Direct utilization of mannose for mammalian glycoprotein biosynthesis |
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Authors: | Alton G; Hasilik M; Niehues R; Panneerselvam K; Etchison JR; Fana F; Freeze HH |
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Institution: | The Burnham Institute, La Jolla, CA 92037, USA. |
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Abstract: | 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.
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