BIOGENIC AMINES DR AMINA TARIQ BIOCHEMISTRY CATECHOLAMINES Dopamine

BIOGENIC AMINES 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.

� Dopamine + CO 2 �Enzyme – Dopa decarboxylase �Coenzyme – pyridoxal PO 4

�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: 1. Monoamine oxidases 2. Catechol-O-methyl transferases.

� 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: 1. Low Energy, 2. Decreased Focus ability and 3. Sleep cycle problems.

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