Biochemistry of

neurotransmitters
What is a neurotransmitter?
A chemical substance that:
Is synthesized and stored in a presynaptic neuron (the
enzymes needed for its synthesis must be present in the
neuron),
Is released at a synapse following depolarization of the
nerve terminal (usually dependent on influx of calcium
ions),
binds to receptors on the postsynaptic cell and/or
presynaptic terminal,
elicits rapid-onset and rapidly reversible responses in
the target cell,
Is removed or inactivated from the synaptic cleft.
They are chemicals that communicate information
throughout our brain and body.

They can also affect mood, sleep, concentration,

weight, and can cause adverse symptoms when they
are out of balance.
The neurotransmitters are
stored in tiny sac-like
structures called vesicles at
the end of axons. When an
impulse, or nerve signal,
reaches the end of the axon,
the vesicles release a
neurotransmitter into the
small space between the
adjoining cells (synaptic cleft).

Enzymes concerned with the

synthesis of neurotransmitters are
present both in the cell body and
in the nerve ending.
A portion of neurotransmitter is
produced in the cell body and
transported to the nerve ending.
Neurotransmitters diffuse
across the synapse and
bind to receptors in the
receiving cell that are
specific for the
neurotransmitter. The kinds
of reactions that occur in
the receiving cell may vary.
The cell may be excited and
an action potential is set up
and the impulse is
transmitted; or the opposite
effect may occur, and the
cell will be inhibited from
transmitting the impulse
because it becomes
hyperpolarized.
If neurotransmitters were
allowed to operate over a
long period of time, the
results would be disastrous
for the organism since there
would be a constant
overload of messages being
sent.
One way in which the
problem is solved is
through enzymes which
break down the
neurotransmitter very
rapidly.
Different types of cells secrete different
neurotransmitters.
Each brain chemical works in widely spread but fairly
specific brain locations and may have a different effect
according to where it is activated.
All of the major neurotransmitters are made from
amino acids except acetylcholine. Some 60
neurotransmitters have been identified.
The knowledge about the neurotransmitters has led to
the development of successful products for many brain
disorders including epilepsy, schizophrenia,
Parkinson’s disease, depression, anxiety disorders and
migraine .
Neurotransmitter levels can be depleted many ways.
Stress, poor diet, neurotoxins, genetic predisposition,
drug (prescription and recreational), alcohol and
caffeine usage can cause these levels to be out of
optimal range.
Types of Neurotransmitters
There are two kinds of neurotransmitters –
INHIBITORY and EXCITATORY.
Excitatory neurotransmitters are not necessarily
exciting – they are what stimulate the brain.
Those that calm the brain and help create balance are
called inhibitory. Inhibitory neurotransmitters
balance mood and are easily depleted when the
excitatory neurotransmitters are overactive.
 Types of neurotransmitters
Small-molecule
Amines (acetylcholine, adrenaline, noradrenaline
histamine,dopamine, serotinin, etc.) biogenic amines
(dopamine, noradrenaline, serotonin and histamine) are often referred to
as a ‘discrete group’ because of their similarity in terms of their chemical
properties.
Amino acids (glutamate, aspartate)
Neuropeptides : relatively larger
 Gases (nitric oxide)
 Small molecule neurotransmitters
Type Neurotransmitter Postsynaptic effect

Acetylcholine Excitatory

Amino acids Gamma aminobutyric Inhibitory

acid (GABA)

Glycine Inhibitory
Glutamate Excitatory
Aspartate Excitatory
Biogenic amines Dopamine Inhibitory
Nor adrenaline Excitatory
Serotonin Inhibitory
Histamine Excitatory
ACETYLCHOLINE
Acetylcholine was the first neurotransmitter to be
discovered.
It is responsible for much of the stimulation of
muscles, including the muscles of the gastro-intestinal
system.
It is also found in sensory neurons and in the
autonomic nervous system, and has a part in
scheduling REM (dream) sleep.
Acetylcholine is transmitted within cholinergic pathways that
are concentrated mainly in specific regions of the brainstem
and are thought to be involved in cognitive functions,
especially memory. Severe damage to these pathways is the
probable cause of Alzheimer’s disease.(There is something on
the order of a 90% loss of acetylcholine in the brains of people
suffering from Alzheimer's, which is a major cause of senility )
Outside the brain, acetylcholine is the main
neurotransmitter in the parasympathetic nervous
system – the system that controls functions such as
heart rate, digestion, secretion of saliva and bladder
function.

