Enzyme kinetics: Forms of hexokinase

The first step in the metabolism of glucose is its phosphorylation to form glucose 6-phosphate. This reaction, which is catalyzed by hexokinase (HK), traps the glucose molecule within the cell. In vitro, the reaction is unable to proceed unless HK and magnesium cations are present. Over the course of the reaction, the concentrations of HK and Mg${}^{2+}$‍ remain constant. Different forms of HK (I, II, III, and IV) are found at different levels throughout the body and each form displays unique functional characteristics. HKII, for instance, is found in the outer mitochondrial membrane, allowing it to interact closely with the voltage-dependent anion channel (VDAC).

The saturation curves for HK I and IV are shown in Figure 1.

Figure 1 Saturation Curves for HK I and IV

Table 1 In Vitro Kinetic Parameters for HK I, II, and III; the Km values for HK IV are not usually reported

Cancer cells - particularly those that are highly aggressive - increase glucose uptake and metabolism by upregulating glucose transporters as well as upregulating certain forms of HK. In addition, the association of HK II with VDAC in cancer cells contributes to the inhibition of apoptosis. The upregulation of certain forms of HK in cancer cells allows tumors to be located using positron emission tomography (PET), which assays HK activity levels. During PET, [18F]fluoro-2-deoxy-D-glucose (18F-FDG), a radiolabeled form of glucose, is injected in the body, 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 the 18F isotope replaces the 2’-OH group, it also prevents further metabolism of glucose. 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.