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Biomedical subjects

A Lundblad

Publications and source records attributed to A Lundblad.

At least 91 records · Page 5Linked to original sources

Urinary amino acid glycosides and oligosaccharides in health and disease.

Due to heterogeneity and lack of suitable fractionation techniques it is only recently that more detailed information about urinary low molecular weight carbohydrates has been obtained. Ingemar Berggård was one of the pioneers who opened up this field and outlined the directions towards fruitful progress. Today more than one hundred well characterized oligosaccharides and amino acid glycosides have been described. This review covers the latest development and discusses the mechanisms behind the urinary excretion.

Blood Group Antigens↗

Increased urinary excretion of free N-acetylneuraminic acid in thirteen patients with Salla disease.

Thirteen severely retarded patients with Salla disease, a new type of lysosomal storage disorder, have been studied biochemically. All patients excreted approximately ten times more free sialic acid than normal individuals. The isolated sialic acid was characterized by paper chromatography, thin-layer chromatography, optical rotation, 13C and 1H nuclear magnetic resonance spectroscopy, and mass spectrometry of its permethylated derivative. The results clearly indicated that the excreted sialic acid was identical to N-acetylneuraminic acid. The main sialylated trisaccharide present in the urine of the patients was identified as 3'-sialyllactose by sugar and methylation analysis. The excreted amounts were found to be within normal range.

Carbohydrate Metabolism, Inborn Errors↗

Urinary excretion of oligosaccharides induced by galactose given orally or intravenously.

The effect of oral administration of galactose, lactose, and sucrose and intravenous injection of galactose on the urinary excretion of blood-group-active oligosaccharides has been studied. Galactose given either as the free sugar, a glycoside (lactose) or a constituent of normal diet was an absolute requirement for the formation and excretion of A-trisaccharide, B-trisaccharide and 2'-fucosylgalactose in blood group A, B and O(H) secretors, respectively. Great individual variation was seen in the amounts of galactose-dependent oligosaccharides excreted. Injection of galactose resulted in excretion of 3-59% of the amount of oligosaccharide formed after oral administration to the same individual. The mean ratio A-trisaccharide/B-trisaccharide was 2.7 in four blood-group-A1B secretors and 0.22 in three A2B secretors and can thus serve as a parameter for chemical differentiation between the two blood groups. The excretion of larger blood-group-active oligosaccharides, including the A-pentasaccharide, the B-pentasaccharide and lactodifucotetraose, that are normal components in urine from, respectively, starved A, B, and H secretors, was about the same after oral administration of galactose or lactose. The B-trisaccharide was the only oligosaccharide detected in plasma after oral galactose administration to a blood-group-B secretor individual. The concentration was 0.38 mg/l of plasma.

ABO Blood-Group System↗

Determination of Leb-active oligosaccharides in urine of pregnant and lactating women by radioimmunoassay.

Antiserum obtained by immunizing a goat with lacto-N-difucohexaose I, a Leb blood-group hapten, coupled to poly-L-lysine was used in a radioimmunoassay to detect Leb-active oligosaccharides (chiefly lacto-N-difucohexaose I) in urine of 138 pregnant and lactating women of different ABO and Lewis blood groups. Specificity of the method was determined by comparing inhibitory activities of 18 oligosaccharides. Only women who belonged to the Leb blood group excreted Leb-active oligosaccharides in urine. Leb-active oligosaccharides increase during pregnancy, reaching levels up to approximately 70 mumol lacto-N-difucohexaose I equivalents per pmol creatinine in the third trimester and early post-partum period. Excretion varies considerably but tends to be highest in those individuals who strongly express the Leb antigen on their red blood cells or who belong to blood group O. Leb-active oligosaccharides were detected in plasma of a few individuals but at concentrations 1000-fold lower than in urine.

ABO Blood-Group System↗

Glucose-containing oligosaccharides in the urine of patients with glycogen storage disease type II and type III.

Patients with glycogen storage disease type II and type III were recently found to excrete increased amounts of a glucose-containing tetrasaccharide DGlcp(alpha1 leads to 6)DGlcp(alpha1 leads to 4)DGlcp(alpha1 leads to 4)DGlc [Lennartson, G., Lundblad, A., Sjöblad, S., Svensson, S. and Ockerman, P.A. (1976) Biomed. Mass Spectrom. 3, 51--54]. In addition to this tetrasaccharide, urine from these patients also contains larger oligosaccharides containing only glucose. From urine of patients with glycogen storage disease type II and type III, three and four oligosaccharides respectively have been isolated. Structural studies including sugar analyses, methylation analyses, partial acid hydrolysis and optical rotation revealed that three compounds were present in the urine of both patients. Their proposed structures or partial structures are as follows: DGlcp(alpha1--6)DGlcp(alpha1--6)DGlcp(alpha1--4)DGlcp(alpha1--4)DGlcp(alpha1--4)DGlc, DGlcp(alpha1--4)DGlcp(alpha1--6)DGlcp(alpha1--6)DGlcp(alpha1--4)DGlcp(alpha1--4)DGlc, and DGlcp(alpha1--6)DGlcp(alpha1--4)DGlcp(alpha1--4)DGlcp(alpha1--4)DGlcp(alpha1--6)DGlcp(alpha1--4)DGlcp(alpha1--4)DGlc. A fourth compound has been partially characterized as a branched heptasaccharide with four (1 leads to 4) linkages and two (1 lead to 6) linkages. Glycogen is possibly the origin of these compounds. However, the number of (1 leads to 6) linkages is higher than expected and may indicate a shorter distance between branches in glycogen than has been generally assumed.

