Serotonin 122
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Serotonin
Introduction.
In animals & unicellular organisms.
Anatomy.
Biosynthesis.
Metabolism.
Function.
Serotonin receptors & the mechanism of action.
Pathology & Increasing serotonin levels.
Drugs targeting the 5 –HT system.
References & External links.
Serotonin Introduction
Widely distributed amine (animals + plants). Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized In humans.
Serotonin is present in GI enterochromaffin cells (90%), platelets , CNS (raphe nuclei of brain stem )& pineal gland (precursor of melatonin).
Synthesized from tryptophan (in diet) in two steps.
Serotonin
Introduction - Platelets do not synthesize but take up from blood (active uptake process in platelets and nerve terminals). - Cell storage in granules similar to catecholamines . - Serotonin is also found in many mushrooms and plants, including fruits and vegetables.
Serotonin
In animals& In unicellular organisms
Serotonin as a neurotransmitter is found in many animals, including insects. The gastrointestinal parasite Entamoeba histolytica secretes serotonin, causing a sustained secretory diarrhea in some patients. Patients infected with Entamoeba histolytica have been found to have highly elevated serum serotonin levels which returned to normal following resolution of the infection. Entamoeba histolytica also responds to the presence of serotonin by becoming more virulent .
Serotonin Anatomy in the brain Gross Anatomy.
Micro Anatomy.
Serotonin Anatomy
Gross Anatomy
The neurons of the raphe nuclei are the principal source of 5-HT release in the brain.
The raphe nuclei are neurons grouped into about nine pairs and distributed along the entire length of the brainstem, centered around the reticular formation.
Axons from the neurons of the raphe nuclei form a neurotransmitter system, reaching large areas of the brain.
Axons of neurons in the caudal raphe nuclei terminate in the following locations: Deep cerebellar nuclei Cerebellar cortex Spinal cord
Serotonin Anatomy Gross Anatomy On the other hand, axons of neurons in the rostral raphe nuclei terminate in e.g.: Thalamus Striatum Hypothalamus Nucleus accumbens Neocortex Cingulate gyrus Cingulum Hippocampus Amygdala Thus, activation of this serotonin system has effects on large areas of the brain
Serotonin Anatomy
Microanatomy
Serotonin is released from serotonergic varicosities (swellings) into the extra neuronal space, but not from synaptic terminal boutons as other neurotransmitters.
Serotonin diffuses over a relatively wide gap (>20µm) to activate 5-HT receptors located on the dendrites, cell bodies and presynaptic terminals of adjacent neurons .
Serotonin Biosynthesis
A hydroxyl-group at carbon 5 of the carbon skeleton of L- tryptophan without a carboxyl group gives serotonin its descriptive chemical name, 5-hydroxytryptamine.
Serotonin Biosynthesis
Serotonin Biosynthesis
In animals including humans, serotonin is synthesized from the amino acid L- tryptophan by a short metabolic pathway consisting of two enzymes: tryptophan hydroxylase (TPH) and amino acid decarboxylase (AAD)
The TPH-mediated reaction is the rate-limiting step in the pathway. TPH has been shown to exist in two forms: TPH1, found in several tissues, and TPH2, which is a brain-specific isoform.
5-OHTr decarboxylase same as DOPA decarboxylase.
Serotonin Biosynthesis
There is also evidence that ovarian hormones can affect the expression of TPH in various species, suggesting a possible mechanism for postpartum depression and premenstrual stress syndrome .
Serotonin biosynthesis in plants likewise begins with Ltryptophan, which is however first decarboxylated by tryptophan decarboxylase to give tryptamine, which is then hydroxylated by the cytochrome P450 monooxygenase, tryptamine 5-hydroxylase, yielding serotonin.
Serotonin Biosynthesis
Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system because it does not cross the blood-brain barrier.
However, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is synthesized, can and do cross the blood-brain barrier.
These agents are available as dietary supplements and may be effective serotonergic agents .
Serotonin Metabolism
One product of serotonin breakdown is 5-Hydroxyindoleacetic acid (5 HIAA), which is excreted in the urine.
Serotonin and 5 HIAA are sometimes produced in excess amounts by certain tumors or cancers, and levels of these substances may be measured in the urine to test for these tumors.
No end-product negative feedback.
Serotonin
Function
In the central nervous system, serotonin plays
an important role as a neurotransmitter in the modulation of anger, aggression, body temperature, mood, sleep, human sexuality, appetite, and metabolism, as well as stimulating vomiting .
