Oxidation of 2-deoxyglucose by human polymorphonuclear leukocytes

Area of Science:

• Immunology
• Cellular Metabolism

Background:

• Human polymorphonuclear leukocytes (PMNLs) play a critical role in immune responses.
• Understanding PMNL metabolic pathways is essential for comprehending their function and dysfunction.

Purpose of the Study:

• To investigate the metabolic fate of 2-deoxyglucose in human PMNLs.
• To determine the pathways involved in 2-deoxyglucose metabolism and its regulation by stimuli.

Main Methods:

• Utilized radiolabeled [1-14C]2-deoxyglucose to trace metabolic activity in human PMNLs.
• Stimulated PMNLs with phorbol myristate acetate (PMA) and opsonized zymosan.
• Assessed 2-deoxyglucose oxidation and transport in normal and defective PMNLs (chronic granulomatous disease).

Main Results:

• PMNLs metabolize 2-deoxyglucose to 14CO2 upon stimulation with PMA or zymosan.
• 2-deoxyglucose oxidation is less efficient than glucose oxidation but occurs in normal PMNLs, not in chronic granulomatous disease cells.
• PMA-induced oxidation does not fully explain transport inhibition, and zymosan-induced transport increase does not significantly boost oxidation.

Conclusions:

• 2-deoxyglucose metabolism in PMNLs is primarily mediated by the hexose monophosphate shunt.
• This pathway's activity with 2-deoxyglucose is intermediate compared to glucose.
• Enzymes of the hexose monophosphate shunt show reduced efficiency with 2-deoxyglucose derivatives.