Lesson on Serotonin and Melatonin Synthesis from the amino acid Tryptophan. Tryptophan is an essential amino acid, which is used to produce the monoamine neurotransmitter serotonin and the hormone melatonin. Serotonin is important in regulation of mood, appetite and sleep in the central nervous system, whereas melatonin is produced in the pineal gland and is important in regulating circadian rhythms. In the process of converting tryptophan into serotonin and melatonin, several important cofactors are used including tetrahydrobiopterin, s-adenosyl methionine (SAM), and co-enzyme A. Vitamins B5 and B6 are also required for serotonin and melatonin synthesis.
Hey everyone and this was when i talked about serotonin and melatonin synthesis so in this we’re going to talk about what serotonin and melatonin is actually produced from we’re gonna talk about step by step process by which serotonin melatonin are synthesized we’re gonna talk about enzymes that are involved in their synthesis and we’re gonna talk about important
Cofactors and vitamins that are required in their synthesis so begin serotonin is also known as 5-hydroxytryptamine and it is a mono amine neurotransmitter it’s derived from the amino acid tryptophan we’ll talk about tryptophan in a little bit so serotonin has functions and various sip systems within the body one of those is in the central nervous system it’s
Involved with mood appetite and sleep regulation it’s also important in the gastrointestinal system and in bone metabolism as well so it regulates gi motility in bone metabolism now for melatonin melatonin is also known as n-acetyl v methoxy tryptamine and it’s produced by the pineal gland and it itself regulates sleep and wakefulness now melatonin is a hormone
And it is important in synchronizing the circadian rhythm and melatonin itself is produced from serotonin now with regards to tryptophan we mentioned that tryptophan is an amino acid but tryptophan is actually an essential amino acid and it’s an essential amino acid in humans so that means that we have to get it from our diet so some of the dietary sources of
Trypsin include chocolate milk chickpeas red meat fish in poultry so many different foods that have protein in them actually contain tryptophan so we might hero turkey has tryptophan or chocolate these are a couple of common commonly known sources of tryptophan now if we get tryptophan from our diet from a dietary source like we mentioned before can be acted on
By the enzyme tryptophan hydroxylase tryptophan hydroxylase requires a cofactor known as tetrahydrobiopterin it also requires an oxygen molecule as well now tryptophan hydroxylase can act on tryptophan to produce 5-hydroxytryptophan and in the process it actually processes tetrahydrobiopterin into dihydrate by altering so if we look at the chemical structure
Of 5-hydroxytryptophan and tryptophan we see an important distinction so this hydroxyl group is added to carbon 5 of tryptophan so this tryptophan hydroxylase reaction simply adds a hydroxyl group to the tryptophan to form hydra 5-hydroxytryptophan now die hydra by atre in itself can then be recycled can be recycled by the enzyme die hydra by a parent reductase
Or dhb reductase it utilizes an nadph and nadph is oxidized to nad p+ and in the process da hyderabad current is recycled back into tetrahydrobiopterin so what’s important to note from this step is that a hydroxyl group is added to tryptophan it requires tetrahydrobiopterin as a cofactor and dye hydro operon the product of tetrahydrobiopterin can actually be
Recycled with an nadph utilising the enzyme dhb reductase nadph comes from the pentose phosphate pathway now once we have 5-hydroxytryptophan it can be acted on by the enzyme aromatic l-amino acid decarboxylase so that means as its name suggests it actually deep carboxylates the 5-hydroxytryptophan it removes a carbon dioxide so when it removes a carbon dioxide
From 5-hydroxytryptophan it actually becomes 5-hydroxytryptamine so where does this carbon dioxide actually come from well it actually comes from this portion of 5-hydroxytryptophan so this carboxyl group is removed leaving us with 5-hydroxytryptamine and fly my directory tryptamine is actually serotonin so in two steps we can process tryptophan into serotonin or
5-hydroxytryptamine and these two steps require a hydroxylation step and a decarboxylation step and this enzyme of aromatic amino acid decarboxylase requires an important cofactor known as pyridoxal phosphate which is an active form of vitamin b6 so this enzymatic step requires vitamin b6 so once we have 5ht or serotonin it can be acted on by the enzyme serotonin ns
