The Endoplasmic Reticulum Golgi Apparatus Are the Major Sites of Glycosylation

As indicated in Figure 47-9, the endoplasmic reticulum and the Golgi apparatus are the major sites involved in glycosylation processes. The assembly of Dol-P-P-oligosaccharide occurs on both the cytoplasmic and lu-minal surfaces of the ER membranes. Addition of the oligosaccharide to protein occurs in the rough endo-plasmic reticulum during or after translation. Removal of the Glc and some of the peripheral Man residues also occurs in the endoplasmic reticulum. The Golgi apparatus is composed of cis, medial, and trans cisternae; these can be separated by appropriate centrifugation procedures. Vesicles containing glycoproteins appear to bud off in the endoplasmic reticulum and are transported to the cis Golgi. Various studies have shown

ROUGH ENDOPLASMIC RETICULUM

ROUGH ENDOPLASMIC RETICULUM

CMP-

CMP-

Figure 47-9. Schematic pathway of oligosaccharide processing. The reactions are catalyzed by the following enzymes: ©, oligosaccharide:protein transferase; ©, a-glucosidase I; ®, a-glucosidase II; (3), endoplasmic reticulum a1,2-mannosidase; CD, W-acetylglu-cosaminylphosphotransferase; ((3, W-acetylglucosamine-1-phosphodiester a-W-acetylglu-cosaminidase; CD, Golgi apparatus a-mannosidase I; CD, W-acetylglucosaminyltransferase I; CD, Golgi apparatus a-mannosidase II; CD, W-acetylglucosaminyltransferase II; CD, fucosyltrans-ferase; ®, galactosyltransferase; <55, sialyltransferase. The thick arrows indicate various nucleotide sugars involved in the oveall scheme. (Solid square, W-acetylglucosamine; open circle, mannose; solid triangle, glucose; open triangle, fucose; solid circle, galactose; solid diamond, sialic acid.) (Reproduced, with permission, from Kornfeld R, Kornfeld S: Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem 1985;54:631.)

that the enzymes involved in glycoprotein processing show differential locations in the cisternae of the Golgi. As indicated in Figure 47-9, Golgi a-mannosidase I (catalyzing reaction 5) is located mainly in the cis Golgi, whereas GlcNAc transferase I (catalyzing reaction 6) appears to be located in the medial Golgi, and the fucosyl, galactosyl, and sialyl transferases (catalyzing reactions 9, 10, and 11) are located mainly in the trans Golgi. The major features of the biosynthesis of N-linked glycoproteins are summarized in Table 47-10 and should be contrasted with those previously listed (Table 47-9) for O-linked glycoproteins.

Table 47-10. Summary of main features of N-glycosylation.

• The oligosaccharide Glc3Man9(GIcNAc)2 is transferred from dolichol-P-P-oligosaccharide in a reaction catalyzed by oligosaccharide:protein transferase, which is inhibited by tunicamycin.

• Transfer occurs to specific Asn residues in the sequence Asn-X-Ser/Thr, where X is any residue except Pro, Asp, or Glu.

• Transfer can occur cotranslationally in the endoplasmic reticulum.

• The protein-bound oligosaccharide is then partially processed by glucosidases and mannosidases; if no additional sugars are added, this results in a high-mannose chain.

• If processing occurs down to the core heptasaccharide (Man5[GlcNAc]2), complex chains are synthesized by the addition of GlcNAc, removal of two Man, and the stepwise addition of individual sugars in reactions catalyzed by specific transferases (eg, GlcNAc, Gal, NeuAc transferases) that employ appropriate nucleotide sugars.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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