This project is a continuation of an investigation into the regulation of intermediary metabolism in the kidney by acid-base changes and the relationship of such regulation to physiologic processes involved in acid-base homeostasis. In previous studies we have related two physiologic processes, the acute increase in citrate clearance in metabolic alkalosis and the chronic increase in NH4 plus excretion and glutamine utilization in metabolic acidosis, to acute and chronic effects of acid-base changes Gn citrate and glutamine metabolism by tissue slices and mitochondria from renal cortex. In the present project we will extend studies by attempting to define the nature of the biochemical changes which result in increased substrate utilization by mitochondria from chronically acidotic dogs. Also we will continue to investigate the mechanism by which changes in pH and bicarbonate concentration regulate mitochondrial metabolism. Special emphasis will be given to evaluation of the role of acid-base changes in regulating mitochondrial substrate transport.