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Serotonin (also called 5-HT because of its chemical name, 5-hydroxytryptamine) is a neurotransmitter that is produced naturally in our body. As a neurotransmitter, serotonin carries signals along and between nerve cells (neurons). It’s found mainly in the intestines but also in the central nervous system (CNS) and the blood platelets.
Serotonin is synthesised in serotonergic terminals from the amino acid tryptophan, which competes with tyrosine and the branched chain amino acids for transport across the blood-brain barrier. Tryptophan is converted to 5-Hydroxytryptophan (5-HTP) through the process of hydroxylation facilitated by the enzyme tryptophan hydroxylase (Tph-1). 5-HTP is the intermediate metabolite of the essential amino acid tryptophan in the biosynthesis of serotonin and with the help of the enzyme aromatic amino acid decarboxylase (AAAD) undergoes decarboxylation in which is converted into serotonin, or in other words 5-hydroxytryptamine (5-HTP).
Figure 1. Biosynthesis of Serotonin from Tryptophan
Serotonin has an important role in a number of bodily functions. It is vital for positive mood, good appetite and sleep, digestion, sexual function, blood clotting and bone density. As we get older serotonin levels start declining. Food cravings for simple carbs and salty foods often stem from low serotonin levels. These foods may offer a quick fix, but it is one that does not last. Thus a vicious cycle of more food cravings occur which could potentially become risk factor for the development of many illnesses.
When serotonin levels are optimal we experience a great mood during the day and a restful sleep at night. When serotonin levels are low so is our self-confidence. This is because serotonin keeps the right and left hemisphere of the brain in balance. When this balance is compromised it would result with disconnection between the brain's left side's rationality and right side's creativity and as a consequence lead to low mood, depression and trouble falling asleep. Serotonin also plays an important role in the production of melatonin (the sleep hormone). Within the pineal gland, serotonin is acetylated and then methylated to produce melatonin which is an important regulator for normal sleep patterns.
Figure 2. Biosynthesis of Melatonin from Serotonin
In the brain, serotonin acts as a neurotransmitter or chemical message which is being sent across the gap called the synapse between nerve cells. The cell sending the message, called the pre-synaptic cell, releases serotonin into the synapse. The serotonin is taken in by the receiving, post-synaptic cell, or be taken back by the pre-synaptic cell. In depression the post-synaptic cell doesn't take in enough serotonin and the message gets lost. The most commonly used drugs against depression are serotonin selective re-uptake inhibitors (SSRIs) which decrease the ability of the pre-synaptic cell to reuptake the serotonin, leaving the message in the synapse longer and giving the post-synaptic cell a better chance of receiving the serotonin.
The predominant site of serotonin synthesis, storage, and release is the enterochromaffin (EC) cells of the intestinal mucosa. Within the intestinal mucosa, serotonin released from EC cells activates neural reflexes associated with intestinal secretion, motility and sensation. On this way it stimulates the production and release of gastric and colonic mucus important for normal digestion. Dysregulation of serotonin would lead to diarrhoea or constipation. Moreover, conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) have been associated with low serotonin levels (Costedio et al., 2007). This is because serotonin can act as a pro-inflammatory molecule and can modulate immune cell function in the gut.
Serotonin is also involved in food intake control, with serotonin high levels reducing total energy intake or selectively reducing carbohydrate selection over protein. Serotonin exhibits control over hunger through several receptors with different functions. There are seven different families of 5-HT receptors, and in some of these families there are many receptor subtypes, mainly 5-HT1 and 5-HT2 receptors. These receptors are responsible for the reduced food intake associated with serotonin. Recent studies have also demonstrated an ability of serotonin to activate neurons and receptors such as melanocortin-4 receptors ( MC4Rs) which curb appetite, and at the same time block other neurons that normally act to increase appetite (Sharma & Sharma, 2012).
Serotonin contributes to the formation of blood clots. It is released by platelets (disc shaped red blood cells) when there is a wound. The resulting vasoconstriction, or narrowing of the blood vessels, reduces blood flow and helps blood clots to form. When activated, the platelets release the contents of small packages that they carry called delta granules. These packages contain calcium, various energy-containing molecules, and serotonin. When the delta granules are released by activated platelets, the serotonin and other molecules work in the injured area to amplify the coagulation response.
The serotonin derived from the GI tract and transported through the circulation is the major source for skeletal serotonin. Bone cells possess functional pathways for both responding to and regulating the uptake of serotonin. Serotonergic receptors have been identified in all the major bone cell types (osteoblasts, osteocytes, and osteoclasts) and stimulation of these receptors influence bone cell activities (Gustafsson et al., 2006).
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