Metabolic Effects of Hypoxia in Colorectal Cancer by 13C NMR Isotopomer Analysis
Figure 1
[U-13C]glucose as a carbon tracer for monitoring glycolysis and Krebs cycle. Through glycolysis and lactic fermentation [U-13C]lactate is produced which is distinguishable (multiplets in each 13C satellite due to , , and —duplet of triplets since and have similar magnitude) from tissue lactate or lactate originating from unenriched carbon sources. [1,2-13C2]acetil-CoA originating from [U-13C]pyruvate leads to incorporation of 13C atoms in Krebs cycle intermediates and other metabolites that exchange with those (e.g., glutamate). It is possible to follow Krebs cycle kinetics by monitoring the 13C multiplet due to carbon 4 of glutamate. The duplet component (D 45) results from the simple entrance of [1,2-13C2]acetil-CoA but the quartet requires further cycling and combination of [1,2-13C2]acetil-CoA with previously enriched oxaloacetate (OAA). A simple ratio of Q/D 45 is proportional to Krebs cycle flux and denotes higher rates of oxidative metabolism in tissues as opposed to glycolysis. Metabolic fluxes denote the major pathways for [U-13C]glucose use.
