Catecholamine Biosynthesis Pathway. Hey, everyone, in this lesson, we’re going to talk about catecholamine synthesis. So we’re going to talk about what a catecholamine is, how the catecholamine synthesis pathway operates, including the enzymes required in the pathway. And then finally we’re going to talk about different genetic diseases or disorders that actually this pathway. So I begin. What does a catecholam mean?
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Catecholamines are a class of hormones that play an important role in the body’s response to stress and danger. Catecholamines are produced from the amino acids tyrosine and phenylalanine, both of which are essential for human health. The pathway of catecholamine biosynthesis is complex and includes several steps that need to be properly regulated in order to produce the appropriate level of catecholamines in the body.
Catecholamine Biosynthesis Pathway
The catecholamine biosynthesis pathway is responsible for the production of catecholamines, such as dopamine, norepinephrine, and epinephrine. This pathway begins with the transfer of a methyl group from S-adenosylmethionine to L-tyrosine, followed by the conversion of L-tyrosine to L-dopa.
The catecholamine biosynthesis pathway is responsible for the production of dopamine, norepinephrine, and epinephrine in the brain. The pathway begins with the conversion of tyrosine to L-dopa by tyrosine hydroxylase. Next, L-dopa is converted to dopamine by dopa decarboxylase. Dopamine is then converted to norepinephrine by norepinephrine decarboxylase.
Catecholamine function
Well, a catecholamine is simply a category A plus Amine. So it’s a monoamine and it’s again a catacle group. So it’s a benzene ring with two hydroxyl groups attached plus one Amine group. Now, the catecholamines include dopamine, norepinephrine, and epinephrine. So they’re all variations on the same molecule and they all act as neurotransmitters and hormones, and all are derived from phenylalanine and or Tyranny.
So phenylalanine, as we know, is an essential amino acid, and phenylalanine and Tyranny both can actually be taken up by the diet. Phenylalanine is required from the diet. Tyrosine is actually produced from phenylalanine. We’ll get into that in a bit of detail in the next slide. So it all starts with Phenylalanine.
Phenylalanine is brought in into the body through dietary intake. Now, what happens is it actually undergoes a hydroxylation reaction on the benzene ring to form Tyrosine by the enzyme Phenylalanine hydroxylase. And this step requires tetrahydrobioptrin. And the hydroxyl group actually gets transferred from the Tetrahydrobioptrine and actually gets transferred to the phenylalanine to produce Tyrasine, and the tetrahydrobiopterin becomes dihydrobioptrine. Now, the dihydrobiopterin can actually be recycled back into tetrahydrobioptrin by the enzyme Dihydrobioptrine reductase with the coalfactor NADPH.
Catecholamine synthesis rate-limiting step
Now, just a quick note. 50% of dietary phenylalanine is used for Tyranny synthesis. So Tyranny can come from phenylalanine or can actually come from the diet as well. Now, Tyrosine can actually be shunted into a different pathway. It can actually undergo a transamination reaction via the enzyme Tyrosine transaminase to form four hydroxyphenyl pyruvic acid.
Now, as you can see here, the Amine group from Tyrosine is actually removed and replaced with a ketone, and the four hydroxyphenyl pyruvic acid can actually be used to form fumerate and acetyl acetate for glycogenic or ketogenic reactions. Now, the Tyrosine can also be acted on by the enzyme Tyrosine hydroxylase. Now, Tyrosine hydroxlase. What it’ll do? Is it’ll actually take the Tyrosine and actually hydroxylate it again?
Now, this is when we actually have a catecholamine. And again, this is carried out with the help of tetrahydrobioptrin. So the hydroxyl group gets transferred from the tetrahydrobioptrin onto the Tyranny to form three, four dihydroxy phenylalanine or DOPA. Again, the Tetrahydrobioptin becomes dihydrobotrin and the dihydrobottom can be again recycled back to tetrahydrobioptrin by DHB reductase. Now, once we have DOPA, this can actually be decarboxylated by the enzyme aromatic amino acid decarboxylase.
