LC 3 - neurotransmitters Flashcards
1
Q
catecholamines
A
- Catecholamines are a group of neurotransmitters and hormones that include dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline).
- They play essential roles in the nervous system, particularly in regulating mood, arousal, stress responses, and a variety of other physiological functions.
- The synthesis of catecholamines occurs through a series of enzymatic reactions, primarily in the adrenal medulla and various regions of the brain.
2
Q
synthesis catecholamines
A
- Tyrosine: The precursor for catecholamine synthesis is the amino acid tyrosine, which is obtained from dietary proteins. Tyrosine is transported into the cells where catecholamines are synthesized, such as neurons or chromaffin cells in the adrenal medulla.
- Conversion to L-DOPA: In a reaction catalyzed by the enzyme tyrosine hydroxylase, tyrosine is converted into L-DOPA. This step is considered the rate-limiting step in catecholamine synthesis. Tyrosine hydroxylase requires oxygen and tetrahydrobiopterin (a cofactor) for its activity.
- Conversion to Dopamine: L-DOPA is then decarboxylated to form dopamine, a key neurotransmitter, by the enzyme aromatic L-amino acid decarboxylase (AADC).
- Conversion to Norepinephrine: In neurons that produce norepinephrine, dopamine is further converted to norepinephrine (noradrenaline) by the enzyme dopamine β-hydroxylase. This step occurs in synaptic vesicles, where norepinephrine is stored for release as a neurotransmitter.
- Conversion to Epinephrine: In certain tissues, such as the adrenal medulla, norepinephrine is methylated to form epinephrine (adrenaline) by the enzyme phenylethanolamine-N-methyltransferase (PNMT).
- Storage and Release: Catecholamines, whether dopamine, norepinephrine, or epinephrine, are stored in synaptic vesicles in nerve endings and chromaffin cells. They are released in response to nerve impulses or hormonal signals.
- Reuptake and Inactivation: After release, catecholamines can bind to postsynaptic receptors to exert their effects. They are also subject to reuptake by transporters (e.g., the norepinephrine transporter and dopamine transporter) on the presynaptic neuron. Additionally, enzymes like monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are involved in the breakdown and inactivation of catecholamines.
3
Q
dopaminergic circuit
A
- Dopamine: The substantia nigra and the VTA, both located in the midbrain, are essential for the synthesis of dopamine, a key catecholamine involved in various brain functions, including reward, motivation, and motor control. Dopaminergic neurons in these regions project to other parts of the brain, including the striatum and prefrontal cortex.
4
Q
noradrenergic circuit
A
- Locus Coeruleus:
* Norepinephrine: The locus coeruleus is a nucleus located in the pons of the brainstem. It is the primary source of norepinephrine in the brain. Norepinephrine has widespread projections throughout the brain and plays a significant role in the regulation of arousal, attention, and stress responses. - Adrenal Medulla:
* Epinephrine and Norepinephrine: The adrenal medulla, which is part of the adrenal glands located on top of the kidneys, is responsible for the synthesis and secretion of both epinephrine and norepinephrine into the bloodstream. These hormones are released in response to stress and contribute to the “fight or flight” response.
5
Q
serotonin synthesis
A
- The synthesis of serotonin (5-hydroxytryptamine or 5-HT) involves several steps and primarily occurs in the central nervous system (CNS) and, to some extent, in peripheral tissues.
1. Tryptophan Uptake: Serotonin synthesis begins with the uptake of tryptophan, an essential amino acid, from the bloodstream into neurons. Tryptophan is obtained from dietary sources and competes with other amino acids for transport into cells.
2. Conversion of Tryptophan: Inside the neuron, tryptophan is converted into 5-hydroxytryptophan (5-HTP) through the action of the enzyme tryptophan hydroxylase. This is the rate-limiting step in serotonin synthesis. Tryptophan hydroxylase requires oxygen and the cofactor tetrahydrobiopterin.
3. Conversion of 5-HTP to Serotonin: The enzyme aromatic L-amino acid decarboxylase (AADC) then converts 5-HTP to serotonin (5-HT). AADC removes a carboxyl group from 5-HTP, resulting in the formation of serotonin.
4. Storage and Release: Serotonin is stored in vesicles within the serotonergic neurons, particularly in the raphe nuclei of the brainstem. When an action potential triggers the release of neurotransmitters, serotonin is released into the synaptic cleft, where it can bind to receptors on the postsynaptic neuron.
6
Q
serotonergic circuit
A
- Raphe Nuclei: The raphe nuclei are clusters of serotonergic neurons located in the brainstem, primarily in the midline region of the brainstem. These nuclei are a major source of serotonin production in the CNS. Serotonergic projections from the raphe nuclei extend throughout the brain and spinal cord, playing a critical role in regulating various physiological and behavioural functions.
- Peripheral Tissues: While the majority of serotonin is produced in the CNS, some serotonin is also synthesized in peripheral tissues, especially in the enterochromaffin cells of the gastrointestinal tract. In the gut, serotonin has a role in regulating gut motility and secretion, among other functions. It’s also found in platelets, where it plays a role in blood clotting.
