Endocrinology, Vol 112, 393-395, Copyright © 1983 by Endocrine Society

ARTICLES

Identification of an ATP-activated endopeptidase from rat kidney which catalyzes cleavage of parathyroid hormone to fragments identical to those produced in the rat kidney in vivo

RE Botti Jr and JE Zull

An endopeptidase catalyzing cleavage of parathyroid hormone to specific C-terminal and N-terminal fragments was identified in a partially purified membrane fraction from rat kidney. Fractionation on sucrose gradient showed that this activity is present primarily in a light membrane fraction rather than in the basal-lateral membranes, or in the classic lysosomal fraction. The endopeptidase can be extracted from the membranes by freezing and thawing, it has an acid pH optimum, and it catalyzes production of specific fragments of PTH. The major C-terminal fragment produced has its N-terminus at residue 39 of the native hormone. This fragment is identical to the primary PTH fragment found in kidney tissue following injection of iodinated PTH into the systemic circulation of rats (D'Amour et al., 1979). Finally, the cleavage of PTH by this acid endopeptidase is activated by physiological concentration of ATP (10(-4) - 10(-3)M). These results suggest that this enzyme may be involved in PTH catabolism by the kidney, that it may be located in a specialized cell fraction and that hormone catabolism may be regulated by the energy status of the cell.