Valine oxidation in the rat medullary thick ascending limb

In the kidney, a branched-chain amino acid transferase (BCAAT) activity has been localized mainly in the medullary thick ascending limb (MTAL) of the rat nephron. BCAAT is the first enzyme involved in the metabolic pathway of the three branched-chain amino acids (BCAA): leucine, isoleucine and valine. The present work has been designed to study valine catabolism. Valine and leucine oxidation in MTAL were compared by measuring the rate of 14CO2 produced when these substrates were incubated as sole substrates at a final concentration of 1 mM. Since glucose is also metabolized in MTAL, valine and leucine oxidation were quantified also in the presence of glucose (1 mM). The results show that: (1) valine oxidation was greater than that of leucine (63.0 +/- 4.7 vs 39.7 +/- 5.2 pmol.h-1 x micrograms-1 protein, respectively; P < 0.001). As previously shown, leucine oxidation was found to be increased in the presence of glucose whereas glucose oxidation decreased. In contrast, the presence of glucose strongly diminished valine oxidation (19.2 +/- 1.9 vs 63.1 +/- 4.7 pmol.h-1 x micrograms-1 protein; P < 0.001) whereas glucose oxidation was increased in the presence of valine (268.2 +/- 14.9 vs 229.6 +/- 16.2 pmol.h-1 x micrograms-1 protein; P < 0.05). We conclude that in rat MTAL, under near physiological conditions (in the presence of glucose, as in vivo), leucine is a preferential respiratory fuel as compared to valine. However, valine supports energetic salt transport and facilitates glucose oxidation.