Chemistry Of Neurotransmitters Flashcards
What are the 4 criteria of a NT?
1) synthesized and stored in the presynaptic neuron (not actually true)
2) released in response to an AP
3) specific post-synaptic receptors
4) mechanism for removal
What is neurotransmitter modulation?
Changing excitability without directly causing an EPSP or an IPSP
What are the stages in the life cycle of a NT?
1) synthesis
2) storage
3) degradation possibly
4) release
5) inhibitory feedback by autoreceptors
6) activation of post receptors
7) deactivation
What are the two broad categories of NTs?
Small molecule transmitters and neuropeptides
What are the chain lengths of small molecule NTs vs neuropeptides?
Small molecule NTs: about 1 amino acid
Neuropeptides: 3-36 amino acids
Which broad category of NT mediates fast, synaptic actions?
Small molecule NTs
Which broad category of NTs mediates slower, ongoing synaptic functions?
Neuropeptides
Where are small molecule transmitters synthesized?
Cytoplasm
Where are neuropeptides synthesized?
Inside vesicles
What four amino acids are considered NTs? What are their cell effects?
GABA, glycine = inhibitory glutamate, aspartate = excitatory
What is the main inhibitory NT in the Brain?
GABA
What is the main inhibitory NT in the spinal cord?
Glycine
Glutamate and aspartate receptors conduct which ions?
Sodium
To which broad category of NT does glutamate belong?
Small molecule NTs
Glutamine becomes glutamate through which enzyme?
Glutaminase
Nearly all excitatory neurons in the brain release what NT?
Glutamate
Why must glutamate be synthesized in neurons?
It can’t cross the BBB
Explain small molecule NT synthesis in glutamatergic neurons
Synthesis of glutaminase in the soma, then slow transport of these enzymes down the axon, then NT synthesis and packaging into terminal
Describe the process of turning glutamate back to glutamine
Glutamate from the synaptic cleft is transported into a glial cell by the glutamate transporter and within that glial cell the glutamine synthase enzyme converts it to glutamine which is then pumped out of the glia cell by the glutamine transporter and then transported back to the terminal
GABA is synthesized in neurons from what precursor molecule?
Glutamate
What enzyme converts glutamate into GABA?
GAD, glutamic acid decarboxylase
GABA and glycine channels conduct what ion?
Chloride
What types of receptors can bind benzodiazepines?
GABA
Explain small molecule NT synthesis in GABAergic neurons
Glutamate already present in presynaptic terminal, GAD synthesized in soma and transported by microtubules down the axon, glutamate converted to GABA by GAD
Explain the process of GABA recycling
GABA from the synaptic cleft is taken back into the presynaptic cell by the GABA transporter. GABA is then packaged into vesicles by the GABA vesicular transporter.
What are the 5 sites on the GABA receptor?
Picrotoxin, barbiturate, GABA, steroid, benzodiazepine
What is the effect of alcohol and anti-anxiety medications on GABA receptors?
It stimulates them
Epileptic seizures are a result of having a deficiency of which NT?
GABA
Why are diffuse modulatory systems targets of drugs?
They modulate brain states like mood, arousal, and sleep
Why is acetylcholine considered separately as a NT?
It is neither an amino acid or modified from one
Where is ACH excitatory?
Neuromuscular junctions and autonomic nervous system synapses
ACH receptors also bind what?
Nicotine
Where are ACH neurons found in the brain?
Brainstem and basal forebrain
What is the brain ACH system involved in?
Sleep, attention, and memory
Defects in ACH transmission are seen in what diseases?
Alzheimer’s and Parkinson’s
What enzyme converts Acetyl CoA and choline into ACH?
CHAT
What enzyme degrades ACH?
ACHE, acetylcholinesterase
What often targets the AchE enzyme?
Drugs used to treat neuromuscular diseases like Alzheimer’s & some animal venoms, insecticides and chemical weapons
What is the effect of a-bungarotoxin on ACH receptors?
Blocks them irreversibly
What are the 5 biogenic amines?
Serotonin, dopamine, norepinephrine, histamine, epinephrine
What are the monoamines?
Dopamine, norepinephrine, epinephrine, and serotonin
Which NTs are catecholamines?
