A 34-year-old woman is brought to the emergency department in the early morning with confusion, tremor, and sweating. Her husband reports that she did not wake to her alarm clock and was difficult to arouse. Over the past week, the patient has had similar episodes in the morning before eating and after exercise. Past medical history is unremarkable. Blood pressure is 135/95 mm Hg, pulse is 110/min, and respirations are 24/min. The patient is arousable to voice but does not follow commands. Cranial nerve examination, muscle tone, and deep tendon reflexes are normal. A bedside fingerstick glucose level is 35 mg/dL. The patient is given an intravenous infusion of glucose, which rapidly improves her mental status. Further evaluation reveals that her episodes of hypoglycemia are due to increased levels of an endogenous hormone. This hormonal imbalance is most likely causing the patient's symptoms by stimulating which of the following conversions?

Question

A 34-year-old woman is brought to the emergency department in the early morning with confusion, tremor, and sweating.  Her husband reports that she did not wake to her alarm clock and was difficult to arouse.  Over the past week, the patient has had similar episodes in the morning before eating and after exercise.  Past medical history is unremarkable.  Blood pressure is 135/95 mm Hg, pulse is 110/min, and respirations are 24/min.  The patient is arousable to voice but does not follow commands.  Cranial nerve examination, muscle tone, and deep tendon reflexes are normal.  A bedside fingerstick glucose level is 35 mg/dL.  The patient is given an intravenous infusion of glucose, which rapidly improves her mental status.  Further evaluation reveals that her episodes of hypoglycemia are due to increased levels of an endogenous hormone.  This hormonal imbalance is most likely causing the patient's symptoms by stimulating which of the following conversions?

Quizplus · Accepted Answer

11ec160b_36cb_0a68_9249_8959e41306a2_MD0001_00 This patient has developed hypoglycemia secondary to increased levels of an endogenous hormone. Hypoglycemia can develop due to insulin excess (either endogenous [eg, insulinoma] or exogenous [eg, inadvertent overdose, surreptitious insulin/secretagogue use]) as well as deficiency of counterregulatory hormones (eg, glucagon, epinephrine, cortisol). Insulin lowers plasma glucose by increasing glucose uptake in fat, muscle, and liver. In addition, insulin causes an increase in glycolysis by activating phosphofructokinase-2 (PFK2), the enzyme that produces fructose 2,6-bisphosphate. The intracellular concentration of fructose 2,6-bisphosphate is the major regulator of phosphofructokinase-1 (PFK1), which converts fructose 6-phosphate to fructose 1,6-bisphosphate in the rate-limiting step of glycolysis. Fructose 2,6-bisphosphate stimulates PFK1 while inhibiting the reverse enzyme, fructose 1,6-bisphosphatase. As a result, the rise in fructose 2,6-bisphosphate levels caused by insulin leads to an increase in glycolysis and inhibition of gluconeogenesis, with a corresponding decrease in circulating glucose levels. (Choice A) Insulin promotes the storage of glucose by inhibiting glycogen phosphorylase (breaks down glycogen into glucose-6-phosphate) and stimulating glycogen synthase (incorporates UDP-glucose into glycogen). (Choices B, D, and E) Glucose 6-phosphate is converted to fructose 6-phosphate by phosphoglucose isomerase. Fructose 1,6-bisphosphate is converted to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate by fructose bisphosphate aldolase. Glyceraldehyde 3-phosphate is converted to phosphoenolpyruvate through the action of multiple enzymes. These steps are readily reversible and not regulated by insulin. (Choice F) Oxaloacetate is converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase during gluconeogenesis; this reaction is downregulated by high insulin levels. Educational objective: Phosphofructokinase-1 (PFK1) catalyzes the rate-limiting step in glycolysis, and the most potent stimulator of PFK1 is fructose 2,6-bisphosphate. Insulin increases production of fructose 2,6-bisphosphate by phosphofructokinase-2 (PFK2), thereby stimulating glycolysis. __________ References: Roles for fructose-2,6-bisphosphate in the control of fuel metabolism: beyond its allosteric effects on glycolytic and gluconeogenic enzymes. (http://www.ncbi.nlm.nih.gov/pubmed/16860376)

A 34-Year-Old Woman Is Brought to the Emergency Department in the Early