Studies on the metabolism of hydroxypyruvate in animal tissues

Abstract

The metabolism of specifically C14-labeled hydroxypyruvate, and particularly its conversion into glucose, was studied in the intact rat and in rat-liver slices. In the fasting rat, radioactivity of subcutaneously injected hydroxy-3-C14-pyruvate and hydroxy-2-C14-pyruvate appears in the liver glycogen. This incorporation amounted to 1.9-5.0% of the dose given, whereas with l-C14-glucose under similar conditions incorporation was 3.8%. Stepwise degradation of the glucose obtained on hydrolysis of the liver glycogen showed that with either hydroxy-3-C14 or hydroxy-2-C14-pyruvate a nearly symmetrical pattern of distribution occurred. With the former, main labeling was in C-l and C-6 of glucose; with the latter, it was in C-2 and C-5. Randomization of radioactivity to the adjacent end carbons (C-l C-2 and C-6 C-5) was observed, but it was much less than has been reported for similarly labeled lactate or pyruvate, though with hydroxy-3-C14-pyruvate it was almost identical with that reported for DL-3-C14-serine. When incubated aerobically in Krebs-Ringer bicarbonate solution with liver slices (from fed rats). 95% of specifically labeled hydroxypyruvate is metabolized. The utilization of substrate and incorporation of radioactivity into glucose were much higher with hydroxy-3-C14-pyruvate (average 15.7% of total radioactivity incorporated) than with L-3-C14 -serine (average 1.6%), the latter percentage being similar to that reported for either L- or D-3-C14-serine by Elwyn et al. (1957). In similar experiments with hydroxy-1-C14-pyruvate incorporation was almost exclusively in C-3 and C-4 of glucose and amounted to 12% of the total C14; parallel experiments with NaHC14O3 showed relatively slight incorporation into glucose. These experiments are considered to show that the rat in vivo aNd rat-liver tissue in vitro are able to incorporate readily all 3 carbon atoms of hydroxypyruvate into the glucose molecule, the evidence suggesting that this occurs symmetrically with combination of two unbroken C3 chains by a fairly direct route not passing through L-serine and probably not through pyruvate as intermediates. The possible bearing of these observations on serine metabolism is discussed.