Detection of Pentose Phosphate Pathway Flux Using Hyperpolarized [1-13C]Gluconolactone in Mouse Livers

Karlos X. Moreno¹, Crystal E. Harrison¹, Matthew E. Merritt¹, Zoltan Kovacs¹, Zengdun Shi², Don C. Rockey², A Dean Sherry¹, Craig R. Malloy^1,2

Pentose phosphate pathway flux was studied using hyperpolarized δ-[1-¹³C]gluconolactone injected into an isolated perfused mouse liver. Control livers produced a significant amount of H¹³CO₃^-, a product indicative of pentose phosphate pathway flux and [1-¹³C]gluconate. Hydrogen peroxide damaged livers also produced H¹³CO₃^- and [1-¹³C]gluconate, though the bicarbonate was at lower amounts than the control. CCl₄ treated livers did not produce any observable H¹³CO₃^-, but [1-¹³C]gluconate was produced. These studies show that the lactone is incorporated within the hepatocyte, phosphorylated and metabolized through the pentose phosphate pathway.