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MCAT

Unit 2: Lesson 1

Foundation 1: Biomolecules

Cancer and hexokinase

Problem

A key component of many cancers, especially the most aggressive, is their ability to metabolize glucose at a highly elevated rate. The first step in the metabolism of glucose is its phosphorylation to form glucose 6-phosphate, which traps the molecule within the cell. This reaction is unable to proceed in vitro unless the protein hexokinase (HK) and magnesium cations are present; [HK] and [Mg2+] remain constant throughout the reaction.
Different forms of HK (I, II, III, and IV) are found in differing levels throughout the body. Each form displays unique functional characteristics.
Figure 1: Saturation Curves for HK I and IV
Figure 2: In Vitro Kinetic Parameters for HK I, II, and IIIa
Km for glucose (mmol/L)Km for ATP (mmol/L)
Hexokinase I0.030.5
Hexokinase II0.30.7
Hexokinase III0.0031.0
aValues shown are representative of scientific literature; values for HK IV are not normally reported.
Tumors can be located using positron emission tomography (PET) to assay HK activity levels. 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) is a radiolabeled form of glucose that can be taken up normally by all cells and phosphorylated by HK. The 18F isotope undergoes positron emission, allowing it to be detected by PET scans. Since 18F isotope replaces the 2’-OH group, it also prevents further metabolism of the molecule. After the intravenous administration of 18F-FDG, a whole body PET scan is carried out to measure radioactivity levels in various tissues of the body.
What can Mg2+ be considered in the hexokinase reaction?
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