Catecholamines Flashcards

1
Q

The three endogenous catecholamines

A
  1. Epinephrine
  2. Norepinephrine
  3. Dopamine
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2
Q

How do cells generate tyrosine if the tyrosine supply is low?

A

Make tyrosine from phenylalanine with the enzyme phenylalanine hydroxylase

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3
Q

Step by step process of dopamine synthesis in dopaminergic cells

A
  1. Tyrosine is converted to L-DOPA by the enzyme tyrosine hydroxylase
  2. L-DOPA is converted to dopamine by the enzyme aromatic L-amino acid decarboxylase
  3. Dopamine is transported into vesicles
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4
Q

The rate limiting step to catecholamine synthesis

A

Tyrosine conversion to L-DOPA by the enzyme tyrosine hydroxylase

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5
Q

How is tyrosine hydroxylase kept in check?

A

Feedback inhibition by dopamine and norepinephrine

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6
Q

Step by step process of norepinephrine synthesis in noradrenergic neurons

A
  1. Tyrosine is converted to L-DOPA by the enzyme tyrosine hydroxylase
  2. L-DOPA is converted to dopamine by the enzyme aromatic L-amino acid decarboxylase
  3. Dopamine is transported into vesicles
  4. Dopamine is converted to norepinephrine by the enzyme dopamine- beta- hydroxylase
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7
Q

Step by step process of epinephrine synthesis in adrenergic neurons and chromaffin cells

A
  1. Tyrosine is converted to L-DOPA by the enzyme tyrosine hydroxylase
  2. L-DOPA is converted to dopamine by the enzyme aromatic L-amino acid decarboxylase
  3. Dopamine is transported into vesicles
  4. Dopamine is converted to norepinephrine by the enzyme dopamine- beta- hydroxylase
  5. Norepinephrine is converted to epinephrine by the enzyme pheylethanolamine N-methyltransferase in the cytoplasm of adrenergic cells
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8
Q

How are catecholamines released?

A

Action potential depolarizes the nerve terminal > Voltage-gated Ca++ channels open > Ca++ diffuses into the nerve terminal > Increased neuronal Ca++ = vesicles fuse with the nerve terminal and release the catecholamine into the synaptic cleft

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9
Q

How is norepinephrine release inhibited?

A

By stimulating presynaptic alpha-2 receptor

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10
Q

How can norepinephrine augment its own release?

A

By stimulating presynaptic beta-2 receptors

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11
Q

In what three ways are catecholamines removed from the synaptic cleft?

A
  1. Reuptake into the presynaptic nerve
  2. Diffusion away from the synaptic cleft with metabolism by MAO and COMT
  3. Reuptake by extraneural tissue
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12
Q

What is the primary mechanism that removes catecholamines from the synaptic cleft?

A

Reuptake into the presynaptic neuron

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13
Q

What are the features of reuptake into the presynaptic neuron?

A

Takes place by active transport- energy-consuming and temperature-dependent process

Most recycled and repackaged into vesicles

Some metabolized by MAO in the nerve terminal

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14
Q

What happens after norepinephrine diffuses away from the synaptic cleft?

A

Enters the circulation > metabolized by MAO and COMT > metabolites excreted in the urine

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15
Q

What happens to norepinephrine if it enters a extraneural tissues?

A

MAO and COMT in the extraneural cells metabolize it

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16
Q

What two enzymes metabolize catecholamines?

A

Monoamine oxidase (MAO)
Catechol-O-methyltransferase (COMT)

17
Q

MAO location

A

Outer membrane of mitochondria of neurons and other tissues

18
Q

COMT location

A

In cytosol in endothelial cells, heart, kidneys, liver, smooth muscle, and glial cells

19
Q

Principle sites of metabolism of catecholamines

A

Liver
Kidneys

20
Q

End product of catecholamine metabolism

A

Vanillylmandelic acid (VMA)

21
Q

How is VMA eliminated from the body?

A

Urine

22
Q

What might high levels of VMA in the urine indicate?

A

Pheochromocytoma

23
Q

Major metabolite of dopamine

A

Homovanillic acid (HVA)