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Catecholamines like dopamine, noradrenaline and adrenaline are broken down with enzymes that catalyze the reaction. Can they degrade back into tyrosine (a conditionally essential amino acid), or is the synthesis of catecholamines like adrenaline irreversible? (in context human body, but, broadest possible phylogenetic or biochemical context welcome in answer.. )

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  • $\begingroup$ What do you mean by “are broken down with enzymes that catalyse the reaction”? Which reaction? $\endgroup$
    – David
    Jun 11 '20 at 19:22
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A glance at the relevant BioCyc entry tells us that each reaction in the catecholamine biosynthesis pathway is irreversible. The standard free energy change of each reaction—again from BioCyc—is given below.

\begin{array} {|r|r|} \hline \text{Reaction} & \Delta _r G' ^{\circ} \text{ in kcal mol}^{-1}\\ \hline \text{Tyrosine hydroxylation} & -93.0 \\ \hline \text{Decarboxylation of DOPA} & -3.09 \\ \hline \text{Hydroxylation of dopamine} & -67.9 \\ \hline \text{Norepinephrine to epinephrine} & -10.5 \\ \hline \end{array}

Note that all the free energy changes are negative, i.e. all reactions are irreversible under physiologic circumstances. (For the last one, there is a simple explanation: S–adenosylmethionine is a powerful methylator [1].)

Another aspect is worth a mention. Under physiologic conditions, the reversibility of a reaction depends not only on the free energy changes involved, but also on what happens to the reactants and products. A large supply of reactants, or rapid removal of reaction products, can make the reaction physiologically irreversible. Applying this principle to the catecholamine biosynthesis pathway:

  1. A steady supply of oxygen is available from the atmosphere—this drives the tyrosine and dopamine hydroxylation reactions in the forward direction.

  2. The dihydrobiopterin produced by tyrosine hydroxylase is scavenged by reduction to tetrahydrobiopterin, which further takes part in the tyrosine hydroxylase reaction [1].

  3. The carbon dioxide produced by DOPA decarboxylase is exhaled out.

This further adds to irreversibility.

Of course, as mentioned by @user1136 in the comments, it is theoretically possible to have a "reverse" pathway by coupling to ATP hydrolysis. However, I could not find any such pathway in database searches.

Summary: To the best of my knowledge, humans cannot convert catecholamines back to tyrosine.


Reference

  1. Nelson DL, Cox MM. Lehninger principles of biochemistry. 6th ed. New York: WH Freeman and Company; c2013. Chapter 18, Amino acid oxidation and the production of urea; p 695–730.
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  • $\begingroup$ @user1136 True. But I could not find any such reaction for tyrosine. The only reaction in humans that favours tyrosine biosynthesis is (to the best of my knowledge) hydroxylation of phenylalanine. $\endgroup$
    – Adhish
    Apr 19 '20 at 16:33
  • $\begingroup$ @user1136 — The poster asked whether the synthetic pathway was reversible. This answer gives the correct response. Whether there is a pathway for degradation is a completely different matter. I imagine there is, but it is not the reverse of the pathway for synthesis, any more than the reaction of ribonuclease is the reverse of that of RNA polymerase. (No NTPs in the former, in case you hadn’t noticed. $\endgroup$
    – David
    Jun 11 '20 at 19:20
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I do believe it's irreversible. When catecholamines have done their duty, they are degraded by COMT and MAO into products that are excreted in the urine.

I'll make an example out drugs that are MAO inhibitors. The enzyme MAO participates in the degradation of dopamine, NE, and Epi. MAO-A inhibitors are non-selective and used for depression/anxiety because their inhibition will increase levels of dopamine and NE (this might help show that there is no reverse reaction, because we don't see an increase in tyrosine). MAO-B inhibitors are dopamine specific, and therefore used in parkinsons which is a disease of low dopamine.

Hope this helps!

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