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Transcript
DR AMINA TARIQ
BIOCHEMISTRY
CATECHOLAMINES
 Dopamine
 Norepinephrine
 Epinephrine
These are biogenic amines and are called
catecholamines.
Dopamine and Norepinephrine function as
neurotransmitters in the brain and autonomic nervous
system.
 Norepinephrine and Epinephrine are also synthesized
in the adrenal medulla.
 Synthesized from amino acid tyrosine.
 Dopa (3,4 dihydroxyphenyl alanine)
Enzyme – Tyrosine hydroxylase
Coenzyme – Tetrahydrobiopterin
Abundant in CNS, Adrenal medulla, sympathetic
ganglia.
 Rate limiting step.
 Step occurs in mitochondria.


Dopa
Dopamine + CO2
 Enzyme – Dopa decarboxylase
 Coenzyme – pyridoxal PO4
 Dopamine is also a neurotransmitter.
 Step occurs in the cytoplasm.


Dopamine
Norepinephrine
 Enzyme – Dopamine hydroxylase
 Copper containing enzyme
 Dopamine enters the storage granules of chromaffin
cells.


Norepinephrine
Epinephrine
 Enzyme- N-methyl transferase
 Methyl group donor is S- adenosyl methionine.
 Cytoplasm
Source
 Almost all adrenaline and half of dopamine comes
from adrenal medulla.
 Most of the noradrenaline and the remaining
dopamine diffuse into the blood stream from nerve
endings, released as neurotransmitters.
FATE
 The catecholamines are degraded by enzymes called:
Monoamine oxidases
2. Catechol-O-methyl transferases.
1.

Epinephrine (norepi)
COMT


Metanephrine (normeta)
MAO
Vanillylmandelic acid

Epin/Norepin
MAO
Dihydroxy mandellic acid
COMT

Vanillylmandelic acid
MAO INHIBITORS
 Prevent the degradation of NE, dopamine and
serotonin.
 Their levels in the pre synaptic vesicles increase, they
leak out in the synaptic space.
 And activate their receptors.
 This is responsible for the anti depressant effect of
MAO inhibitors.(Tricyclics and selective serotinin
reuptake inhibitors).
DOPAMINE
 DOPAMINE is our main focus
neurotransmitter. When dopamine is either elevated
or low – we can have focus issues such as not
remembering where we put our keys, forgetting what a
paragraph said when we just finished reading it or
simply daydreaming and not being able to stay on
task.
 Dopamine is also responsible for our drive or desire to
get things done – or motivation.
 Common symptoms with low dopamine levels are loss
of motor control, addictions, cravings, compulsions,
and loss of satisfaction.
 When dopamine levels are elevated symptoms may
manifest in the form of anxiety or hyperactivity.
 Drugs like cocaine, opium, heroin, and alcohol
increase the levels of dopamine, as does nicotine.
 The severe mental illness schizophrenia has been
shown to involve excessive amounts of dopamine in
the frontal lobes, and drugs that block dopamine are
used to help schizophrenics.
 On the other hand, too little dopamine in the motor
areas of the brain are responsible for Parkinson's
disease, which involves uncontrollable muscle
tremors.
 Dopamine is a derivative of the amino acid tyrosine.
Dopamine is produced by neurons located in a part of
the brain called the Substantia Nigra (Black
Substance), which is part of the Basal Ganglia (a group
of structures in the midbrain).
 Dopamine is also a neurohormone released by the
hypothalamus. Its main function as a hormone is to
inhibit the release of Prolactin from the anterior lobe
of the Pituitary.
 Dopamine is a sympathomimetic catecholamine which
exhibits alpha adrenergic, beta adrenergic, and
dopaminergic agonism.
 Dopamine can have either an excitatory or inhibitory
effect on the postsynaptic potential. When dopamine
leaves the presynaptic neuron and goes into the
synapse, it can then bind to receptors on the
postsynaptic neuron.
 After dopamine is bound to the postsynaptic cell, it
can either facilitate an action potential or inhibit it. A
neuron that classically releases dopamine is called a
dopaminergic neuron.
FUNCTIONS
 Dopamine plays a significant role in the
cardiovascular, renal, hormonal, and central nervous
systems.
1. Dopamine is useful in the management of states of
low cardiac output, associated with compromised
renal function as with cardiogenic and hypovolemic
shock.
2. Dopamine also causes the release of norepinephrine
from nerve terminals, which contributes to its effects
on the heart.
3. Dopamine usually increases the systolic and pulse
pressure and either has no effect on the diastolic blood
pressure or increases it slightly.
4. Dopamine produces positive chronotropic and
inotropic effects on the myocardium, resulting in
increased heart rate and cardiac contractility.
NOREPINEPHRINE
 NOREPINEPHRINE is an excitatory neurotransmitter
that is responsible for stimulatory processes in the
body. Norepinephrine helps to make epinephrine as
well. This neurotransmitter can cause ANXIETY at
elevated excretion levels as well as some “MOOD
DAMPENING” effects.
 Low levels of norepinephrine are associated with:
Low Energy,
2. Decreased Focus ability and
3. Sleep cycle problems.
1.
EPINEPHRINE
 EPINEPHRINE is an excitatory neurotransmitter that
is reflective of stress.
1. This neurotransmitter will often be elevated when
ADHD like symptoms are present.
2. Long term STRESS or INSOMNIA can cause
epinephrine levels to be depleted.
3. Epinephrine also regulates HEART RATE and
BLOOD PRESSURE.
 Low levels of epinephrine contribute to fatigue, weight
gain and poor concentration.
 Elevated levels of epinephrine can be factors
contributing to restlessness, anxiety, sleep problems,
or acute stress.
FUNCTIONS
 Regulators of carbohydrate and lipid metabolism.
 Increase the degradation of glycogen and TG.
 Increase blood pressure and output of heart.
Learning Resources
 Lecture Notes
 Lippincott biochemistry