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Grötsch, Hropot, Klaus, Malerczyk and Mattenheimer: Enzymuria of the rat: Biorhythms and sex differences 343 Summary: Alanine aminopeptidase, -glutamyltransferase and N-acetyl-ß-Z)-glucosaminidase were measured daily over 65 days in 24-hour urine of male and female Wistar rats. The mathematical evaluation was based on the Föw/er-analysis. The excretion of alanine aminopeptidase and -glutamyltransferase was higher in male than in female rats. This sex-dependent difference was not observed for N-acetyl-ß-/)-glucosaminidase. The excretion of the 3 enzymes followed a biorhythm with a dominant period of 7 days forglutamyltransferase and N-acetyl-ß-£>-glucosaminidase and one of 9 days for alanine aminopeptidase. Biorhythms and sex differences of enzymuria should be considered in experimental designs. Enzymurie der Ratte: Biorhythmen und GeschlechtsdifferenzenZusammenfassung: Alaninaminopeptidase, -Glutamyltransferase und N-Acetyl-ß-D-glucosaminidase wurden täglich über 65 Tage bei männlichen und weiblichen Wistar-Ratten im 24 h-Urin gemessen. Die Ergebnisse wurden vermittels fbwr/er-Anälyse ausgewertet. Die Ausscheidung von Alaninaminopeptidase und -Glutamyltransferase zeigte deutliche geschlechtsabhängige Unterschiede, wobei von männlichen Ratten mehr ausgeschieden wurde als von weiblichen Tieren. N-Acetyl-ß-/)-glucosaminidase zeigt diese Unterschiede nicht. Die Ausscheidung der drei Enzyme unterlag Biorhythmen mit Periodenlängen von sieben Tagen für -Glutamyltransferase und N-Acetyl-ß-jp-glucosaminidase und neun Tagen für Alaninaminopeptidase. Biorhythmen und Geschlecht$differenzen in der Enzymurie sind bei Versuchsplanungen zu berücksichtigen. Introduction. , « , , years the rat has been used äs the main experimental Urine enzymes äre being used with increasing animal in enzyine excretion studies. This animal frequency äs sensitive indicatöfs for early detection shows significant enzymuria when substances are of renal damage. Many investigatiöns include a administered which cause increased enzymuria in discussipn of biörhythms in man and animals, re-man. The rat tolerates well single-cage housing in speetively (l -3), A few reports on experimental ani-long term experiments. Enzymes with the smallest mal models document this coherence of biörhythms experimental Variation and good reproducibility are and nephrptoxicity with a close correlation between alanine aminopeptidase, -glutamyltransferase and enzyme excretion and renal damage. Of the large N-acetyl-ß^jD-glucosaminidase. The aim of this study nuinber of urine enzymes, it is mainly those from the was to apply modern mathematical methods to the proximal tübular cells that are of particular interest investigation of biörhythms and sex-specific for toxicological and clinical investigatiöns. In recent differences in the excretion of these enzymes over a

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Ammonia excretion by the kidney has long been known to increase when a constant acid load is given to healthy subjects. This was clearly delineated by Sartorius, Roemmelt, and Pitts (1), who reported that when healthy humans were given a constant amount of ammonium chloride daily, there was a gradual increase in the excretion of ammonia, accompanied by an increased excretion of protons, and by an adaptation that resulted in the conservation of sodium and potassium ions.These experiments were preceded by those of Van Slyke and his co-workers (2), who had demonstrated that glutamine was extracted from the renal arterial blood of acidotic dogs in amounts sufficient to account for about 60% of the NH3 excreted by the kidneys-an observation recently confirmed and extended by the experiments of Pitts and his colleagues (3, 4). The infusion of a variety of amino acids into the acidotic dog has also been shown to increase the rate of excretion of ammonia (54), L-glutamine, L-asparagine, Land D-alanine, and L-histidine being the most effective.The nature of the metabolic pathways involved and the enzymes responsible for catalyzing the relevant reactions are not yet clearly understood.