D. Catechol-O-methyltransferase (COMT) methylation is responsible for breaking down epinephrine and norepinephrine (NE), resulting in the production of metanephrine from epinephrine and normetanephrine from NE (refer to figure on the right). Both of these byproducts are then deaminated by monoamine oxidase (MAO) to form vanillylmandelic acid. The synthesis of catecholamines begins with the hydroxylation of tyrosine, which is converted to 3,4-dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase, a process that requires tetrahydrobiopterin. DOPA is then decarboxylated by a pyridoxal phosphate-requiring decarboxylase to form dopamine. Methylation using S-adenosylmethionine leads to the conversion of NE to epinephrine.

A. NE serves as a neurotransmitter released from the sympathetic nervous system and acts on postsynaptic neurons, causing an increase in heart rate. It is also released from the adrenal medulla and, along with epinephrine, functions as a counterregulatory hormone that mobilizes stored fuels such as glucose and triacylglycerols. These effects are mediated by the binding of NE to adrenergic receptors, which are plasma membrane G protein-coupled receptors. It should be noted that NE does not bind to nuclear receptors like steroid hormones or membrane tyrosine kinase receptors like insulin. Septic shock, characterized by vasodilatory hypotension (low blood pressure due to blood vessel dilation), is caused by the excessive production of nitric oxide by inducible nitric oxide synthase in response to infection. NE binding to receptors on smooth muscle cells causes vasoconstriction, thereby increasing blood pressure.

D. The DNA lesions induced by ultraviolet (UV) radiation are pyrimidine dimers. These dimers are repaired through a process called nucleotide excision repair (NER), which involves the excision of an oligonucleotide containing the dimer followed by replacement of the oligonucleotide. This repair mechanism is present in both prokaryotes and eukaryotes. While no repair system is completely error-free, homologous recombination (HR) for double-strand break repair is less prone to errors compared to nonhomologous end joining (NHEJ) because any lost DNA is replaced. Mismatched-base repair (MMR) involves the identification and repair of the newly synthesized (daughter) strand, with strand methylation being used as a discrimination factor in prokaryotes. Base excision repair (BER) is the mechanism used to remove uracil from DNA, and it involves the action of a glycosylase to remove the base, resulting in the creation of an apyrimidinic or apurinic (AP) site. The sugar-phosphate backbone is then removed through the actions of an endo- and exonuclease.
Answer = D. Degradation of both epinephrine and norepinephrine (NE) involves methylation by catechol-O-methyltransferase (COMT) that produces normetanephrine from NE and metanephrine from epinephrine (see figure at right). Both of these products are deaminated to vanillylmandelic acid by monoamine oxidase (MAO). The substrate for the synthesis of the catecholamines is tyrosine, which gets hydroxylated to 3,4dihydroxyphenylalanine (DOPA) by tetrahydrobiopterin-requiring tyrosine hydroxylase. DOPA is converted to dopamine by a pyridoxal phosphate– requiring decarboxylase. [Note: Most carboxylases require biotin.] NE is converted to epinephrine by methylation, and S-adenosylmethionine provides the methyl group.
Answer = A. NE released from the sympathetic nervous system functions as a neurotransmitter that acts on postsynaptic neurons and causes, for example, increased heart rate. It is also released from the adrenal medulla and, along with epinephrine, functions as a counterregulatory hormone that results in mobilization of stored fuels (for example, glucose and triacylglycerols). These actions are mediated by the binding of NE to adrenergic receptors, which are G protein–coupled receptors of the plasma membrane, and not to nuclear receptors like those of steroid hormones or membrane tyrosine kinase receptors like that of insulin. Septic shock is vasodilatory hypotension (low blood pressure caused by blood vessel dilation) resulting from the production of large amounts of nitric oxide by inducible nitric oxide synthase in response to infection. NE bound to receptors on smooth muscle cells causes vasoconstriction and, thus, raises blood pressure.
Case 5: Sun Sensitivity with Xeroderma Pigmentosum
Answer = D. Pyrimidine dimers are the characteristic DNA lesions caused by ultraviolet (UV) radiation. Their repair involves the excision of an oligonucleotide containing the dimer and replacement of that oligonucleotide, a process known as nucleotide excision repair (NER). (See figure at right for a representation of the process in prokaryotes.) DNA repair systems are found in prokaryotes and eukaryotes. Nothing is error free, but the homologous recombination (HR) method of double-strand break repair is much less prone to error than is the nonhomologous end joining (NHEJ) method because any DNA that was lost is replaced. Mismatched-base repair (MMR) involves identification and repair of the newly synthesized (daughter) strand. In prokaryotes, the extent of strand methylation is used to discriminate between the strands. Base excision repair (BER), the mechanism by which uracil is removed from DNA, utilizes a glycosylase to remove the base, creating an apyrimidinic or apurinic (AP) site. The sugar-phosphate is then removed by the actions of an endo-and exonuclease.