Abstract
A non-radioactive 2-deoxyglucose (2DG) analog has been developed here for hyperpolarized magnetic resonance investigations. The analog, [13C6,D8]2DG, showed 13% polarization in solution (27,000-fold signal enhancement at the C1 site), following a dissolution-DNP hyperpolarization process. The phosphorylation of this analog by yeast hexokinase (yHK) was monitored in real-time with a temporal resolution of 1 s. We show that yHK selectively utilizes the β anomer of the 2DG analog, thus revealing a surprising anomeric specificity of this reaction. Such anomeric selectivity was not observed for the reaction of yHK or bacterial glucokinase with a hyperpolarized glucose analog. yHK is highly similar to the human HK-2, which is overexpressed in malignancy. Thus, the current finding may shed a new light on a fundamental enzyme activity which is utilized in the most widespread molecular imaging technology for cancer detection – positron-emission tomography with 18F-2DG.
Highlights
A non-radioactive 2-deoxyglucose (2DG) analog has been developed here for hyperpolarized magnetic resonance investigations
HK-4 is important in glucose sensing in the pancreas and in the liver[6] while HK-1 and HK-2 mainly function in other tissues such as muscle and brain
Using a comprehensive kinetic analysis and decomposition of the complex and overlapping [13C6,D8]2DG and [13C6,D8]2DG6P signals we found a differential activity of the yeast hexokinase (yHK) on the α and β anomers of [13C6,D8]2DG as opposed to a non-differential activity on [13C6,D7]glucose anomers
Summary
A non-radioactive 2-deoxyglucose (2DG) analog has been developed here for hyperpolarized magnetic resonance investigations. The analog, [13C6,D8]2DG, showed 13% polarization in solution (27,000fold signal enhancement at the C1 site), following a dissolution-DNP hyperpolarization process. The phosphorylation of this analog by yeast hexokinase (yHK) was monitored in real-time with a temporal resolution of 1 s. It was previously suggested that the increased HK-2 activity forms the basis for the utility of FDG-PET imaging of malignant tumors[5]. In 13C-NMR, as opposed to PET, the chemical evolution of 2DG to 2DG-6-phosphate (2DG6P) can be discerned This property could be useful for differentiating the effects of glucose transporters expression from those of HK expression in vivo. (one with bGK and one without an enzyme), and one measurement was conducted at room temperature (without an enzyme)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
