Choose the ONE best answer.
3.1. In preparation for a trip to an area of India where chloroquine-resistant malaria is endemic, a young man is given primaquine prophylactically. Soon thereafter, he develops a hemolytic condition due to a deficiency in glucose 6-phosphate dehydrogenase. A less-than-normal level of which of the following is a consequence of the enzyme deficiency and the underlying cause of the hemolysis?
A. Glucose 6-phosphate
B. Oxidized form of nicotinamide adenine dinucleotide
C. Reduced form of glutathione D. Ribose 5-phosphate
Correct answer = C. Glutathione (G-SH) is essential for red cell integrity and is maintained in this reduced (functional) form by nicotinamide adenine dinucleotide phosphate (NADPH)-dependent glutathione reductase. The NADPH is from the oxidative portion of the pentose phosphate pathway. Individuals with a deficiency of the regulated enzyme of this pathway, glucose 6-phosphate dehydrogenase (G6PD), have a decreased ability to generate NADPH and, therefore, a decreased ability to keep G-SH reduced. When treated with an oxidant drug such as primaquine, some patients with G6PD deficiency develop a hemolytic anemia. Primaquine does not affect glucose 6phosphate levels. Nicotinamide adenine dinucleotide (NAD[H]) is neither produced by the pathway nor used as a coenzyme by G-SH reductase. A decrease in ribose 5-phosphate does not cause hemolysis.
3.2. Septic shock, a state of acute circulatory failure characterized by persistent arterial hypotension (low blood pressure) and inadequate organ perfusion refractory to fluid resuscitation, results from a severe inflammatory response to bacterial infection. It has a high mortality rate and is associated with changes in the level of nitric oxide. Which statement concerning septic shock is most likely correct?
A. Activation of endothelial nitric oxide synthase causes an increase in nitric oxide.
B. High mortality is the result of the long half-life of nitric oxide.
C. Lysine, the nitrogen source for nitric oxide synthesis, is deaminated by bacteria.
D. Overproduction of nitric oxide by a calcium-independent enzyme is the cause of the hypotension.
Correct answer = D. Overproduction of short-lived (not long-lived) nitric oxide (NO) by calcium-independent, inducible nitric oxide synthase (iNOS) results in excessive vasodilation leading to hypotension. The endothelial enzyme (eNOS) is constitutive and produces low levels of NO at a consistent rate. NOS use arginine, not lysine, as the source of the nitrogen.
3.3. An individual who has recently been prescribed a drug (atorvastatin) to lower cholesterol levels is advised to limit consumption of grapefruit juice, because high intake of the juice reportedly results in an increased level of the drug in the blood, increasing the risk of side effects. Atorvastatin is a substrate for the cytochrome P450 enzyme CYP3A4, and grapefruit juice inhibits the enzyme. Which statement concerning CYP enzymes is most likely correct? They:
A. accept electrons from reduced nicotinamide adenine dinucleotide.
B. catalyze the hydroxylation of hydrophobic molecules.
C. differ from nitric oxide synthase in that they contain heme.
D. function in association with an oxidase.