It’ll transfer these now this enzyme requires acidic way as a cofactor and when serotonin in acetyltransferases acts on 5-hydroxytryptamine as its name suggests it actually transfers in a siddal group from acidic away this leaves us with coenzyme a and hydrogen ion as byproducts the acetyl group from acidic way actually gets added on to 5-hydroxytryptamine actually
Gets attached to the nitrogen group here so we see here now this a sidel group is attached to the 5-hydroxytryptamine giving us n acetyl serotonin which is also known as normal at onin so in essence the acetyl co a acts as a siddall group donor the serotonin in acetyl transferase simply takes an acidic group from acetyl co a adds it on to 5-hydroxytryptamine and
Gives us n acetyl serotonin or nor melatonin once we have nor melatonin it can be acted on by the enzyme n acetyl serotonin o methyl transferase this step requires an important cofactor known as s adenosylmethionine or sin now this enzyme actually transfers a methyl group and what it does is it actually transfers a methyl group from from s-adenosylmethionine to
N-acetyl serotonin it actually adds it on this hydroxyl group here so you can see here that this is an added methyl group this leaves us with the byproduct s-adenosyl homocysteine so one when we actually donate the methyl group from sam we get acid in a zil homocysteine that methyl group gets added to this hydroxyl group this leaves us with melatonin or an acetyl
5mf oxy tryptamine so this is a very important step because it requires this a very important cofactor known as s adenosylmethionine or sam we’ve learned about this before in other previous lessons whereby this cofactor gets generated from the activated methyl cycle so in essence when we get this s-adenosyl homocysteine byproduct it can be recycled through the
Activated methyl cycle to form s adenosylmethionine once again which can be used for other processes so that we’ve gone over the entire pathway let’s review the pathway once again to make sure we remember the important steps and important cofactors in this pathway so the first step of the pathway involves the enzyme tryptophan hydroxylase acting on tryptophan this
Is a hydroxylation step it requires the cofactor tetrahydrobiopterin and this step essentially adds a hydroxyl group to trip’s tryptophan the next step involves the enzyme aromatic amino acid decarboxylase acting on 5-hydroxytryptophan this is a decarboxylation reaction and it involves the enzyme pyridoxal phosphate which is an active form of vitamin b6 and
This reaction removes a carbon dioxide group the next step in the reaction involves the enzyme serotonin n acetyl transferase acting on 5-hydroxytryptamine or 5-ht this is in a situation reaction it requires the cofactor acetyl coenzyme a this essentially acts as an acetyl group donor so acidic away acts as in the civil group donor it donates an acetyl group to
5-hydroxytryptamine to form an acetal serotonin now coenzyme a is a derivative of vitamin b5 or pantothenate so this is an important distinction also that is important to know that we required vitamin b5 for this reaction to take place as well in the last step involves the enzyme n-acetyl serotonin oh methyl transferase so this reaction is a methylation reaction so
It actually adds a methyl group to n acetyl serotonin to form melatonin this requires the cofactor s adenosylmethionine or sam and s adenosylmethionine actually acts as the methyl group donor in this reaction it takes a methyl group and it adds it to normal atonement to form melatonin so there’s a few things i want you to remember from this pathway one is that we
Require vitamin b6 for this synthesis of serotonin and melatonin we require vitamin b5 in the form of coenzyme a for the synthesis of melatonin and we require methionine the amino acid methionine in the form of s adenosylmethionine for the production of melatonin once again so there’s a few things we need from this entire pathway vitamin b6 vitamin b5 and methionine
So thank you so much for watching that was a lesson on serotonin and melatonin synthesis i hope you found this lesson helpful if you did please like and subscribe for more videos like this one and as always again thank you so much for watching and i hope to see you next time
Transcribed from video
Serotonin and Melatonin Synthesis | Tryptophan Metabolism By JJ Medicine
