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N-Glycoloyl-~-[2-' 4C,9-3H]neuraminic acid enzymically prepared from sodium 12-l 4C]pyruvate and Nglycoloyl-~-[6-~H]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-glycoloylneuraminic 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 I4C radioactivity were recovered in blood, liver, spleen, kidney and brain. The difference between the 14C and the 3H quantities was detected as exhaled 14C02. 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-Nacetylneuraminic 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 Nglycoloylneuraminic 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. Nohle and R. Schauer (1981) HoppeSeyler's 2. Pkysiol. Ckem. 362, 1495 -15061. N-Glycoloylneuraminic acid is found as a terminal sugar in various glycoconjugates and oligosaccharides. Though biosynthesis has already been investigated [I, 21, nothing is known about the metabolism of extracellular free Neu5Gc. We have reported the fate of orally and intravenously administered, double-labeled Neu5Ac in mouse and rat [3]. It was concluded from the observations that the bulk of free Neu5Ac is excreted unchanged in the urine and to a smaller amount cleaved by Nacetylneuraminate lyase suggesting that this sialic acid cannot be directly used for ...

A mixture of-/V-acetyl- [4,5,6,7,8,[9][10][11][12][13][14] C]neuraminosyl-a(2-3(6))-galactosyl-0( 1 -4)-glucose ([ l4 C]sialyl-lactose) and TV-acetylneuraminosyl-a(2-3(6))-galactosyl-|3(l-4)-glucit-l-[ 3 H]ol (sialyl-[ 3 H)lactitol) as well as porcine submandibular gland mucin labeled with TV-acetyland yV-glycoloyl-[9-3 H]neuraminic acid were administered orally to mice. The distribution of the different isotopes was followed in blood, tissues and excretion products of the animals. One half of the [ 14 C]sialyl-lactose/sialyl-[ 3 H]lactitol mixture given orally was excreted unchanged in the urine. The other half was hydrolysed by sialidase and partly metabolized further, followed by the excretion of 30% of the 14 C-radioactivity as free 5,6,7,8,[9][10][11][12][13][14] C]neuraminic acid and 60% of this radioactivity in the form of nonanionic compounds including expired 14 C0 2 within 24 h. The l4 C-radioactivity derived from the [ 14 C]sialyl-lactose/sialyl-[ 3 H]lactitol mixture which remained in the bodies of fasted mice after 24 h was less than 1 %. In the case of well-fed mice, a higher amount of the sialic acid residues was metabolized. The bulk of radioactivity of the mucin was resorbed within 24 h. About 40% of the radioactivity administered was excreted by the urine within 48 h; 30% of this radioactivity represented sialic acid and 70% other anionic and non-anionic metabolic products. 60% of the radioactivity administered remained in the body, and bound 3 H-labeled sialic acids were isolated from liver. Enzymes:jV-Acetylneuraminate lyase, yV-acetylneuraminate pyruvate-lyase (EC 4.1.3.3); Sialidase, acylneuraminyl hydrolase (EC 3.2.1.18). A bbreviations: NeuSAc = yV-Acetyl-D-neuraminic acid; Neu5,9Ac 2 = JV-acetyl-9-0-acetyl-D-neuraminic acid; NeuSGc = yV-glycoloyl-D-neuraminic acid; NeuSAcyl = '-acyl-D-neuraminic acid; NeuSAc-lyase = W-acetylneuraminate lyase; ManNAc = W-acetyl-D-mannosamine; Sialyllactose = Neu5Aca(2-3(6))Gal0(l-4)Glc (mixture of (2-3)-and (2-6)-glycosidically bound NeuSAcJ; sialyllactitol = Neu5Aca(2-3(6))Gal/3(l-4)glucit-l-ol; [ l4 5,6,7,8,[9][10][11][12][13][14] C]Neu5Aca(2-3(6))Gal0(l-4)Glc;( 3 HJsialyl-lactose = [9-3 H]Neu5Aca(2-3(6))Gal/3(l-4)Glc; sialyl-l 3 H]lactitol = Neu5Aa*(2-3(6))Gal0(l-4)glucit-l-| 3 H]ol; [ 14 C]sialyl-lactitol = [4 5,6,7,8,9-14 C]Neu5Aca(2-3(6))Gal0(l-4)glucit-l-ol; [ 3 H]sialyl-lactitol= (9-3 HJNeu5Aca(2-3(6))Gal0(l-4)glucit-l-ol. Copyright © by Walter de Gruyter & Co -Berlin · New York Brought to you by | University of Queensland -UQ Library Authenticated Download Date | 6/24/15 12:27 AM 1458 U. Nöhle and R. Schauer Bd. 365 (l984)Sialyl-a(2-3)-[ 3 H]lactitol was injected intravenous-resorbed. This is followed either by excretion as ly into rats; the substance was rapidly excreted in the urine without decomposition.These studies show that part of the sialic acids bound to oligosaccharides and glycoproteins can be hydrolysed in intestine by sialidase and be free sialic acid or by metabolization at variable degrees, which apparently depends on the compound ...

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2‐Deoxy‐2, 3‐didehydro‐N‐glycoloylneuraminic acid has been found to occur in porcine, bovine and equine submandibular glands as well as in the urine of pig, horse and rat. This novel, unsaturated sialic acid was isolated by gel filtration and ion‐exchange chromatography. Final purification was achieved by column chromatography or by preparative thin‐layer chromatography on cellulose. The structural analysis was performed by combined capillary gas‐liquid chromatography/mass spectrometry. The various data were compared with those from synthetic 2‐deoxy‐2, 3‐didehydro‐N‐acetylated derivative was present in the materials analyzed. The inhibitory effect of 2‐deoxy‐2, 3‐didehydro‐N‐glycoloylneuraminic acid on Vibrio cholerae sialidase using N‐acetylneuraminyl‐(α2→3)‐lactose as substrate is slightly higher (50% inhibition at 10 μM) when compared with 2‐deoxy‐2, 3‐didehydro‐N‐acetylneuraminic acid (50% inhibition at 15 μM).