Child↗

Urinary abnormalities in fucosidosis. Characterization of a disaccharide and two glycoasparagines.

The urinary excretion of fucose-containing material was found to be highly increased in a patient with fucosidosis type 2. Three structurally related compounds, a disaccharide and two glycoasparagines, were isolated from the urine. The isolation procedure included ultrafiltration, gel chromatography on Sephadex G-25, preparative zone electrophoresis and paper chromatography. From structural studies including optical rotation, sugar analysis, methylation analysis, ninhydrin degradation, reduction with lithium aluminium hydride and partial hydrolysis, the following structures were deduced: formula (see text), where Fucp is fucopyranose, Manp is mannopyranose, Galcp is galactopyranose, GlcNAcp is 2-acetamido-2-deoxyglucopyranose and Asn is asparagine. The yields of these compounds were 1.7, 40, and 6 mg/l, respectively. The origin of the disaccharide and the two glycoasparagines is probably the core region of glycoprotein carbohydrate chains.

Asparagine↗

Biosynthesis of the blood-group-B-specific trisaccharide in a rhesus monkey.

A Rhesus monkey, serologically grouped as B, has been shown to excrete low-molecular-weight carbohydrate material in urine closely related to that found in human urine. Galactose feeding resulted in the excretion of a trisaccharide which was shown to be identical to the trisaccharide isolated from the urine of group B humans under the same conditions. Experiments in which [14C]galactose was administered both orally and via an intestinal vein demonstrated that the intestine is the site of biosynthesis.

ABO Blood-Group System↗

Structural analysis of nine oligosaccharides isolated from the urine of a blood group O, nonsecretor, woman during pregnancy and lactation.

Nine oligosaccharides have been isolated from urine collected from an O(H), Le(a+ b-), nonsecretor, woman during her pregnancy and subsequent lactation. One of them is a new hexasaccharide denoted lacto-N-neo-difucohexaose II: beta-D-Gal-(1 leads to 4)-[alpha-L-Fuc-(1 leads to 3)]-beta-D-GlcNAc-(1 leads to 3)-beta-D-Gal-(1 leads to 4)-[alpha-L-Fuc-(1 leads to 3)]-D-Glc. Seven of the remainder were identified as the milk oligosaccharides lacto-N-difucohexaose II, lacto-N-fucopentaose II and III, lacto-N-tetraose, 6'-galactosyllactose, 3-fucosyllactose, and lactose. The ninth component is a glucose-containing tetrasaccharide, alpha-D-Glc-(1 leads to 6)-alpha-D-Glc-(1 leads to 4)-alpha-D-Glc-(1 leads to 4)-D-Glc, previously found in normal human urine. The oligosaccharides were isolated by gel chromatography, preparative zone electrophoresis, and paper chromatography. The structures were determined by sugar and methylation analyses. Sequence analysis of tri- and tetra-saccharides was carried out by gas-liquid chromatography-mass spectrometry of reduced and permethylated oligosaccharide derivatives. The monosaccharide sequence in penta- and hexasaccharides was deduced from gas chromatographic-mass spectrometric studies of di- and trisaccharides obtained from partial acid hydrolysis of the parent compound. Anomeric configurations were deduced from the optical rotation.

ABO Blood-Group System↗

Structural analysis of oligosaccharides isolated from the urine of a blood group A, secretor, woman during pregnancy and lactation.

