Direct utilization of mannose for mammalian glycoprotein biosynthesis
| Autor: | Gordon Alton, James R. Etchison, Martin Hasilik, K. Panneerselvam, Ralf Niehues, Fariba Fana, Hudson H. Freeze |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Protein glycosylation
Glycosylation Administration Oral Mannose Tritium Biochemistry chemistry.chemical_compound Tumor Cells Cultured Extracellular medicine Animals Glycoproteins Glycoprotein Biosynthesis Mammals chemistry.chemical_classification Mannose-6-Phosphate Isomerase Skeletal muscle Transporter Rats Kinetics Glucose Enzyme medicine.anatomical_structure Intestinal Absorption Liver chemistry Phosphotransferases (Phosphomutases) Carrier Proteins Glycoprotein |
| Zdroj: | Glycobiology. 8:285-295 |
| ISSN: | 1460-2423 |
| DOI: | 10.1093/glycob/8.3.285 |
| Popis: | Direct utilization of mannose for glycoprotein biosynthesis has not been studied because cellular mannose is assumed to be derived entirely from glucose. However, animal sera contain sufficient mannose to force uptake through glucose-tolerant, mannose-specific transporters. Under physiological conditions this transport system provides 75% of the mannose for protein glycosylation in human hepatoma cells despite a 50- to 100-fold higher concentration of glucose. This suggests that direct use of mannose is more important than conversion from glucose. Consistent with this finding the liver is low in phosphomannose isomerase activity (fructose-6-P-mannose-6-P), the key enzyme for supplying glucose-derived mannose to the N-glycosylation pathway. [2-3H] Mannose is rapidly absorbed from the intestine of anesthetized rats and cleared from the blood with a t1/2of 30 min. After a 30 min lag, label is incorporated into plasma glycoproteins, and into glycoproteins of all organs during the first hour. Most (87%) of the initial incorporation occurs in the liver, but this decreases as radiolabeled plasma glycoproteins increase. Radiolabel in glycoproteins also increases 2- to 6-fold in other organs between 1-8 h, especially in lung, skeletal muscle, and heart. These organs may take up hepatic-derived radiolabeled plasma glycoproteins. Significantly, the brain, which is not exposed to plasma glycoproteins, shows essentially no increase in radiolabel. These results suggest that mammals use mannose transporters to deliver mannose from blood to the liver and other organs for glycoprotein biosynthesis. Additionally, contrary to expectations, most of the mannose for glycoprotein biosynthesis in cultured hepatoma cells is derived from mannose, not glucose. Extracellular mannose may also make a significant contribution to glycoprotein biosynthesis in the intact organism. |
| Databáze: | OpenAIRE |
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