Uptake, Metabolism and Excretion of Orally and Intravenously Administered, Double‐Labeled N‐GIycoloylneuraminic Acid and Single‐Labeled 2‐Deoxy‐2,3–dehydro‐N‐acetylneuraminic Acid in Mouse and Rat

Abstract

N‐Glycoloyl‐d‐[2‐14C,9‐3H]neuraminic acid enzymically prepared from sodium [2‐14C]pyruvate and N‐glycoloyl‐d‐[6‐3H]mannosamine by N‐acetylneuraminate lyase in 52% yield was orally administered to 20‐day‐old fasted mice. In the course of 6 h 98% of the total radioactivity belonging to the originally administered N‐glycoloyl‐neuraminic acid was resorbed from the intestine and appeared in the urine. 6 h after application total 0.7% of the 3H and 0.5% of the 14C radioactivity were recovered in blood, liver, spleen, kidney and brain. The difference between the 14C and the 3H quantities was detected as exhaled 14CO2. After intravenous injection of N‐glycoloylneuraminic acid into rats, 90% of the radioactivity was excreted in the urine within 10 min corresponding to the originally applied substance. After 6 h, 1.3% of the 3H and 1% of the 14C radioactivity were left in blood and in liver, spleen, kidney and brain. An efficient preparation of 2‐deoxy‐2,3‐dehydro‐N‐acetylneuraminic acid and 2‐deoxy‐2,3‐dehydroneuraminic acid from N‐acetylneuraminic acid is described, as well as the synthesis of a tritium‐labelled 2‐deoxy‐2,3‐dehydro‐N‐acetylneuraminic acid. The unsaturated neuraminic acid derivative behaved similarly to N‐glycoloylneuraminic acid after oral and intravenous application. 99% of the radioactivity orally administered was resorbed from the intestine and excreted in the urine without chemical alteration in the course of 6 h. About 1% of the radioactivity administered orally to mice and 1.7% of the same compound administered intravenously to rats were still found in blood, liver, spleen, kidney and brain after this time. The results suggest that the small amount of N‐glycoloylneuraminic acid retained in the organism was at least partially cleaved by N‐acetylneuraminate lyase. The high excretion rate of unchanged 2‐deoxy‐2,3‐dehydro‐N‐acetylneuraminic acid and the fact that it does not act as a substrate for the lyase supposes that there is no further metabolism of this sialic acid under the conditions described. It may be concluded from these observations that N‐glycoloylneuraminic acid occurring in food cannot be used directly for the biosynthesis of glycoconjugates, which is important from an immunological point of view. The results presented here are compared with those obtained after application of double‐labeled N‐acetylneuraminic acid in former studies [U. Nöhle and R. Schauer (1981) Hoppe‐Seyler's Z. Physiol. Chem. 362, 1495–1506]. Copyright © 1982, Wiley Blackwell. All rights reserved