Transcript 4 Neurotransmitters GOB Structures

18.4 Neurotransmitters
A neurotransmitter
is a chemical
compound that
transmits an impulse
from a nerve cell to a
target cell. Target
cells may be another
nerve cell, a muscle
cell, or a gland cell.
Learning Goal Describe the role
of amines as neurotransmitters.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
A nerve cell consists of a cell body and filaments
called axons and dendrites that form junctions
with nearby nerve cells to transmit nerve
impulses.
© 2016 Pearson Education, Inc.
Neurons
A neuron, also known as a nerve cell, consists of
• a cell body and numerous filaments called
dendrites at one end.
• an axon that ends at the axon terminal at the
opposite end.
• junctions called synapses formed between the
axon terminals and dendrites of other nerve cells.
Within a nerve cell, neurotransmitters are
synthesized and stored in vesicles at the end of the
axon terminal.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Neurotransmitters at the Synapse
When an electrical signal reaches the axon terminal of a nerve cell,
• neurotransmitters are released into the synapse and taken up by
the dendrites in nearby nerve cells.
• electrical impulses and chemical transmitters move information
through a network of nerve cells in a very short period of time.
Neurotransmitters can be
• excitatory, stimulating the receptors to send more impulses.
• inhibitory, decreasing the activity of the receptors.
The binding of an excitatory neurotransmitter opens ion channels in
nearby nerve cells, releasing more neurotransmitters.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Termination of Neurotransmitters
Neurotransmitters can be removed from the
receptors in different ways:
1. The neurotransmitter diffuses away from the
synapse.
2. Enzymes in the receptors break down the
neurotransmitter.
3. Reuptake returns the neurotransmitter to the
vesicles, where it is stored.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Amine Neurotransmitters
Neurotransmitters contain nitrogen atoms as amines and
alkylammonium ions;
• they are synthesized from compounds such as amino
acids obtained from our diets.
• their amino groups are usually ionized, forming
ammonium cations and carboxylate anions.
Important amine neurotransmitters include acetylcholine,
dopamine, norepinephrine (noradrenaline), epinephrine
(adrenaline), serotonin, histamine, glutamate, and GABA.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Acetylcholine
Acetylcholine
• communicates between the nervous system and
the muscle.
• regulates muscle activation as well as learning and
short-term memory.
• is synthesized by forming an ester between choline
and acetate and is stored in the vesicles.
• is released into the synapse, where it binds to
receptors on the muscle cells and causes the
muscles to contract.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Acetylcholine
• To enable continual nerve transmission, acetylcholine
is quickly degraded by enzymes that hydrolyze the
ester bond.
• The loss of the acetylcholine at the receptors causes
muscle cells to relax.
• The resulting choline and acetate are converted back
to acetylcholine and stored in the vesicles.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Acetylcholine Loss in Adults
In older adults, a decrease in acetylcholine
• produces gaps in short-term memory.
• by 90% causes severe loss of reasoning and motor
function and is known as Alzheimer’s disease.
Medications that are cholinesterase inhibitors, such as
Aricept, are used to slow the breakdown of acetylcholine
in order to maintain the acetylcholine levels in the brain.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Nerve Poisons
Nerve poisons such as Sarin, Soman, and Parathion
• bind to the acetylcholinesterase enzyme and inhibit
its action.
• result in a buildup of acetylcholine in the synapse,
stopping nerve transmissions.
Because acetylcholine cannot be released, the
muscles in the body cannot relax, and convulsions
and respiratory failure soon occur.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Catecholamines
The most important catecholamine neurotransmitters are
• dopamine, norepinephrine, and epinephrine.
• closely related in structure.
• synthesized from the amino acid tyrosine found in
meats, nuts, eggs, and cheese.
Amphetamine and methamphetamine are synthetic
central nervous system stimulants that increase excitatory
catecholamine neurotransmitters, particularly dopamine
and norepinephrine.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Amphetamines
Amphetamine and methamphetamine
• are synthetic central nervous
system stimulants.
• increase excitatory catecholamine
neurotransmitters, particularly
dopamine and norepinephrine.