7
Q
glutamate synthesis/circuit
A
- Synthesis: Glutamate is synthesized from another amino acid, glutamine, in a two-step process.
1. Glutamine is converted to glutamate by the enzyme glutaminase. This reaction occurs mainly in astrocytes, a type of glial cell that supports and interacts with neurons.
- After synthesis in astrocytes, glutamate is transported to neurons, where it can be packaged into synaptic vesicles or used in various metabolic processes.
- Location of Production:
- Astrocytes, as mentioned, are a significant source of glutamate production.
- Neurons also produce glutamate locally for immediate neurotransmission.
8
Q
GABA synthesis and production
A
- Synthesis: GABA is synthesized from the excitatory neurotransmitter glutamate through a decarboxylation reaction. The enzyme glutamic acid decarboxylase (GAD) is responsible for converting glutamate into GABA.
- GAD requires the cofactor pyridoxal phosphate (a derivative of vitamin B6) for its activity.
- Location of Production: GABA is primarily synthesized and stored in neurons, specifically in inhibitory interneurons.
9
Q
Acetylcholine synthesis
A
- Synthesis: Acetylcholine is synthesized from two primary components: choline and acetyl-CoA, through a series of enzymatic reactions.
1. Choline Uptake: Choline is obtained from the diet or recycled from degraded cell membranes. It is transported into cholinergic neurons by a specific choline transporter.
2. Acetyl-CoA Formation: Acetyl-CoA is a molecule derived from the metabolism of carbohydrates and fats. It is a key component of the citric acid cycle (Krebs cycle). Acetyl-CoA in neurons is produced in mitochondria.
3. Choline Acetyltransferase (ChAT): The enzyme ChAT catalyzes the reaction that combines choline and acetyl-CoA to produce acetylcholine. This reaction occurs in the cytoplasm of cholinergic neurons.
10
Q
Acetylcholine citcuit
A
- Cholinergic Neurons: Cholinergic neurons are specialized neurons that synthesize, store, and release acetylcholine. They are found throughout the central and peripheral nervous systems.
- Central Nervous System (CNS): Cholinergic neurons in the CNS are primarily located in specific nuclei within the brain, such as the basal forebrain (nucleus basalis of Meynert), the striatum, and the brainstem. These neurons project to various regions of the brain and are involved in functions like memory, attention, and sleep regulation.
- Peripheral Nervous System (PNS): Cholinergic neurons in the PNS play a crucial role in transmitting signals at the neuromuscular junction (for muscle contraction) and within the autonomic nervous system. Parasympathetic preganglionic neurons, postganglionic neurons, and skeletal muscle motor neurons are examples of peripheral cholinergic neurons.
11
Q
Glutamate receptors
A
Glutamate:
* Receptor Type: Mainly ionotropic, which includes NMDA (N-methyl-D-aspartate) receptors and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors. There are also metabotropic glutamate receptors (mGluRs).
* Effect: Ionotropic glutamate receptors are excitatory and stimulate postsynaptic neurons. NMDA receptors have a critical role in synaptic plasticity. AMPA receptors mediate fast excitatory neurotransmission. Metabotropic glutamate receptors can have both excitatory and inhibitory effects, depending on the specific subtype and downstream signaling pathways.
12
Q
GABA receptors
A
- Receptor Type: Mainly ionotropic, including GABA_A (gamma-aminobutyric acid type A) receptors and GABA_C receptors. There are also metabotropic GABA receptors, such as GABA_B receptors.
- Effect: Ionotropic GABA receptors are inhibitory and hyperpolarize postsynaptic neurons. GABA_A receptors are involved in fast inhibitory synaptic transmission. GABA_C receptors are also inhibitory but less common. Metabotropic GABA_B receptors are typically inhibitory.
13
Q
Acetylcholine receptors
A
- Receptor Type: Muscarinic acetylcholine receptors are metabotropic. Nicotinic acetylcholine receptors are ionotropic.
- Effect: Muscarinic receptors, such as M1, M2, M3, etc., can be both excitatory and inhibitory, depending on the subtype and the downstream signaling pathways. Nicotinic receptors, including neuronal nAChRs and muscle-type nAChRs, are typically excitatory and stimulate postsynaptic neurons, often leading to muscle contraction.
14
Q
serotonin receptors
A
- Receptor Type: Serotonin receptors are primarily metabotropic, divided into multiple subtypes, such as 5-HT1, 5-HT2, etc.
- Effect: The effects of serotonin receptors can be complex and depend on the specific subtype and location. They can be excitatory or inhibitory, depending on the receptor subtype and the downstream signaling pathways.
15
Q
dopamine receptors
A
- Receptor Types: Dopamine acts on several receptor types, including D1-like receptors (D1 and D5), which are metabotropic receptors, and D2-like receptors (D2, D3, and D4), which are also metabotropic receptors.
- Effect: The effects of dopamine receptors can be complex. D1-like receptors are generally excitatory and stimulate postsynaptic neurons, while D2-like receptors are inhibitory and can inhibit postsynaptic neurons. Both receptor types are metabotropic.
