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).
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