Table of Neurotransmitters

Transmitter Molecule Acetylcholine Serotonin 5-Hydroxytryptamine (5-HT) GABA Glutamate Aspartate Glycine Histamine Epinephrine synthesis pathway Norpinephrine synthesis pathway Dopamine synthesis pathway Adenosine ATP Nitric oxide, NO Arginine Histidine Tyrosine Derived From Choline Site of Synthesis CNS, parasympathetic nerves CNS, chromaffin cells of the gut, enteric cells CNS CNS CNS spinal cord hypothalamus adrenal medulla, some CNS cells CNS, sympathetic nerves

Tryptophan
Glutamate

Tyrosine

Tyrosine ATP

CNS CNS, peripheral nerves sympathetic, sensory and enteric nerves CNS, gastrointestinal tract

 Many other neurotransmitters are derived from precursor proteins, the so-called peptide neurotransmitters. As many as 50 different peptides have been shown to exert their effects on neural cell function. Several of these peptide transmitters are derived from the larger protein pre-opiomelanocortin (POMC). Neuropeptides are responsible for mediating sensory and emotional responses including hunger, thirst, sex drive, pleasure and pain.

Acetylcholine

a simple molecule synthesized from choline and acetylCoA through the action of choline acetyltransferase

Catecholamines
The principal catecholamines are norepinephrine, epinephrine and dopamine These compounds are formed from phenylalanine and tyrosine. Tyrosine is produced in the liver from phenylalanine through the action of phenylalanine hydroxylase. The tyrosine is then transported to catecholamine-secreting neurons where a series of reactions convert it to dopamine, to norepinephrine and finally to epinephrine

Tyrosine-Derived Neurotransmitters
The majority of tyrosine that does not get incorporated into proteins is catabolized for energy production. One other significant fate of tyrosine is conversion to the catecholamines. The catecholamine neurotransmitters are dopamine, norepinephrine, and epinephrine

 Norepinephrine is the principal neurotransmitter of sympathetic postganglionic endings Both norepinephrine and the methylated derivative, epinephrine are stored in synaptic knobs of neurons that secrete it, however, epinephrine is not a mediator at postganglionic sympathetic endings.

 Tyrosine is transported into catecholaminesecreting neurons and adrenal medullary cells where catechaolamine synthesis takes place The first step in the process requires tyrosine hydroxylase, which like phenylalanine hydroxylase requires tetrahydrobiopterin (H4B, or written as BH4) as cofactor.

 Once synthesized, dopamine, norepinephrine and epinephrine are packaged in granulated vesicles. Within these vesicles, norepinephrine and epinephrine are bound to ATP and a protein called chromogranin A.

Tryptophan-Derived Neurotransmitters
Tryptopan serves as the precursor for the synthesis of serotonin (5-hydroxytryptamine, 5-HT, and melatonin (N-acetyl-5methoxytryptamine).

Tryptophan-Derived Neurotransmitters

Pathway for serotonin and melatonin synthesis from tryptophan. Abbreviations: THP = tryptophan hydroxylase, DHPR = dihydropteridine reductase, H2B = dihydrobiopterin, H4B = tetrahyrobiopterin, 5-HT = 5-hydroxytryptophan, AADC = aromatic L-amino acid decarboxylase, SNA = serotonin N-acetylase, HOMT = hydroxyindole-O-methyltransferase.

 Serotonin is synthesized through 2-step process involving a tetrahydrobiopterindependent hydroxylation reaction (catalyzed by tryptophan-5-monooxygenase, also called tryptophan hydroxylase) and then a decarboxylation catalyzed by aromatic Lamino acid decarboxylase. The hydroxylase is normally not saturated and as a result, an increased uptake of tryptophan in the diet will lead to increased brain serotonin content.

 Serotonin is present at highest concentrations in platelets and in the gastrointestinal tract. Lesser amounts are found in the brain and the retina. Serotonin containing neurons have their cell bodies in the midline raphe nuclei of the brain stem and project to portions of the hypothalamus, the limbic system, the neocortex and the spinal cord.

 After release from serotonergic neurons, most of the released serotonin is recaptured by an active reuptake mechanism. The function of the antidepressant, Prozac, and related drugs called selective serotonin re-uptake inhibitors (SSRIs), is to inhibit this reuptake process, thereby, resulting in prolonged serotonin presence in the synaptic cleft.

 The function of serotonin is exerted upon its interaction with specific receptors. Several serotonin receptors have been cloned and are identified as 5HT1, 5HT2, 5HT3, 5HT4, 5HT5, 5HT6, and 5HT7. Within the 5HT1 group there are subtypes 5HT1A, 5HT1B, 5HT1D, 5HT1E, and 5HT1F. There are three 5HT2 subtypes, 5HT2A, 5HT2B, and 5HT2C as well as two 5HT5 subtypes, 5HT5a and 5HT5B. Most of these receptors are coupled to Gproteins that affect the activities of either adenylate cyclase or phospholipase C (PLC). The 5HT3 class of receptors are ion channels.

 Some serotonin receptors are presynaptic and others postsynaptic. The 5HT2A receptors mediate platelet aggregation and smooth muscle contraction. The 5HT2C receptors are suspected in control of food intake as mice lacking this gene become obese from increased food intake and are also subject to fatal seizures. The 5HT3 receptors are present in the gastrointestinal tract and are related to vomiting. Also present in the gastrointestinal tract are 5HT4 receptors where they function in secretion and peristalsis. The 5HT6 and 5HT7 receptors are distributed throughout the limbic system of the brain and the 5HT6 receptors have high affinity for antidepressant drugs.

Melatonin
Melatonin is derived from serotonin within the pineal gland and the retina, where the necessary N-acetyltransferase enzyme is found. The pineal parenchymal cells secrete melatonin into the blood and cerebrospinal fluid. Synthesis and secretion of melatonin increases during the dark period of the day and is maintained at a low level during daylight hours.

 Several amino acids have distinct excitatory or inhibitory effects upon the nervous system. The amino acid derivative, -aminobutyrate, also called 4-aminobutyrate, (GABA) is a wellknown inhibitor of presynaptic transmission in the CNS, and also in the retina. Neurons that secrete GABA are termed GABAergic.

 The formation of GABA occurs by the decarboxylation of glutamate catalyzed by glutamate decarboxylase (GAD). GAD is present in many nerve endings of the brain as well as in the -cells of the pancreas. The activity of GAD requires pyridoxal phosphate (PLP) as a cofactor