DRUG-METABOLISM IN ISOLATED PROXIMAL TUBULE CELLS - ALDEHYDE DEHYDROGENASE
- 1 January 1983
- journal article
- research article
- Vol. 224 (3), 699-706
Abstract
The mammalian kidney is composed of numerous cell populations associated with the interstitial spaces, vasculature and various portions of the nephron. Mammalian kidneys exhibit an array of drug metabolizing activities, including the pyridine nucleotide-linked aldehyde dehydrogenase(s) (ALDH). To define the ALDH activity in segment 2 of the proximal tubule, a portion of the nephron which frequently shows drug-induced pathology, proximal tubules were isolated by purely mechanical methods from female rabbits. Isopycnic centrifugation of tubule-derived postnuclear supernates in linear sucrose gradients resulted in propionaldehyde (5 mM)-driven ALDH activity being distributed in a manner consistent with both a mitochondrial and cytosolic localization. Mitochondrial and cystosolic fractions yielded biphasic reciprocal plots when propionaldehyde was used as substrate. Km values of 282 .mu.M and 4 mM were obtained from the mitochondrial enzymes, whereas the cytosolic enzymes gave Km of 132 .mu.M and 2.4 mM. The apparent Vmax values (nmol of NADH produced/min per mg of protein) are 16.3 and 37.8 for the mitochondrial enzymes and 23.5 and 19.0 for the cytosolic enzymes. The S2 proximal tubule cells contain ALDH activities at levels and subcellular sites comparable to those found in the liver. Because the proximal tubules constitute approximately 40% of the renal cortical mass, the high levels of ALDH activity observed in these cells may protect other cortical cells and more distal nephron components by detoxifying potentially cytotoxic aldehydes.This publication has 21 references indexed in Scilit:
- The oxidation of acetaldehyde by isolated mitochondria from various organs of the rat and hepatocellular carcinomaArchives of Biochemistry and Biophysics, 1977
- Intracellular Localization and Characterization of Beef Liver Aldehyde Dehydrogenase IsozymesAgricultural and Biological Chemistry, 1976
- Localization and characteristics of rat liver mitochondrial aldehyde dehydrogenasesArchives of Biochemistry and Biophysics, 1976
- THE LARGE-SCALE SEPARATION OF PEROXISOMES, MITOCHONDRIA, AND LYSOSOMES FROM THE LIVERS OF RATS INJECTED WITH TRITON WR-1339The Journal of cell biology, 1968
- Tissue and subcellular distribution of mammalian aldehyde-oxidizing capacityBiochemical Pharmacology, 1966
- Steroid-sensitive Aldehyde Dehydrogenase from Rabbit LiverJournal of Biological Chemistry, 1961
- IMPROVEMENTS IN EPOXY RESIN EMBEDDING METHODSThe Journal of cell biology, 1961
- SIDE CHAIN OXIDATION OF ALKYL SUBSTITUTED RING COMPOUNDS .1. ENZYMATIC OXIDATION OF PARA-NITROTOLUENE1959
- OXIDATION OF ALDEHYDES BY MITOCHONDRIA OF RAT TISSUESJournal of Biological Chemistry, 1953
- A STUDY OF FIXATION FOR ELECTRON MICROSCOPYThe Journal of Experimental Medicine, 1952