this phenomenon? At the end of this brick,
please take a few minutes to read a first-person essay about a
medical student’s personal experience with using stimulant drugs and
reflect on a few thought questions.
READ MORE arrow_downward
Degradation of Monoamines
All monoamines are degraded by two main enzymes—catechol-O-
methyltransferase (COMT) and monoamine oxidase (MAO). Rather
than memorizing details of the degradative pathways, it is important
to recognize these enzyme names and the degradative products of
each neurotransmitter. The degradative product of dopamine is
homovanillic acid (HVA). The degradative product of both
Synthesis and Tyrosine
Catabolism
By ScholarRx
Updated December 14, 2020
access_time12 min
Learning Objectives (3)
After completing this brick, you will be able to:
● Describe the reactions associated with the catabolism of
catecholamines and serotonin.
● 1
● List the symptoms of pheochromocytoma and carcinoid syndrome
and the molecular basis of these symptoms.
● 2
● Describe the reactions and their sequence in the synthesis of
catecholamines from tyrosine and in the synthesis of serotonin from
tryptophan.
● 3
cableCASE CONNECTION
JA is a 46-year-old woman with hypertension that has been difficult to
control. She is taking four antihypertensive medications, but her blood
pressure in the office today is 152/96 mm Hg. “I still have those
episodic headaches and palpitations, and I know it’s summer but I
sure am sweating a lot. And yes, I am taking my medications, and no,
I’m not using cocaine. I get asked those questions all the time.” On
,exam, JA appears anxious. Her heart rate is 102/min; a recheck of her
blood pressure is 162/96 mm Hg. She has a fine tremor with
outstretched hands. Thyroid function tests are normal.
What diagnosis will you consider? What is the molecular basis for this
syndrome? Consider your answers as you read, and we’ll revisit at the
end of the brick.
GO TO CONCLUSION arrow_downward
Two Types of Monoamines
Neurotransmitters are the WiFi systems of the nervous system. These
molecules send signals from one neuron through a synapse to another
neuron, muscle cells, or some other structure. The major
neurotransmitters dopamine (DA), norepinephrine (NE), epinephrine
(E), and serotonin (5-HT) are all monoamines, and they are derived
from amino acids.
Monoamines can be divided into two groups based on their amino
acid precursors. The amino acid phenylalanine, which can be
converted to tyrosine, is responsible for the synthesis of
catecholamines, which include dopamine, norepinephrine, and
epinephrine. Dopamine is an important neurotransmitter in the brain,
where it is involved in reward pathways and motor function. It also
acts as a chemical messenger in the body, causing systemic effects
such as vasodilation and suppression of gastrointestinal (GI) motility.
Epinephrine and norepinephrine are neurotransmitters released by the
sympathetic nervous system to help stimulate the fight-or-flight
response.
,The monoamine serotonin is derived from a different amino acid
known as tryptophan. Serotonin regulates various functions such as
mood, appetite, sleep, blood clotting, and GI motility.
It is important to understand how monoamines are synthesized and
degraded because these pathways can be altered by many drugs and
disease processes.
Synthesis of Monoamines
Catecholamines are synthesized from the precursor phenylalanine,
which is an essential amino acid. Remember, “essential” means that
the body has no way of synthesizing of this amino acid, so it must
come from the diet. The enzyme phenylalanine hydroxylase uses
tetrahydrobiopterin (BH4) as a cofactor to convert phenylalanine to
tyrosine. The enzyme tyrosine hydroxylase also uses BH4 as a
cofactor and converts tyrosine to dihydroxyphenylalanine (DOPA).
This is the rate-limiting step in the synthesis of catecholamines.
After DOPA is formed, it can be converted to either melanin or
dopamine. The enzyme tyrosinase converts DOPA to melanin, which
is responsible for skin pigmentation. Alternatively, DOPA
decarboxylase converts DOPA to dopamine, and dopamine β-
hydroxylase converts dopamine to norepinephrine. The enzyme
phenylethanolamine-N-methyltransferase converts norepinephrine to
epinephrine. The steps of catecholamine synthesis are shown in
Figure 1. Note that the enzymes phenylalanine hydroxylase and
tyrosine hydroxylase both use BH4 as a cofactor, whereas the other
enzymes use different cofactors.
Serotonin is synthesized from tryptophan, which is another essential
amino acid. The enzyme tryptophan hydroxylase converts tryptophan
to 5‑hydroxytryptophan. This enzyme actually uses BH4, the same
, cofactor that phenylalanine hydroxylase and tyrosine hydroxylase use
to convert phenylalanine to tyrosine and tyrosine to DOPA. This is
obviously an important cofactor! The enzyme 5‑hydroxytryptophan
decarboxylase then converts 5‑hydroxytryptophan to serotonin. Note
that serotonin can be converted into melatonin, a hormone involved in
regulating sleep within the pineal gland. The steps of serotonin and
melatonin synthesis are shown in Figure 2.
IN-TRAINING
How do you feel about medical students using stimulant drugs to help
with their studies? What do you think the recently reported 15% usage
of stimulants in medical school? What are your thoughts on how to
raise awareness about this phenomenon? At the end of this brick,
please take a few minutes to read a first-person essay about a
medical student’s personal experience with using stimulant drugs and
reflect on a few thought questions.
READ MORE arrow_downward
Degradation of Monoamines
All monoamines are degraded by two main enzymes—catechol-O-
methyltransferase (COMT) and monoamine oxidase (MAO). Rather
than memorizing details of the degradative pathways, it is important
to recognize these enzyme names and the degradative products of
each neurotransmitter. The degradative product of dopamine is
homovanillic acid (HVA). The degradative product of both