Twenty different oligosaccharides have been isolated from urine collected from an A, Le(a- b+), secretor woman during her pregnancy and subsequent lactation. Nine of these have been found previously in the milk of Le (a- b+) individuals. Three new fucose-containing oligosaccharides denoted lacto-N-neotrifucoheptaose II (alpha-L-Fuc-(1 leads to 2)-beta-D-Gal-(1 leads to 4)-[alpha-L-Fuc-(1 leads to 3)]-beta-D-GlcNAc-(1 leads to 3)-[alpha-L-Fuc-(1 leads to 2)]-beta-D-Gal-(1 leads to 4)-D-Glc), lacto-N-neodfucohexaose I (alpha-L-Fuc-(1 leads to 2)-beta-D-Gal-(1 leads to 4)-[alpha-L-Fuc-(1 leads to 3)]beta-D-GlcNAc-(1 leads to 3)-beta-D-Gal-(1 leads to 4)-D-Glc), and lacto-N-difucohexaose IV (alpha-L-Fuc-(1 leads to 2)-beta-D-Gal-(1 leads to 3)-beta-D-GlcNAc-(1 leads to 3)-[alpha-L-Fuc-(1 leads to 2)]-beta-D-Gal-(1 leads to 4)-D-Glc) are described. Three new myo-inositol-containing oligosaccharides which are characteristic for pregnancy have also been isolated. Their structures are: alpha-D-GalNAc-(1 leads to 3)-[alpha-L-Fuc-(1 leads to 2)]-beta-D-Gal-(1 leads to 0)-[alpha-L-Fuc-(1 leads to 0)]-myo-inositol; alpha-L-Fuc-(1 leads to 2)-beta-D-Gal-(1 leads to 0)-[alpha-D-Fuc-(1 leads to 0)]myo-inositol; and alpha-L-Fuc-(1 leads to 2)-beta-D-Gal-(1 leads to 0)-myo-inositol, respectively. Three oligosaccharides containing only glucose were found and partially characterized. In addition, two oligosaccharides described previously (a glucose tetrasaccharide (Hallgren, P., Hansson, G., Henriksson, K.-G., Häger, A., Lundblad, A., and Svensson, S. (1974) Eur. j. clin. Invest. 4, 429-433) and a urine A pentasaccharide (Lundblad, A., and Svensson, S. (1973) Carbohyd. Res. 30, 187-189) were also isolated and characterized. The isolation procedure included ultrafiltration, gel chromatography on Sephadex G-25, and preparative paper chromatography, Structural determination involved sugar and methylation analyses. Tri- and tetrasaccharides were investigated by combined gas-liquid chromatography-mass spectrometry. Sequence analyses of larger oligosaccharides were performed by combined gas-liquid chromatography-mass spectrometry of di- and trisaccharides obtained after partial acid hydrolysis of the parent compound. Anomeric configurations were deduced from optical rotations and by comparison with authentic samples.

ABO Blood-Group System↗

Quantitation of some urinary oligosaccharides during pregnancy and lactation.

The excretion rates of different oligosaccharides in the urine of two individuals, a blood group O, nonsecretor woman, and a blood group A, secretor woman, were studied at different times during pregnancy and lactation. Quantitative determinations of di-, tri-, and tetrasaccharides were performed by combined gas-liquid chromatography-mass spectrometry. Larger oligosaccharides were quantitated by their content of total hexose or 6-deoxyhexose (fucose). The urinary oligosaccharide excretion during pregnancy is detectable by the 13th week. All oligosaccharides studied increased and reached the highest levels during the last trimester. During lactation more complex excretion patterns were observed. Lactose and oligosaccharides with a lactose backbone were the most predominant compounds. Oligosaccharides with a lacto-K-tetraose or a lacto-N-neotetraose backbone were present both during pregnancy and lactation, but the former type showed a much more pronounced increase of excretion during lactation. Four oligosaccharides containing only D-glucose were found in largest amounts during pregnancy. One of these oligosaccharides, a glucose tetrasaccharide, was quantitatively determined in the urine of 13 individuals and the excretion was found to decrease 2- to 5-fold in the first week post partum relative to the last week of pregnancy. Urine from a woman whose fetus died unexpectedly in the 24th week of pregnancy was also studied. No oligosaccharides characteristic of a normal pregnancy could be detected, suggesting that at least some oligosaccharides appearing specifically during pregnancy might reflect the function of the placenta or the fetus, or both.

ABO Blood-Group System↗

Structural determination of three glycoasparagines isolated from the urine of a patient with aspartylglycosaminuria.

Three different glycoasparagines have been isolated from the urine of a patient with aspartylglycosaminuria and their structures determined using sugar, amino acid and methylation analysis, enzymic degradation and measurements of the optical rotations. The structures were 2-acetamido-1-N-(4'-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine (yield 135 mg/l) beta-D-galactopyranosyl-(1 leads to 4)-2-acetamido-1-N-(4'-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine (yield 35 mg/l), and alpha-D-mannopyranosyl-(1 leads to 6)-beta-D-mannopyranosyl-(1 leads to 4)-2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1 leads to 4)-2-acetamido-1-N-(4'-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine (yield 30 mg/l). The first two compounds have previously been described, whereas the third compound is different from any of the glycoasparagines isolated before.

Acetylglucosamine↗