Norepinephrine, epinephrine, and dopamine
What two features must a NT have to be considered a catecholamine?
A catechol group and an amino group
The dopamine catecholamine pathway in the brain involves what regions?
Neurons found in substantia nigra and VTA
Norepinephrine catecholamine pathway in the brain involves mainly what region?
Locus coeruleus
Epinephrine catecholamine pathway in the brain involves what region?
Medullary epinephrine neurons
What is the enzyme that converts tyrosine to L-DOPA?
TH, tyrosine hydroxylase
What enzyme converts dopamine to norepinephrine?
DBH, Dopamine B-Hydroxylase
What enzyme converts norepinephrine to epinephrine?
PNM
What is the precursor of all catecholamines?
Tyrosine
What enzyme converts L-DOPA to dopamine?
AAAD
What cofactors are needed for the conversion of L-tyrosine to L DOPA?
Iron 2, BH4, O2
Dopamine, EPI, NOR, histamine, and serotonin are transported into vesicles by what?
VMAT; non-selective for amines
What cofactors are needed to convert dopamine into norepinephrine?
Ascorbic acid & O2
Which catecholamine is synthesized in vesicles?
Norepinephrine
TH is unique to what types of neurons?
Catecholamine-containing neurons
What is the rate limiting step of catecholamine synthesis, and what cofactor is the most important?
TH is RLS, BH4 most important
Where is the ubiquitous enzyme AAAD found?
In the cytoplasm
Where is DBH located and why?
Inside vesicles, synthesis of NOR happens here
Where is PNMT located and why?
In the cytoplasm, epinephrine is made outside the vesicle and then brought in later
What are the roles of dopamine?
Coordination of movement, motivation, reward, reinforcement
What are the 3 methods of removal of dopamine from the synaptic cleft?
1) DAT, dopamine active transporter
2) MAO enzyme
3) COMT enzyme
MAO inhibitors treat what diseases?
Depression & Parkinson’s
COMT enzyme inhibitors treat what disease?
Parkinson’s
What are the roles of norepinephrine?
Sleep, wakefulness, arousal, attention, and feeding
What enzymes are involved in the degradation and removal of norepinephrine?
1) NET, norepinephrine transporter
2) MAO
2) COMT
What is the role of epinephrine?
Acts on cardiovascular tissues, fight or flight
What enzymes are involved in the degradation of epinephrine?
1) NET
2) MAO
3) COMT
What are the roles of serotonin?
Sleep, wakefulness, depression, anxiety
What is the precursor for serotonin?
Tryptophan
What enzyme converts tryptophan to serotonin?
Tryptophan 5 hydroxylase
What are the methods of reuptake/degradation of serotonin?
Reuptake by serotonin transporter (SERT), degradation by MAO
How does Prozac treat depression?
Prevents serotonin reuptake by blocking the SERT transporter
Many neuropeptides are also what?
Hormones
Neuropeptides have general roles in what?
Emotion, pain, stress, homeostasis
True or false: neuropeptides and small molecule neurotransmitters are colocalized together
True
What are the 3 endogenous opioid peptides?
Endorphins, enkephalins, dynorphins
To which general class of neurotransmitters do opioids belong?
Neuropeptides
What are opioids co-localized with?
GABA, serotonin
What are the effects of opioids on the human body?
Control of pain and tend to be depressants
What are the steps of synthesis of peptide NTs (how opioids would be synthesized)?
1) pre-propeptides synthesized in rough ER
2) packaged into transport vesicles in the golgi
3) broken down into neuropeptides by enzymes in synaptic vesicles
Run through the steps of neuropeptides transport and storage
1) synthesis and packaging of propeptides in soma
2) fast transport of vesicles containing the propeptides down the axon
3) final neuropeptide synthesis in the terminal
What type of NTs have no mechanism for reuptake?
Neuropeptides, inactivated by peptidases which cleave them into amino acids
What types of NTs have both ionotropic and metabotropic receptors?
Amino acid transmitters, ACH, and serotonin; all the rest are metabotropic
Are autoreceptors ionotropic or metabotropic?
Metabotropic
What are the two most common mechanisms utilized by autoreceptors?
1) inactivation of calcium channels
2) inhibition of synthetic enzymes such as TH