Serotonin Function In the C.N.S Pain perception Sleep/Wakefulness Various behaviors normal/abnormal: depression, schizophrenia, obsessive compulsive behavior, etc. Neuroendocrine regulation – controls hypothalamic cells involved in release of several anterior pituitary hormones.
Serotonin Function
In addition, serotonin is also a peripheral signal mediator. It is found extensively in the human gastrointestinal tract as about 80-90% of the body's total serotonin is found in the enterochromaffin cells in the gut.
In the blood, the major storage site is platelets, which collect serotonin for use in mediating post-injury vasoconstriction .
Serotonin Function
Precursor of melatonin hormone secreted by the pineal gland in proportion to the body's exposure to light, hormone that is essential in the regulation of biological rhythms (sleep, mood, puberty, and menstrual cycles).
Recent research suggests that serotonin plays an important role in liver regeneration and acts as a mitogen (induces cell division) throughout the body. Recent research also suggests that intestinal serotonin may inhibit bone formation
Serotonin Serotonin Receptors
5-HT receptors are the receptors for serotonin.
They are located on the cell membrane of nerve cells and other cell types in animals and mediate the effects of serotonin.
Serotonin Serotonin Receptors With the exception of the 5-HT3 receptor, a ligand gated ion channel, all other 5-HT receptors are G protein coupled seven transmembrane (or heptahelical) receptors that activate an intracellular second messenger cascade.
Serotonin Serotonin Receptors
Serotonin Serotonin Receptors
Serotonin Increasing serotonin levels
Serotonin levels can not be increased by diet or supplements of tryptophan. For example, increasing foods rich in tryptophan (eg, meats, proteins) does not increase serotonin levels, due to competition with other amino acids. What is required to increase serotonin production is an increase in the ratio of tryptophan to phenylalanine and leucine. Fruits with a good ratio include dates, papaya and banana. Foods with a lower ratio inhibit the production of serotonin. These include whole wheat and rye bread .
Serotonin Increasing serotonin levels Much research has indicated that vigorous aerobic exercise improves mood, believed to be facilitated by an increase in serotonin levels. Research also suggests that eating a diet rich in whole grain carbohydrates and low in protein will increase serotonin by secreting insulin, which helps in amino acid competition.
Serotonin Increasing serotonin levels It
is also believed that muscles use many of the amino acids except tryptophan, allowing men to have more serotonin than women.
Serotonin
Pathology If
neurons that make serotonin — serotonergic neurons — are abnormal in infants, there is a risk of sudden infant death syndrome (SIDS).
Serotonin Pathology
Serotonin syndrome Overstimulation of central & peripheral serotonin receptors. this may be occurred due to increasing of stretonergic medications prescriptions.
Serotonin Pathology
Serotonin syndrome Laboratory
Abnormalities
1. Metabolic acidosis. 2. rhabdomyolosis (disintegration of skeletal muscle tissue as a result of electrocution or prolonged exposure to toxins (characterized by excretion of myoglobin in the urine)
3.Elevated serum aminotransferase &
creatine.
Serotonin Pathology
Serotonin syndrome
Serotonin Pathology
Chronic diseases resulting from serotonin 5-HT2B overstimulation
overdoses of serotonin, or serotonin agonist drugs, may cause acute or chronic pulmonary hypertension from pulmonary vasoconstriction, or else syndromes of retroperitoneal fibrosis or cardiac valve fibrosis (endocardial fibrosis) from overstimulation of serotonic growth receptors on fibrocytes .
Serotonin Pathology Chronic diseases resulting from serotonin 5-HT2B overstimulation
Serotonin itself may cause a syndrome of cardiac fibrosis when it is eaten in large quantities in the diet (the Matoki banana of East Africa) or when it is over-secreted by certain mid-gut carcinoid tumors.
The valvular fibrosis in such cases is typically on the right side of the heart, since excess serotonin in the serum outside platelets is metabolized in the lungs, and does not reach the left circulation.
Serotonin Drugs targeting the 5-HT system Several
classes of drugs target the 5-HT system including some antidepressants, antipsychotics, anxiolytics, antiemetics, and antimigraine drugs as well as the psychedelic drugs and empathogens.
References & External links
From Wikipedia .com, the free encyclopedia. Scribd.com. Handbook of endocrinology. Textbook of biochemistry with clinical correlations. Harper’s biochemistry & lehninger biochemistry. Other search websites (yahoo, google & 4shared)
[email protected]
Introduction.
