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.