Interdependence of O2 consumption, renal NEFA pattern and N-acetylation of PAH in the isolated perfused rat kidney. Effect of long-chain NEFA and of PGF2 alpha on the renal N-acetyltransferase activity.

Tissue concentration of nonesterified fatty acids (NEFA) exerting an inhibitory effect on renal N-acetyltransferase activity was determined in the isolated perfused rat kidney. Concurrently, O2 consumption and the N-acetylation rate of p-aminohippurate (PAH) were measured. In a second series of experiments, the mode of inhibition of NEFA on acetylating enzyme(s) was studied. Amount and pattern of NEFA as well as N-acetylation rate of PAH in the kidney were related to the O2 consumption: lower O2 supply corresponded to a higher tissue NEFA concentration as well as lower N-acetylation rate, increased O2 supply resulted in a low tissue NEFA concentration and an increased N-acetylation rate of PAH. Decreasing O2 supply elevated the tissue concentration of linoleate especially. NEFA with a carbon chain length of C16-C20 inhibited renal N-acetyltransferase activity in vitro competitively according to the sequence C16, C18, C18:1, C18:2, C18:3 = C20. It is inferred that hypoxia interferes with the N-acetylation of PAH in the rat kidney by increasing the content and changing the pattern of fatty acids, thereby inhibiting the N-acetylating enzyme(s).

Investigations on the functional role of rat liver carboxylesterase isoenzymes.

We have compared the substrate specificities of two isoenzymes of rat liver esterase. Isoenzyme E1 which we isolated earlier, and isoenzyme EA, the isolation of which is reported here, have very similar molecular weights, subunit weights, and isoelectric points. In contrast, the two enzymes have distinctly different substrate optima when tested with a series of esterase substrates. Our finding poses the question, as to whether the rather unspecific in vivo behaviour of liver carboxylesterase could be explained by an ensemble of isoenzymes with overlapping substrate specificitites and mutually complementary substrate optima. The biological function of esterase isoenzymes appears to represent an extension of the range of hydrolytic competence of a single enzyme.