In animals & unicellular organisms.
Anatomy.
Biosynthesis.
Metabolism.
Function.
Serotonin receptors & the mechanism of action.
Pathology & Increasing serotonin levels.
Drugs targeting the 5 –HT system.
References & External links.
Serotonin Introduction
Widely distributed amine (animals + plants). Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized In humans.
Serotonin is present in GI enterochromaffin cells (90%), platelets , CNS (raphe nuclei of brain stem )& pineal gland (precursor of melatonin).
Synthesized from tryptophan (in diet) in two steps.
Serotonin
Introduction - Platelets do not synthesize but take up from blood (active uptake process in platelets and nerve terminals). - Cell storage in granules similar to catecholamines . - Serotonin is also found in many mushrooms and plants, including fruits and vegetables.
Serotonin
In animals& In unicellular organisms
Serotonin as a neurotransmitter is found in many animals, including insects. The gastrointestinal parasite Entamoeba histolytica secretes serotonin, causing a sustained secretory diarrhea in some patients. Patients infected with Entamoeba histolytica have been found to have highly elevated serum serotonin levels which returned to normal following resolution of the infection. Entamoeba histolytica also responds to the presence of serotonin by becoming more virulent .
Serotonin Anatomy in the brain Gross Anatomy.
Micro Anatomy.
Serotonin Anatomy
Gross Anatomy
The neurons of the raphe nuclei are the principal source of 5-HT release in the brain.
The raphe nuclei are neurons grouped into about nine pairs and distributed along the entire length of the brainstem, centered around the reticular formation.
Axons from the neurons of the raphe nuclei form a neurotransmitter system, reaching large areas of the brain.
Axons of neurons in the caudal raphe nuclei terminate in the following locations: Deep cerebellar nuclei Cerebellar cortex Spinal cord
Serotonin Anatomy Gross Anatomy On the other hand, axons of neurons in the rostral raphe nuclei terminate in e.g.: Thalamus Striatum Hypothalamus Nucleus accumbens Neocortex Cingulate gyrus Cingulum Hippocampus Amygdala Thus, activation of this serotonin system has effects on large areas of the brain
Serotonin Anatomy
Microanatomy
Serotonin is released from serotonergic varicosities (swellings) into the extra neuronal space, but not from synaptic terminal boutons as other neurotransmitters.
Serotonin diffuses over a relatively wide gap (>20µm) to activate 5-HT receptors located on the dendrites, cell bodies and presynaptic terminals of adjacent neurons .
Serotonin Biosynthesis
A hydroxyl-group at carbon 5 of the carbon skeleton of L- tryptophan without a carboxyl group gives serotonin its descriptive chemical name, 5-hydroxytryptamine.
Serotonin Biosynthesis
Serotonin Biosynthesis
In animals including humans, serotonin is synthesized from the amino acid L- tryptophan by a short metabolic pathway consisting of two enzymes: tryptophan hydroxylase (TPH) and amino acid decarboxylase (AAD)
The TPH-mediated reaction is the rate-limiting step in the pathway. TPH has been shown to exist in two forms: TPH1, found in several tissues, and TPH2, which is a brain-specific isoform.
5-OHTr decarboxylase same as DOPA decarboxylase.
Serotonin Biosynthesis
There is also evidence that ovarian hormones can affect the expression of TPH in various species, suggesting a possible mechanism for postpartum depression and premenstrual stress syndrome .
Serotonin biosynthesis in plants likewise begins with Ltryptophan, which is however first decarboxylated by tryptophan decarboxylase to give tryptamine, which is then hydroxylated by the cytochrome P450 monooxygenase, tryptamine 5-hydroxylase, yielding serotonin.
Serotonin Biosynthesis
Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system because it does not cross the blood-brain barrier.
However, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is synthesized, can and do cross the blood-brain barrier.
These agents are available as dietary supplements and may be effective serotonergic agents .
Serotonin Metabolism
One product of serotonin breakdown is 5-Hydroxyindoleacetic acid (5 HIAA), which is excreted in the urine.
Serotonin and 5 HIAA are sometimes produced in excess amounts by certain tumors or cancers, and levels of these substances may be measured in the urine to test for these tumors.
No end-product negative feedback.
Serotonin
Function
In the central nervous system, serotonin plays
an important role as a neurotransmitter in the modulation of anger, aggression, body temperature, mood, sleep, human sexuality, appetite, and metabolism, as well as stimulating vomiting .
