Depolarization of the cell

Note: the release of all neurotransmitters is calcium dependent

They work to change the membrane potential of the postsynaptic cell by opening (or closing) ion channels

-Excitatory neurotransmitters

-inhibitory neurotransmitters

-Ca2+

-Na+

Depolarization

-K+

-Cl-

Hyperpolarization

They mediate the fast effects of neurotransmitters.  The channel is closed during the reseting state and opens when the neurotransmitter binds.

ex: nicotinic cholinergic receptor

ex: GABA-A

ex:NMDA

Works like a hormone receptor, mediates slower effects of neurotransmitters. These receptors are present in peripheral tissue and in the brain

ex: adrenergic receptors

ex: dopamine receptors

ex: muscarinic cholinergic receptors

ex:opiate receptors

Neuromuscular junction: sits in basal lamina

Brain: sits in postsynaptic membrane

both act in extracellular space

Acetyl-Coa + choline in the presence of choline acetyltransferase = AcH

A high energy thioester bond is broken to form a lower energy ester bond

2-step rxn

1.The enzyme has a ser residue with an

-OH sidechain; -OH reacts with the substrate and binds the acetyl group = an acetyl enzyme intermediate (enzyme-ser-acetyl group) while the choline is already released

2. Intermediate undergoes a dehydration rxn.

Curare blocks nicotinic receptors in the neuromuscular junction.  This would block AcH binding, thus it has an antagonistic effect. causes flacid paralysis.

Organophosphates inhibit acetylcholinesterase, irreversibly by acting on the ser residue of the active site.

They are often used as pesticides or chem. warfare

Formed from aromatic amino acids by decarboxylation

They carry a positive charge at ph=7

They are used as neurotransmitters, paracrine messengers, and hormones

tyrosine ydroxylase, which works to attach a new -OH group to tyrosine

[image]

1. dopamine

2. norepinephrine

3. epinephrine

BioH4

[image]

A methyl group is attached to the amine group. via conversion of:

SAM-SAH

(universal methyl donor for biochem rxns)

-L tyrosine

-tyrosine hydroxylase (BiO4=cofactor, -OH group added)

-L DOPA

-Dopa decarboxylase (B6=cofactor, remove CO2, amine group added)

-Dopamine

-Cu+, ascorbate (another -OH group added)

-norephinephrine

-SAM-Sah

-epinephrine

[image]

First they are taken up back into the nerve via: high affinity sodium cotransport uptake

This is followed by inactivation.

1. MAO (deamination)

2. COMT (methylation)

MAO and COMT are both involved in the inactivation of norepinephrine.  It can follow two pathways, where MAO acts followed by COMT or COMT and then MAO

1. norepinephrine

MAO- deamination, to perform this FADH2 must be converted to FAD, however, the toxic byproduct produced is H2O2

COMT- acts to methylate 

2. COMT and SAM- methylate

MAO- deamination

Both pathways result in the same product

step 1: tryptophan hydroxylase: BioH4, NADPH converted to NADP+

step 2: Decarboxylase: B6

step 3: acetyl group attached to the nitrogen

step 4: sam: attaches methyl group

[image]

Homovanillic acid: degraded using MAO B

[image]

vanillymandelic acid: MAO and COMT

[image]

5-hydroxyindolacetic acid: MAO A

[image]

antidepressents

Side effect: hypertensive crisis after exposure to foods containing tyramine (cheese, red wine) 

not commonly prescribed

Because Dopamine is rapidly inactivated by MAOB

The production of L-DOPA involves the production of H2O2 which is a toxic byproduct.  It is a good drug because it can cross the blood brain barrier.

Note: L DOPA is often administered with carbidopa which prevents L dopa from being decarboxylated