A group of investigators is studying the regulation of catecholamine synthesis in response to severe stress. In the experiments, subject rats are randomly assigned to either an experimental or a control group. The experimental rats undergo resection of the pituitary gland, and the control rats undergo craniotomy without pituitary resection. The experimental animals are subsequently found to have decreased production of epinephrine by the adrenal medulla and cortisol from the adrenal cortex compared with the control animals. Decreased activity of which of the following enzymes is most likely responsible for the lower epinephrine in the experimental animals?

Question

A group of investigators is studying the regulation of catecholamine synthesis in response to severe stress.  In the experiments, subject rats are randomly assigned to either an experimental or a control group.  The experimental rats undergo resection of the pituitary gland, and the control rats undergo craniotomy without pituitary resection.  The experimental animals are subsequently found to have decreased production of epinephrine by the adrenal medulla and cortisol from the adrenal cortex compared with the control animals.  Decreased activity of which of the following enzymes is most likely responsible for the lower epinephrine in the experimental animals?

Quizplus · Accepted Answer

11ec160b_36ce_8cdd_9249_0f22f17299ca_MD0001_00 The 3 main circulating catecholamines are dopamine, norepinephrine, and epinephrine. Norepinephrine and dopamine are produced in the central as well as the peripheral nervous system, whereas epinephrine is predominantly produced in the adrenal medulla. The first step in the synthesis of catecholamines is the conversion of tyrosine to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase. This is the rate-limiting step in the synthesis of catecholamines. DOPA is converted to dopamine by dopa decarboxylase (Choice B), which is then converted to norepinephrine by dopamine beta-hydroxylase (Choice C). In the adrenal medulla, norepinephrine is rapidly converted to epinephrine by phenylethanolamine-N-methyltransferase (PNMT). Expression of PNMT in the adrenal medulla is upregulated by cortisol. Because the venous drainage of the adrenal cortex passes through the adrenal medulla, cortisol concentrations in the medulla can be very high, and PNMT is expressed at a high level. However, following pituitary resection, the loss of ACTH leads to decreased synthesis of cortisol in the adrenal cortex. The result is decreased PNMT activity and reduced conversion of norepinephrine to epinephrine. (Choices A and D) Catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) are responsible for inactivation of catecholamines. COMT converts epinephrine to metanephrine and norepinephrine to normetanephrine; MAO converts metanephrine and normetanephrine to vanillylmandelic acid. (Choices E and G) Tyrosine required for the synthesis of catecholamines is obtained from either dietary intake or by conversion of phenylalanine by phenylalanine hydroxylase in the liver. Deficiency of phenylalanine hydroxylase enzyme causes phenylketonuria. Tyrosine hydroxylase deficiency impairs catecholamine synthesis and causes infantile parkinsonism and progressive encephalopathy. Educational objective: Cortisol increases the conversion of norepinephrine to epinephrine in the adrenal medulla by increasing the expression of phenylethanolamine-N-methyltransferase. __________ References: Stress-triggered changes in peripheral catecholaminergic systems. (http://www.ncbi.nlm.nih.gov/pubmed/24054153)

A Group of Investigators Is Studying the Regulation of Catecholamine