Serotonin Function In the C.N.S Pain perception Sleep/Wakefulness Various behaviors normal/abnormal: depression, schizophrenia, obsessive compulsive behavior, etc. Neuroendocrine regulation – controls hypothalamic cells involved in release of several anterior pituitary hormones.
Serotonin Function
In addition, serotonin is also a peripheral signal mediator. It is found extensively in the human gastrointestinal tract as about 80-90% of the body's total serotonin is found in the enterochromaffin cells in the gut.
In the blood, the major storage site is platelets, which collect serotonin for use in mediating post-injury vasoconstriction .
Serotonin Function
Precursor of melatonin hormone secreted by the pineal gland in proportion to the body's exposure to light, hormone that is essential in the regulation of biological rhythms (sleep, mood, puberty, and menstrual cycles).
Recent research suggests that serotonin plays an important role in liver regeneration and acts as a mitogen (induces cell division) throughout the body. Recent research also suggests that intestinal serotonin may inhibit bone formation
Serotonin Serotonin Receptors
5-HT receptors are the receptors for serotonin.
They are located on the cell membrane of nerve cells and other cell types in animals and mediate the effects of serotonin.
Serotonin Serotonin Receptors With the exception of the 5-HT3 receptor, a ligand gated ion channel, all other 5-HT receptors are G protein coupled seven transmembrane (or heptahelical) receptors that activate an intracellular second messenger cascade.
Serotonin Serotonin Receptors
Serotonin Serotonin Receptors
Serotonin Increasing serotonin levels
Serotonin levels can not be increased by diet or supplements of tryptophan. For example, increasing foods rich in tryptophan (eg, meats, proteins) does not increase serotonin levels, due to competition with other amino acids. What is required to increase serotonin production is an increase in the ratio of tryptophan to phenylalanine and leucine. Fruits with a good ratio include dates, papaya and banana. Foods with a lower ratio inhibit the production of serotonin. These include whole wheat and rye bread .
Serotonin Increasing serotonin levels Much research has indicated that vigorous aerobic exercise improves mood, believed to be facilitated by an increase in serotonin levels. Research also suggests that eating a diet rich in whole grain carbohydrates and low in protein will increase serotonin by secreting insulin, which helps in amino acid competition.
Serotonin Increasing serotonin levels It
is also believed that muscles use many of the amino acids except tryptophan, allowing men to have more serotonin than women.
Serotonin
Pathology If
neurons that make serotonin — serotonergic neurons — are abnormal in infants, there is a risk of sudden infant death syndrome (SIDS).
Serotonin Pathology
Serotonin syndrome Overstimulation of central & peripheral serotonin receptors. this may be occurred due to increasing of stretonergic medications prescriptions.
Serotonin Pathology
Serotonin syndrome Laboratory
Abnormalities
1. Metabolic acidosis. 2. rhabdomyolosis (disintegration of skeletal muscle tissue as a result of electrocution or prolonged exposure to toxins (characterized by excretion of myoglobin in the urine)
3.Elevated serum aminotransferase &
creatine.
Serotonin Pathology
Serotonin syndrome
Serotonin Pathology
Chronic diseases resulting from serotonin 5-HT2B overstimulation
overdoses of serotonin, or serotonin agonist drugs, may cause acute or chronic pulmonary hypertension from pulmonary vasoconstriction, or else syndromes of retroperitoneal fibrosis or cardiac valve fibrosis (endocardial fibrosis) from overstimulation of serotonic growth receptors on fibrocytes .
Serotonin Pathology Chronic diseases resulting from serotonin 5-HT2B overstimulation
Serotonin itself may cause a syndrome of cardiac fibrosis when it is eaten in large quantities in the diet (the Matoki banana of East Africa) or when it is over-secreted by certain mid-gut carcinoid tumors.
The valvular fibrosis in such cases is typically on the right side of the heart, since excess serotonin in the serum outside platelets is metabolized in the lungs, and does not reach the left circulation.
Serotonin Drugs targeting the 5-HT system Several
classes of drugs target the 5-HT system including some antidepressants, antipsychotics, anxiolytics, antiemetics, and antimigraine drugs as well as the psychedelic drugs and empathogens.
References & External links
From Wikipedia .com, the free encyclopedia. Scribd.com. Handbook of endocrinology. Textbook of biochemistry with clinical correlations. Harper’s biochemistry & lehninger biochemistry. Other search websites (yahoo, google & 4shared)
[email protected]
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