PTMs part 2 Flashcards
What are mucins and what amino acids are they rich in? What does this allow?
• Mucins (composes mucous) are a large family (20 genes in humans) of heavily glycosylated proteins
o Rich in serine, threonine and hydroxyproline enabling O-linked glycosylation (via hydroxyl group)
o Cysteine-rich regions (intra-molecular disulfide cross-links) found at N- and C-termini
What is the impact of glycosylation in mucins?
o Glycosylation makes mucins highly resistant to secreted bacterial proteases and proteolysis in general
o Able to contain water (moist environment)
Glycans are very hydrophilic
o Glycosylation and cross-links enable the formation of a sticky, moist gel layer (also enables aggregation)
How can epithelial cell cancers be predicted? Why?
• Epithelial cell cancers can be diagnostically predicted by the presence of altered mucin glycans in the plasma
o Loss of normal topology and polarization of peitohelial cells in cancer results in secretion of mucins in the bloodstream
o Glycans may be altered due to rapid cell division in cancers (timing is everything in glycans)
• Involvement in cancer-
o Because the cells divide rapidly, the proteins miss the action of enzymes that go down into these pathways
What are all cells covered in?
• All cells are covered in a complex array of glycans
Where are cell surface and secreted glycan proteins assembled?
• Cell surface and secreted (ECM) glycan-proteins are assembled in the ER-golgi
What is the most complex of all PTMs and why?
- Glycosylation is the most complex of all PTMs and encompasses a broad range of single and multi-sugar modifications (linear, branched)
- Glycans generate much more combinatorial diversity than amino acid sequence of other PTMs
Is glycosylation a biochemically efficient process?
• Many enzymes (glycosylatransferases/glycosidases) in a complex, inefficient biochemical process
What are glycosyltransferases?
o Glycosyltransferases- enzymes that add sugars
What are glycosidases?
o Glycosidases- enzymes that remove sugars
What are the structural units of glycans?
o Monosaccharides are the structural units of glycans
What are glycans?
Glycan- a generic term for a sugar or assembly of sugars, in free form or attached to another molecule, used interchangeably with (oligo)saccharide or carbohydrate
What is a monosaccharide? Where is its first carbon?
A monosaccharide is a carbohydrate that cannot be hydrolyzed into a simple form. It has a potential carabonyl group at the end of the carbon chain (an aldehyde group) or at an inner carbon (a ketone group). These two types of monosaccharides are therefore named aldoses and ketoses, respectively. Free monosaccharides can exist in open-chain or ring forms.
• Carbon 1- anomeric carbon: where it is attached to a hydroxyl group and directly to oxygen
Which structures are commonly found in N- and O-glycans?
o Monosaccharides commonly found in N- and O-glycans
What are the different types of monosaccharides?
Pentoses Hexoses Hexosamines Deoxyhexoses Sialic acids (Sia)
What are pentose monosaccharides?
Pentoses- five-carbon neutral sugars e.g. D-xylose (Xyl)
What are hexose monosaccharides?
Hexoses- six-carbon neutral sugars e.g. D-glucose (Glc), D-galactose (Gal) and D-mannose (Man)
What are hexosamine monosaccharides?
Hexosamines- hexoses with an amino groupa t the 2-position, which can either free or, more commonly, N-acetylated e.g. N-acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-galactosamine (GalNAc)
• Building blocks of glycosylation
What are deoxyhexose monosaccharides?
Deoxyhexoses- six-carbon neutral sugars without the hydroxyl group at the 6-position (e.g. L-fucose [Fuc])
What are sialic acid monosaccharides?
Sialic acids (Sia)- family of nine-carbon acidic sugars, of which the most common is N-acetylneuraminic acid (neu5Ac, also sometimes called NeuAc)
What modifications can the hydroxyl groups of different monosaccharides be subject to?
The hydroxyl groups of different monosaccharides can be subject to phosphorylation, sulfation, methylation, O-acetylation or fatty acylation
How is a glycosidic bond formed? How are these subsequently labelled?
• Glycosidic bond formation
o Formation of a disaccharide between glucose and fructose= sucrose
o Two monosaccharides are brought together such that two hydroxyl groups are close to each other
o In an enzyme-catalysed reaction (a glycosyltransferase), a water molecule is eliminated, leaving a bond between C1 of glucose and C4 of fructose (an alpha 1,4 bond)
Forms the glycosidic bond
o Glycosidic bonds are labelled alpha or beta depending on the anomeric configuration of the C1 involved in the glycosidic bond
Up is beta
Down is alpha
What is maltose?
o Maltose is 2 Glc in an alpha linkage
What is lactose?
o Lactose is 2 Glc in a beta configuration
Can humans digest sugars in an alpha or beta linkage better?
Humans are more able to digest sugars in an alpha linkage