What is a key feature of hexokinase (enzyme involved in glucose metabolism)?

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Characteristics of Hexokinase

Hexokinase is characterized by having a low Km (high affinity for glucose), which is the correct answer to this question.

Key Features of Hexokinase

Hexokinase is a critical enzyme in glucose metabolism that catalyzes the first step of glycolysis by phosphorylating glucose to glucose-6-phosphate using ATP as a phosphoryl donor. Understanding its properties is essential for comprehending cellular energy metabolism.

Affinity for Glucose (Km)

  • Low Km value: Hexokinase has a high affinity for glucose, allowing it to function efficiently even at low glucose concentrations 1
  • This property enables cells to effectively utilize glucose for energy production even when glucose levels are relatively low
  • The low Km is a critical adaptation that ensures priority access to glucose for vital tissues

Regulatory Properties

  • Product inhibition: Hexokinase is inhibited by its product, glucose-6-phosphate 2
  • This feedback inhibition serves as an important regulatory mechanism to prevent excessive phosphorylation of glucose when glucose-6-phosphate accumulates
  • Unlike glucokinase (hexokinase IV), hexokinase is not directly regulated by insulin 3

Tissue Distribution

  • Hexokinase is widely distributed throughout body tissues, not limited to liver and pancreatic islet cells
  • It is particularly abundant in tissues with high energy demands such as brain, muscle, and heart
  • This contrasts with glucokinase (hexokinase IV), which is primarily found in liver and pancreatic β-cells 3

Catalytic Efficiency

  • While hexokinase has a high affinity for glucose (low Km), it has a relatively low Vmax compared to glucokinase
  • This means that while it can function at low glucose concentrations, it reaches saturation quickly and cannot increase its activity proportionally at high glucose concentrations 1

Substrate Specificity

  • Hexokinase can phosphorylate several hexoses beyond glucose, including mannose, fructose, and 2-deoxyglucose 4
  • This broader substrate specificity distinguishes it from more selective kinases

Clinical Significance

Understanding hexokinase properties is important in several clinical contexts:

  • Diabetes management: The different kinetic properties of hexokinase versus glucokinase help explain tissue-specific responses to glucose
  • Cancer metabolism: Many cancer cells show upregulation of hexokinase activity as part of the Warburg effect
  • Rare genetic disorders: Deficiencies in hexokinase can lead to hemolytic anemia due to its importance in red blood cell metabolism 1

The low Km value of hexokinase ensures that tissues with high energy demands can efficiently utilize glucose even when blood glucose levels are relatively low, making it a crucial enzyme for maintaining cellular energy homeostasis.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Glucose Testing and Management in Diabetic Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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