NBME 17 Dopamine β-hydroxylase (NBME Answers)

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submitted by ∗cassdawg(1781)

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Answering this question requires general knowledge of the catecholamine synthesis pathway (FA2020 p83).

The approach I took to this question was mainly elimination of wrong answers:

MAO (monoamine oxidase) could be eliminated because she is lacking epinephrine and since MAO is involved in the breakdown of catecholamines, a deficiency in MAO would increase concentrations of norepinephrine and other catecholamines.
Norepinephrine transporter could be eliminated because inhibition of reuptake of norepinephrine would, again, increase norepinephrine concentrations and she has decreased concentration.
Tyrosine hydroxylase can be eliminated because it is the first step in catecholamine synthesis and required for dopamine synthesis, and as she has increased dopamine this step is not deficient.
Amino acid decarboxylase, or L-amino acid decarboxylase also called DOPA decarboxylase, is also required in dopamine synthesis and can be eliminated because of her increased dopamine concentration.

This leaves the answer, dopamine beta-hydroxylase.

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waitingonprometric Awesome answer, but just to add a bit more about why the correct answer makes sense. Dopamine beta-hydroxylase is the enzyme that converts dopamine to norepinephrine. Therefore, the increase in dopamine conc. when rising from supine to standing, is trying to tell us that her body is ramping up the SNS to compensate for all of the blood rushing to her feet when she stands up. Ramping up the SNS requires production of catecholamines, but without this enzyme, synthesis of NE only gets to the dopamine stage and lots of dopamine backs up behind this enzyme. +15

Perhaps worth noting here is that Dopamine Beta-hydroxylase is a membrane-bound enzyme found in the vesicular membrane. This means that the conversion of Dopamine to Norepinephrine actually occurs within the synaptic vesicle. Norepinephrine is the only transmitter known to be synthesized within synaptic vesicles. This is mentioned in less detail in SketchyPharm 2.2 Indirect Sympathomimetics.

Also, per FA, this reaction requires Vitamin C as a cofactor!

+2/- baja_blast(219)

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