The regulation of renal ammoniagenesis in the rat by extracellular factors. III. Effects of various fuels on in vitro ammoniagenesis

Abstract

The addition of many oxidizable substrates to the medium of incubating rat renal slices decreases ammoniagenesis from glutamine and glutamate. Interestingly, lactate and beta-hydroxybutyrate depress ammoniagenesis less in renal slices from acidotic rats compared with normal-control rats. In this study, the effects of an expanded panel of substrates on ammoniagenesis in kidney slices from control and acidotic rats were followed to discern patterns of inhibition. In addition to lactate and beta-hydroxybutyrate, acetate, pyruvate, and perhaps acetoacetate caused relatively less depression of ammoniagenesis in acidotic slices. Citrate, succinate, fumarate, octanoate, and alpha-ketoglutarate decreased ammoniagenesis to the same extent or more in acidotic slices compared with that in normal-control slices. Glycerol had little effect on ammoniagenesis under either condition. From the substrates tested, it can be generalized that those outside the TCA cycle (with exception of octanoate) depress ammoniagenesis less during acidosis, while those in the TCA cycle depress ammoniagenesis equally or even more during acidosis. We hypothesize from the pattern of our results that changes in renal intermediary metabolism at or before citrate formation occur during acidosis and are important regulatory mechanisms for ammoniagenesis.