THE EXCRETION OF l-MALIC ACID IN RELATION TO THE TRICARBOXYLIC ACID CYCLE IN THE KIDNEY*

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Abstract
The mechanism of excretion of malic acid was studied in the dog during infusion of several tricarboxylic acid cycle intermediates including l-malic acid itself. With infusion of citrate, [alpha]-ketoglutarate and succinate there was glomerular filtration and net tubular secretion of malate. With each of these substrates following infusion of the suc-cinoxidase inhibitor, malonic acid, the net tubular secretion of malate completely disappeared and glomerular filtration with net reabsorption of malate was seen instead. Thus it appears that the tubules are capable of synthesizing malate from precursors in the tricarboxylic acid cycle and secreting it into the tubular urine. In contrast to these findings, the infusion of fumarate or 1-malate leads only to malate filtration and reabsorption. Thus the tubules are capable of both secretion and reabsorption of malate under certain definite conditions. During l-malate infusion there was a definite "Tm" for malate reabsorption that averaged 4 to 8 mg/minute. During fumarate infusion the capacity of the tubules to reabsorb malate was greatly increased. This phenomenon was shown to be the result of a "catalytic" effect of fumarate on malate reabsorption. The relation of these studies to the operation of the tricarboxylic acid cycle in the kidney and the whole problem of organic acid excretion was discussed.