Substrate support of medullary thick ascending limb oxygen consumption.

The oxygen consumption of medullary thick ascending limb tubule suspensions was measured in the presence and absence of exogenous glucose. In the absence of exogenous glucose, the control oxygen consumption decreased 15%. Under identical conditions, the nystatin-stimulated oxygen consumption was inhibited 36%, indicating that oxidation of endogenous substrates could not meet the ATP demand of the fully stimulated Na+-K+-ATPase. Addition of inhibitors of fatty acid oxidation (bromooctanoate and tetradecylglycidic acid) further inhibited oxygen consumption, revealing that endogenous fats are oxidized in control and nystatin-stimulated states. Inhibition of endogenous carbohydrate (2-deoxy-D-glucose present) or amino acid (aminooxyacetate present) oxidation suppressed the nystatin response. In the presence of 10 mM glucose, only aminooxyacetate inhibited the nystatin-stimulated oxygen consumption, suggesting that the involvement of the malate-aspartate shuttle in redox balance during increased glycolytic flux. Addition of fatty acids or acetoacetate increased the control, nystatin-stimulated and uncoupler-stimulated oxygen consumption of tubules suspended in 10 mM glucose, indicating that these tubules oxidize exogenous fatty acids and ketones and oxidation of exogenous glucose alone may not meet all the energy demands of the tissue. Conversely, the addition of organic acids failed to enhance control oxygen consumption, possibly due to the absence of transport systems for these compounds in the medullary thick ascending limb tubules.(ABSTRACT TRUNCATED AT 250 WORDS)