A 72-year-old woman is brought to the emergency department after lying on the floor in her home for the past 2 days. The patient's neighbor called police after phone calls were not answered and no one opened the door. She was found awake on the bathroom floor lying in feces and urine. The patient says she fell and injured her right hip and was unable to get up to call for help. She did not eat or drink anything during that time. On examination, the patient appears dehydrated and has right hip tenderness. Laboratory studies show serum glucose of 72 mg/dL and positive urine ketones. Radiographs of the right hip show a right femoral neck fracture. Increased activity of which of the following enzymes is most likely contributing to both the serum and urine laboratory findings?

Question

A 72-year-old woman is brought to the emergency department after lying on the floor in her home for the past 2 days.  The patient's neighbor called police after phone calls were not answered and no one opened the door.  She was found awake on the bathroom floor lying in feces and urine.  The patient says she fell and injured her right hip and was unable to get up to call for help.  She did not eat or drink anything during that time.  On examination, the patient appears dehydrated and has right hip tenderness.  Laboratory studies show serum glucose of 72 mg/dL and positive urine ketones.  Radiographs of the right hip show a right femoral neck fracture.  Increased activity of which of the following enzymes is most likely contributing to both the serum and urine laboratory findings?

Quizplus · Accepted Answer

11ec160b_36d0_3a91_9249_a1eb9cc54bc4_MD0001_00 This patient's laboratory studies show the presence of ketones in the urine and maintenance of fasting blood glucose values in the low-normal range despite prolonged fasting. Hormone-sensitive lipase (HSL) is an enzyme found in adipose tissue that catalyzes the mobilization of stored triglycerides into free fatty acids (FFAs) and glycerol. HSL is activated in response to stress hormones (eg, catecholamines, glucagon, ACTH), whereas it is inhibited by the release of insulin. The stress hormones stimulate Gs protein-coupled receptors on adipocytes, leading to increased cAMP production and activation of protein kinase A (PKA). Finally, PKA phosphorylates and activates HSL, stimulating lipolysis. FFAs and glycerol released into the circulation can be taken up by the liver, where the glycerol is used primarily as a carbon source for gluconeogenesis. The liver oxidizes the FFAs to acetyl-coA, which can then be further metabolized to ketone bodies (eg, acetoacetate, beta-hydroxybutyrate) or shunted into the TCA cycle to generate energy for gluconeogenesis. During starvation, most tissues utilize a combination of FFAs and ketones for their energy needs. Important exceptions include the brain (FFAs do not cross the blood-brain barrier, so only ketone bodies/glucose can be used) and erythrocytes (can use only glucose due to lack of mitochondria). (Choice A) Glycogen phosphorylase is the rate-limiting enzyme in glycogenolysis, a process that frees glucose-1-phosphate from stored glycogen chains. Glycogenolysis increases blood glucose levels during the first several hours of fasting but has no effect on fatty acid oxidation. (Choice C) Lipoprotein lipase is an enzyme found on endothelial cells that functions to degrade triglycerides found in chylomicrons and VLDL. Although it is functionally similar to HSL, it works in the bloodstream to form FFAs that are then transported into adipocytes storage or used by tissues (eg, heart/skeletal muscle) for energy production. (Choice D) Mitochondrial HMG-CoA synthase plays a role in the production of ketones. Although it could be responsible for the presence of urinary ketone bodies in this patient, it would not account for the maintenance of blood glucose levels. (Choice E) Phosphofructokinase-1 catalyzes the major rate-limiting step in glycolysis by converting fructose-6-phosphate to fructose-1,6-bisphosphate. It is not involved in gluconeogenesis or ketone production. Educational objective: Hormone-sensitive lipase is found in adipose tissue, where it functions to drive the breakdown of stored triglycerides into free fatty acids and glycerol. During times of starvation, this enzyme provides substrates for hepatic gluconeogenesis and ketone body formation. __________ References: Lipolysis: more than just a lipase. (http://www.ncbi.nlm.nih.gov/pubmed/12810703)

A 72-Year-Old Woman Is Brought to the Emergency Department After