An 18-year-old girl with a history of type 1 diabetes mellitus comes to the emergency department after several hours of nausea, vomiting, and abdominal pain. The patient reports that she is on vacation visiting friends and has not taken insulin in the last 2 days. Physical examination shows breath with fruity odor and dry mucosal membranes. Laboratory studies show a blood glucose level of 452 mg/dL and high anion gap metabolic acidosis. Urinalysis is positive for ketones. It is determined that the patient's insulin deficiency is causing increased production of gluconeogenic precursors that are subsequently converted to glucose in the liver. Which of the following enzymes is most likely to provide these precursor substrates?

Question

An 18-year-old girl with a history of type 1 diabetes mellitus comes to the emergency department after several hours of nausea, vomiting, and abdominal pain.  The patient reports that she is on vacation visiting friends and has not taken insulin in the last 2 days.  Physical examination shows breath with fruity odor and dry mucosal membranes.  Laboratory studies show a blood glucose level of 452 mg/dL and high anion gap metabolic acidosis.  Urinalysis is positive for ketones.  It is determined that the patient's insulin deficiency is causing increased production of gluconeogenic precursors that are subsequently converted to glucose in the liver.  Which of the following enzymes is most likely to provide these precursor substrates?

Quizplus · Accepted Answer

11ec160b_36cf_ec70_9249_a51aa68b4a70_MD0001_00 This patient in diabetic ketoacidosis is experiencing increased triglyceride breakdown in adipose tissue due to her insulin deficiency. Triglycerides stored in adipose tissue are metabolized to free fatty acids and glycerol by hormone-sensitive lipase in response to low insulin and high catecholamine levels. Adipocytes are unable to metabolize glycerol, so it is secreted into the circulation and transported to the liver, where it is phosphorylated to glycerol-3-phosphate by glycerol kinase. Glycerol-3-phosphate is subsequently converted by glycerol-3-phosphate dehydrogenase to dihydroxyacetone phosphate (DHAP), which can be used to produce glucose through gluconeogenesis. (Choice A) Acetyl CoA carboxylase is a biotin-dependent enzyme present in both liver and adipose tissues. It catalyzes the first committed step in fatty acid synthesis, the conversion of acetyl CoA to malonyl CoA. (Choice B) Fatty acids must first be activated by acyl CoA synthetase in the cytoplasm in order to undergo beta-oxidation in mitochondria. Although beta-oxidation of fatty acids is increased in diabetic ketoacidosis, the resulting acetyl-CoA is used for energy and ketone body formation (not glucose production). (Choice C) In contrast to fatty acid oxidation, which occurs in mitochondria, fatty acid synthesis occurs in the cytosol. Acetyl CoA generated in mitochondria during glycolysis is transferred to the cytosol as citrate. In the cytoplasm, ATP citrate lyase converts citrate back into acetyl CoA that can be used for fatty acid chain elongation. (Choice D) Glucose-6-phosphate dehydrogenase is the first enzyme of the hexose monophosphate (HMP) shunt. The HMP shunt produces pentose sugars for nucleotide synthesis and NADPH, which is necessary for cholesterol and fatty acid biosynthesis. Educational objective: Glycerol produced by the degradation of triglycerides in adipose tissue can be used by glycerol kinase in the liver and kidney to synthesize glucose during gluconeogenesis.

An 18-Year-Old Girl with a History of Type 1 Diabetes