Today’s USMLE® Step 1 question of the day focuses on a young adult diagnosed with maturity onset diabetes of the young (MODY) type 2. Which of the following best describes a key feature of this enzyme? Let’s find out!

Maturity onset diabetes of the young (MODY) type 2 is a consequence of a defective pancreatic enzyme, which normally acts as a glucose sensor, resulting in a mild hyperglycemia.

Which of the following is a characteristic of this pancreatic enzyme

A. It is inhibited by insulin secretion

B. It is found in most tissues of the body

C. It has higher affinity for glucose

D. It converts glucose to glucose-6-phosphate

E. It is stimulated by increased fructose-6-phosphate

Scroll down for the correct answer!

The correct answer to today’s USMLE® Step 1 Question is…

D. It converts glucose to glucose-6-phosphate

Correct: See Main Explanation.

Incorrect Answer Explanations

A. It is inhibited by insulin secretion

Incorrect: Glucokinase, the defective enzyme seen in MODY type 2, is stimulated by insulin secretion.

B. It is found in most tissues of the body

Incorrect: Glucokinase is only found in pancreatic beta cells and liver. In contrast, hexokinase is found in most tissues of the body, except pancreatic beta cells and liver.

C. It has higher affinity for glucose

Incorrect: Glucokinase has a lower glucose affinity (higher Km) than other hexokinases, which allows it to limit the rate of glucose entry into the glycolytic pathway based on blood glucose levels.

E. It is stimulated by increased fructose-6-phosphate

Incorrect: Glucokinase is inhibited by increased fructose-6-phosphate via negative feedback inhibition.

Main Explanation

Glucokinase and hexokinase are enzymes which phosphorylate glucose to glucose-6-phosphate, trapping glucose inside the cell.

Glucokinase is present in hepatocytes of the liver and beta cells of pancreas. Compared to hexokinase, glucokinase has a higher Km (lower binding affinity) and a higher Vmax (increased capacity). Glucokinase is induced by insulin and undergoes negative feedback inhibition by fructose-6-phosphate.

Hexokinase is found in most tissues. Compared to glucokinase, hexokinase has a lower Km (higher binding affinity) and lower Vmax (lower capacity). Notably, the enzyme is not induced by insulin but does undergo negative feedback inhibition by glucose-6-phosphate. 

Comparison table between Hexokinase and Glucokinase.

* **Location:** Hexokinase is found in most tissues except liver and pancreatic beta cells; Glucokinase is found in the liver and pancreatic beta cells.
* **Induced by insulin:** Hexokinase is not induced by insulin; Glucokinase is induced by insulin.
* **Cause of feedback inhibition:** Hexokinase is inhibited by glucose-6-phosphate; Glucokinase is inhibited by fructose-6-phosphate.
* **Affinity for glucose:** Hexokinase has high affinity and is active at low glucose concentrations; Glucokinase has low affinity and is active at high glucose concentrations.

Major Takeaway 

Glucokinase (liver, β cells of pancreas) and hexokinase (other body tissues) are enzymes which phosphorylate glucose to glucose-6-phosphate, trapping glucose inside the cell.

Want to learn more about this topic?

Watch this Osmosis video: Glycolysis

References

  • Bender D.A., & Mayes P.A. (2018). Glycolysis & the oxidation of pyruvate. Rodwell V.W., & Bender D.A., & Botham K.M., & Kennelly P.J., & Weil P(Eds.), Harper’s Illustrated Biochemistry, 31e. McGraw-Hill. 
  • Robblee, J. and Katzberg, H. (12 July 2016). Distinguishing Radiculopathies from Mononeuropathies. Frontiers in Neurology 7(111): 1-5. 

Want more USMLE® Step 1 practice questions? Try Osmosis from Elsevier today! Access your free trial and discover why millions of current and future clinicians and caregivers love learning with us.

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