Glycoproteins And Proteoglycans Flashcards
Where does N-glycosylation occur?
Only asparagine residues are N-glycpsylated in the rER.
- A mannose-rich oligosaccharide is first synthesized on a lipid that is bound in the rER membrane.
- All N-glycosylated proteins receive this precursor in one step to their asparagine residues
- A mannose rich oligosaccharide is synthesized bound to the lipid dolichol-PP. Dolichol has many isoprene units which anchor it in rER membrane
- This oligosaccharide precursor is transferred in one step to a specific asparagine residue of protein. Trimming of sugar residues starts in the rER lumen.
Complex glycoproteins and high-mannose glycoproteins are formed in…
The Golgi
Summarize complex and high-mannose glycoprotein formation
- Protein synthesis begins and the polypeptide chain is extruded into the rER
- A branched oligosaccharide is synthesized on dolicohol pyrophosphate
- The oligosaccharide is transferred from dolicohol to amide N of an asparagine residue of growing polypeptide chain
- Trimming of the carbohydrate chain begins as the protein moves forward through the rER
- The Golgi, further trimming and/or addition of monosaccharide pccurs.
This forms high mannose glycoproteins and complex glycoproteins
How are N- glycosylated glycoproteins transported out of the cell?
Are transported into lysosomes, secreted into the blood or incorporated into the cell plasma membrane
- Glycoproteins that are to be secreted from the cell remain free in the lumen. They are released when the vesicle fuses with cell membrane
- Glycoproteins that are to become components of the cell membrane are integrated into the membrane of the secretory vesicles that bud from the Golgi and fuse with the cell membrane
Describe I cell disease
- Caused by a deficiency of the ability to phosphorylate mannose
- Characteruzed by skeketal abnormalities, restricted joint movement, course facial features, and severe psychomotor impairment
- Death usually occurs by 8 years of age
Explain in detail transport of enzymes from the Golgi to lysosomes
-Lysosomal enzymes are N-linked glycoproteins that receive in the Cis-Golgi a mannose 6-P marker for transport into lysosomes. This mannose 6-P marker is formed by a specific phosphotransferase which recognizes all potential lysosomal enzymes that are meant to be transported into lysosomes
Mannose 6-P receptors in the trans-Golgi bind the marked enzymes and package them into vesicles for transport into lysosomes. The receptor is recycled and the enzyme is active inside of lysosomes after cleavage of the phosphate of the mannose 6-P
The deficiency of the mannose 6-P marker leads to I-Cell disease. The potential lysosomal enzymes are lacking in lysosomes and are instead secreted and found in plasma and urine . The disease manifests at birth and has often a fatal outcome at 4 years of age due to cardiopulmonary complications
What causes I-cell disease?
- Lysosomes lack their normal complement of several enzymes and in I-cell disease, many different molecules are not degraded and accumulate for,int inclusion bodies
- Diagnosis is Made by detection of inclusions in lymphocytes or cultured skin fibroblasts which is confirmed by lysosomal enzymes activity in blood plasma.
- Because children have some features in common with patients who have mucopolysaccharides or sphingolipidoses, I-cell disease is grouped as mucolipidoses Type II
Contrast the components of proteoglycans and glycoproteins ?
Proteoglycans contain mainly special sugars (GAGs) and a small amount of protein. O-glycosylation of the core protein.
Glycoproteins contain mainly proteins and a small amount of sugars which are often branched. O and N glycosylated protein
Where can O-linked glycostkation be found?
Serine of threonine residues
Hydroxylation-lysin residues in collagen
Where does N-glycosylation occurs?
Only Asparagine residues
Outline O-glycosyation of proteins
- The protein is synthesized on the rER and extrudes into its lumen.
- The first sugar is enzymatically transferred and linked directly to the OH-group of serine, threonine or hydroxylysine residues.
- Sugars in O-linkage are added individually directly to the protein mainly in the Golgi by glycosyl transferases bound to the Golgi membranes
- The enzymes involved act in a specific order and recognize the actual structure and add individually in the appropriate sugar
- O-Glycosylstion is used in the synthesis of proteoglycans, glycocalyx components, blood group substances and mucins
How are Blood types are O-linked glycoproteins
R is either a protein or a lipid (ceramide)
- Type O has no sugar linked to Gal of the H substance (zero)
- Type A has GalNAc linked to the Gal of the H substance
- Type B has galactose linked to the Gal of the H substance
- Type AB is a mixture of Type A and Type B structures
What are mucins? Are they proteoglycans or glycoproteins?
Mucins are NOT proteoglycans although they contain up to 50% carbohydrate. Mucins are special glycoproteins that contain more carbohydrates than other glycoproteins. The protein is rich in serine and threonine residues which leads to hundreds of sugars in O-linkage
Salivary mucins contain mainly only one N-acetylglucosamine linked to serine or threonine residues. This sugar binds Sialic acid (NANA) which results in mucins with many negative charges
How are mucus formed? What 8s the function of mucus?
Mucins and water leads to mucus which protects and lubricates many internal body surfaces
What is the key function of ocular mucus?
Retains epithelial moisture (tear film) . Avoids dry eye
What is the function of the nasal mucus?
- Regulates bacteria/particulate removal
- Provudes lubricity