Metabolism of catecholamines
And again, what is decarboxylation? Well, decarboxylation is just the removal of a CO2 group, and that’s exactly what happens in this reaction. So, as you can see here, you remove the carboxylic acid group from the dihydroxy phenylalanine and you are left with Dopamine. And one last thing about this enzyme. Aromatic amino acidicarboxase, actually requires vitamin B, six or periodoxyl phosphate as a cofactor.
Now, once you have dopamine, dopamine can actually go through another hydroxylation reaction to produce norepinephrine. So the only difference here is you see, there’s a hydroxyl group on another hydroxyl group on norepinephrine, as opposed to dopamine. And again, this is actually carried out by ascorbate or vitamin C. And this is actually ascorbate is actually processed into Dehydro ascorbate in this reaction. So once we have norepinephrine, norepinephrine can actually be methylated by the enzyme phenyl ethanolamine and methyl transphase to form epinephrine.
And this is actually carried out with the help of the cofactor S adeninozomethionine, or Sam. And what happens is Sam will actually donate a methyl group to the norepinephrine to form epinephrine. And in doing so, Sam will actually become acidinozil homocysteine. Now, acidinosyl homocysteine can actually be recycled back into academia zil methionine by the activated methyl cycle. And I’ll show you that in another lesson.
Storage of catecholamines
And as you can see, epinephrine is simply norepinephrine with an additional methyl group attached at the Amine group. So here is the entire catcholamine synthesis pathway in a concise format. So I’m just going to go over what happens in each step once again for clarity. So in the first step from phenylalanine to tyrazine, there’s a hydroxylation step by the enzyme phenylalanine hydroxylase. The next step from tyrazine to DOPA is also another hydroxylation reaction via the enzyme tyrosine hydroxylase.
Then DOPA actually gets decarboxylated to dopamine. So this is actually a decarboxylation reaction. Dopamine goes through another hydroxylation to form norepinephrine, which is another hydroxylation reaction. And then the final reaction in the pathway is norepinephrine to epinephrine by the enzyme phenyl ethanolamine and methyl transferase, which is a methylation step. Now, when we look at these enzymes, there are actually a variety of genetic diseases that actually affect these enzymes in the pathway.
Catecholamine Structure
So starting at the beginning of the pathway, if there’s a mutation in phenylalanine hydroxylase enzyme, this can lead to a condition known as phenylketinoria. Now, phenylketinori is due to a mutation in phenylalanine hydroxylase gene which causes a reduction in this enzyme or reduced activity of this enzyme, leading to toxically high levels of phenylalanine in the body. Now, in the next step, when we have tyrosine, tyrosine can actually be processed by something known as tyrosinase. Now, I didn’t mention this before, but tyrosinase is an enzyme analog of tyrosine hydroxylase, and tyrosinase is actually present in melanocytes. Now, in melanocytes, tyrosine gets processed by tyrosinase into DOPA, the same as we’ve learned before, and then DOPA can actually be processed into melanin.
Now, if there’s a mutation in tyrosinase, what can happen is we get a condition known as albinism. So any mutation in tyrosinase gene can actually cause albinism. If we go further down the pathway, if we see that there’s mutations in the gene encoding dopamine beta hydroxylase, we actually get a condition known as dopamine beta hydroxylase deficiency. And finally when we look at the last enzyme in the pathway phenyl ethanolamine and methyl transferase there has been some evidence suggesting that reduced activity of this enzyme or reduced amount of this enzyme can lead to higher incidences of vitalago and Alzheimer’s disease. Anyways guys that was catecholamine synthesis lesson.
FAQs
What is the pathway to catecholamine synthesis?
What are the three enzymes in the pathway?
What are catecholamines?
What is the Catecholamine Biosynthesis Pathway?
The Catecholamine Biosynthesis Pathway is a metabolic pathway that converts tyrosine to epinephrine and norepinephrine
These two neurotransmitters are?
Conclusion
the catecholamine biosynthesis pathway is a complex process that starts with the synthesis of tyrosine from phenylalanine. Tyrosine is then converted into dopamine and norepinephrine. These neurotransmitters play an important role in mood, energy, and motivation. The pathway is also responsible for the production of other catecholamines, including epinephrine and cortisol. Understanding this pathway is important for understanding how catecholamines are involved in health and disease.