Amphetamine is used in the treatment
of ADHD to improve cognition and
decrease hyperactivity.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Catecholamines
The neurotransmitters
dopamine, norepinephrine,
and epinephrine are
synthesized from the amino
acid tyrosine after it is
converted to L-dopa.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Dopamine
Dopamine, produced in the nerve cells of the midbrain,
• works as a natural stimulant to give us energy and
feelings of enjoyment.
• plays a role in controlling muscle movement and
regulation of the sleep–wake cycle and helps to
improve cognition, attention, memory, and learning.
Reuptake may be blocked by cocaine and
amphetamines, leaving dopamine in the synapse.
High levels of dopamine may contribute to addictive
behavior and schizophrenia.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
L-Dopa
Increases Dopamine
L-Dopa
is used to
increase dopamine
levels in the brain.
Parkinson’s
disease causes the
midbrain nerve
cells to lose their
ability to produce
dopamine.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Norepinephrine and Epinephrine
Norepinephrine (noradrenaline) and epinephrine
(adrenaline)
• are hormonal neurotransmitters.
• play a role in sleep, attention and focus, and alertness.
• are normally produced in the adrenal glands and are
produced in large quantities when the stress of physical
threat is causing the flight-or-fight response.
Epinephrine is synthesized from norepinephrine by the
addition of a methyl group to the amine.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Serotonin
Serotonin (5-hydroxytryptamine)
• helps us to relax, sleep deeply and peacefully, and
think rationally and gives us a feeling of well-being
and calmness.
• is synthesized from the amino acid tryptophan, which
can cross the blood-brain barrier.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Serotonin and Depression
Low levels of serotonin in the brain may be
associated with depression, anxiety disorders,
obsessive-compulsive disorder, and eating disorders.
Many antidepressant drugs, such as fluoxetine
(Prozac) and paroxetine (Paxil), are selective
serotonin reuptake inhibitors, SSRIs.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Serotonin and Depression
When the reuptake of serotonin is slowed by SSRIs,
it remains longer at the receptors, where it continues
its action; the net effect is as if additional quantities of
serotonin were taken.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Histamine
Histamine is
• synthesized in nerve cells in the hypothalamus
from the amino acid histidine.
• produced by the immune system in response to
pathogens and invaders or injury.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Histamine, Antihistamines
Histamine
• combines with histamine receptors to cause
allergic reactions, which may include inflammation,
watery eyes, itchy skin, and hay fever.
• is also stored and released in the cells of the
stomach, where it stimulates acid production.
Antihistamines, such as Benadryl, Zantac, and
Tagamet, are used to block the histamine receptors
and stop the allergic reactions.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Glutamate
Glutamate
• is the most abundant neurotransmitter in the
nervous system.
• is used to stimulate over 90% of the synapses.
When glutamate binds to its receptor cells, it
stimulates the synthesis of nitrogen oxide (NO), also
a neurotransmitter in the brain.
Glutamate and NO are thought to be involved in
learning and memory.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Glutamate Levels
In Lou Gehrig’s disease (ALS), production of an
excessive amount of glutamate causes the
degeneration of nerve cells in the spinal cord.
As a result, a person with Lou Gehrig’s disease
suffers increasing weakness and muscular atrophy.
When the reuptake of glutamate is too rapid, the
levels of glutamate fall too low in the synapse, which
may result in mental illness such as schizophrenia.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
GABA
Gamma(γ)-aminobutyric acid, or GABA,
• is produced from glutamate and is the most common
inhibitory neurotransmitter in the brain.
• reduces anxiety by inhibiting the ability of nerve cells to send
electrical signals to nearby nerve cells.
• is involved in the regulation of muscle tone, sleep, and
anxiety.
GABA can be obtained as a nutritional supplement.
Medications such as benzodiazepines and barbiturates such as
phenobarbital are used to increase GABA levels at the GABA
receptors.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
GABA from Glutamate
Alcohol, sedatives, and tranquilizers increase the
inhibitory effects of GABA. Caffeine decreases the
GABA levels in the synapses, leading to conditions of
anxiety and sleep problems.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Summary of Neurotransmitters
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.