The plant poisons curare cause paralysis by blocking

the acetylcholine receptor sites of muscle cells.

The well-known poison botulin works by preventing

the vesicles in the axon ending from releasing
acetylcholine, causing paralysis.
SEROTONIN

SEROTONIN is an inhibitory neurotransmitter –

which means that it does not stimulate the brain.
 Adequate amounts of serotonin are necessary for a
stable mood and to balance any excessive excitatory
(stimulating) neurotransmitter firing in the brain.
If you use stimulant medications or caffeine in your
daily regimen – it can cause a depletion of serotonin
over time.
Within the brain, serotonin is localized mainly in
nerve pathways emerging from the raphe nuclei, a
group of nuclei at the centre of the reticular formation
in the Midbrain, pons and medulla.
These serotonergic pathways spread extensively
throughout the brainstem , the cerebral cortex and
the spinal cord .
An imbalance of serotonin in the brain is thought to contribute
to depression, anxiety, poor mood, sexual dysfunction, OCD
and stress
The most common antidepressants are called selective
serotonin reuptake inhibitors (SSRIs). They’re considered
relatively safe and cause fewer side effects than other kinds of
medications used to treat depression
Largest amount of serotonin is found in the intestinal
mucosa.

Although the CNS contains less than 2% of the total

serotonin in the body, serotonin plays a very important
role in a range of brain functions. It is synthesized
from the amino acid tryptophan.
Low serotonin levels leads to an increased appetite for
carbohydrates (starchy foods) and trouble sleeping,
which are also associated with depression and other
emotional disorders. It has also been tied to
migraines, irritable bowel syndrome, and
fibromyalgia.

Low serotonin levels are also associated with

decreased immune system function.
In addition to mood control, serotonin has been
linked with a wide variety of functions, including the
regulation of sleep, pain perception, body
temperature, blood pressure and hormonal activity
Gamma amino butyric acid
(GABA)
Gamma amino butyric acid(GABA) is the major
inhibitory neurotransmitter that is often referred to as
“nature’s VALIUM-like substance”. When GABA is out
of range (high or low excretion values), it is likely that
an excitatory neurotransmitter is firing too often in the
brain. GABA will be sent out to attempt to balance
this stimulating over-firing.
GABA
GABA is present in high concentrations (millimolar)
in many brain regions.
These concentrations are about 1,000 times higher than
concentrations of the classical monoamine
neurotransmitters in the same regions.
GABA is derived from glucose, which is transaminated
in the Kreb’s cycle to glutamine and then converted to
GABA by the enzyme, glutamic acid decarboxylase.
Glucose Glutamine GABA.
People with too little GABA tend to suffer from anxiety
disorders, and drugs like Valium work by enhancing
the effects of GABA. Lots of other drugs influence
GABA receptors, including alcohol and barbiturates.
If GABA is lacking in certain parts of the brain,
epilepsy results.
Tyrosine-Derived
Neurotransmitters
Dopamine, norepinephrine, and epinephrine
Diet/ phenylalanine
liver hydroxylase

Rate-limiting Vitamin B12 or folate

step

Pyridoxal phosphate vesicular

Glutamate and aspartate
Nonessential amino acids
Do not cross BBB
must be synthesized in neurons
Main synthetic compartments
neurons
glial cells
Both are excitatory neurotransmitters.
THANKS