lecture 9 Flashcards
Proteoglycans, Glycoproteins and the Extracellular Matrix
what is the glycocalyx?
a network of glycoproteins and proteoglycans that extends outward from the surface of the cells.
what other name does the glycocalyx go by?
extracellular matrix (ECM), but the ECM has more than just carbohydrates
describe the functions of the glycocalyx?
it protects the outer surface of the cell from mechanical disruption and allows cell to attach itself to other surfaces.
how does the glycocalyx help to serve a similar role to the cell wall?
bacteria for example have a cell wall but eukaryotic cells only have a plasma membrane, the ECM/glycocalyx serves a role similar to a cell wall
does the glycocalyx serve a specific purpose for individuals? How does it relate to the immune system? Name some examples?
The glycocalyx is unique to every individual and serves as a key mechanism for immune system to ID which cells belong and which are foreign; bacterial infection and different blood types
where are proteins containing carbohydrates found (glycoproteins)?
outside the cell, in membrane enclosed vesicles within the cell, in the cell membrane
where are glycolipids found?
in the cell membrane
what are glycosaminoglycans (GAGs)?
heteroglycans like mixed monosaccharides with linear, regular, repeating disaccharide units
what are the five classes of GAGs?
- hyaluronic acid (HA)
- condroitin sulfates (CS)
- heparin and heparin sulfates (HS)
- keratan sulfate (KS)
- dermatin sulfate (DS)
name functions for HA?
cell migration in embryogenesis, morphogenesis, wound healing
name functions for CS?
formation of the bone, cartilage, cornea
name functions for HS?
Heparin - anticoagulation via binding with antithrombin III, causes release of lipoprotein lipase from capillary walls
Heparin sulfates - component of skin fibroblasts and aortic wall; commonly found on cell surfaces
name functions for keratin sulfate (KS)?
transparency of cornea
name functions for derma tin sulfate (DS)?
transparency of cornea and binds LDL to plasma walls
GAGs have very similar structures, T/F?
T
describe the GAGs in terms of sugars?
one of the two monosaccharides is always an amino sugar:glucosamine or galactosamine. Both are acetylated except in heparin where it is sulfate
what are the two possible amino sugars that make up one of the two monosaccharides in a GAG?
glucosamine or galactosamine
which of the monosaccharides is the amino sugar not acetylated?
heparin
so we identified what one of the two monosaccharides would be in a GAG: an amino sugar, now identify the other one, which is?
alduronic acid (glucuronic acid and/or its isomer iduronic acid?except KS where it is galactose
all GAGs except this GAG has hydroxyls substituted with sulfate, name it?
Hyaluronic Acid (HA)
all GAGs have hydroxyls substituted with sulfate, T/F
F, except HA
what is the purpose of multiple sulfation for GAGs?
it allows sequences to have specific recognition functions which recognize other proteins especially growth factors
what is formed after GAGs are attached to core proteins; name an example
Proteoglycans; chondroitin sulfate
how are proteoglycans linked to core proteins?
linked to serine or threonine residues by a glycosidic linkage (called an O-linked)
are the link trisaccharide the same or different? what varies?
the link trisaccharide is always the same, thought the AB group varies as does n, which is large and is predominately a carbohydrate
what are proteoglycans?function?
core protein covalently attached to many long, linear chains of GAGs, highly variable in structure but all contain one or more type of GAGs; Excreted from cells: key component of extracellular matrix – interacts directly with proteins of extracellular matrix: collagen, fibronectin and laminin. It also acts as a lubricant and as a shock absorber expanding and compressing easily
where else can proteoglycans be found beside the ECM?
found in synovial fluid of joints, vitreous humor of the eye, arterial walls, bone and cartilage
what is the purpose of the meshwork produced by the proteoglycans?
it limits exposure of cell surface to various agents
what is the type of structure that proteoglycans adapt?
a bottle brush structure
proteoglycans aggregate with what other molecule to form much larger structures? how does having negative charges affect structure?
glycososaminoglycans; the presence of many negative charges leads to charge repulsion and GAGs being extended and the charged groups like -OH cause the GAGs to be highly hydrated
what is the difference between a proteoglycan and a glycoprotein?
proteoglycan are mostly carbohydrates with a little protein, a glycoprotein is a protein with a little bit of carbohydrate
what type of linkages can a glycoprotein have?
they can be N-linked or O-linked
describe how the N-linked saccharides are attached?what about the O-linked?
they are attached via the amide nitrogen of asparagine, the only one used. More complex than O-linked, common core, highly varied structure which also indicates location and function; the O-linked saccharides are attached to hydroxyl group of serine, threonine, or hydroxylysine (oxidized), hence the O atom of the side chain. Usually 1-3 sugars and the carb affects recognition and structure
what are amino sugars?examples?
they contain an amine group in place of one hydroxyl, i.e Beta-D- glucosamine and Beta-D-galactosaminem (note the amine group on carbon 2, and the reversed -OH group on carbon 4, opposite to carbon 1 for Beta-D-Glucosamin and same side when comparing carbon 4 to carbon 1; other examples are Beta-L-Fucose, Beta-D-Acetylgalactosamine, Beta-D-acetylglucosamine, and Sialic Acid (Sia)
what is the function of the o-linked saccharides of glycoproteins?Name and example?
to force the protein to adopt an extended conformation, these resemble bristle brushes which extend the functional domains up out of the glycocalyx; Beta-Galactosyl-1,3-alpha-N-acetylgalactosamine which is an O-linked glycoprotein
why is the Bristle Brush structure important?
it plays a protective roll and keeps agents away from the surface and can also play a receptor role making it easier for agents to find a receptor above the complicated ECM
describe N-linked oligosaccharides?
the oligosaccharides can alter the chemical and physical properties of proteins, stabilize protein conformations and/or protect against proteolysis
what happens when you cleave the monosaccharide unit from N-linked glycoprotein?
it targets them for degradation in the liver
how simple are O-linked glycoproteins in of carbs and how they are added?
they have simple carbohydrate groups and are added one by one by post translational modification enzymes
how complex are N-linked oligosaccharides of glycoproteins?
the core glyco group is synthesized first in which the dolichol phosphate is the holder for the glyco group (cytosol) and this is transferred over to nascent protein (ER lumen) where additional synthesis and modifications are made as necessary.
where are glycosylated proteins sent? what about the ones destined to be degraded?
outer surface of the plasma membrane or out of the cell; sent to the lysosomes in which KEY MANNOSE residues are phosphorylated SIGNALING for DEGRADATION
so in reference to lysosomes degrading phosphorylated glycoproteins what happens if these lysosomal enzymes are lacking? example?
they develop inclusion bodies, the lysosomes fill with the GAGs (in some cases organs and in blood) since they cannot be degraded and will expand, since this causes cellular damage, dysfunctional development and mental retardation occur in children; mucopolysaccharideosis
what are inclusion bodies?
dark spots within cells which become more numerous and larger with passing time, causing cell function to be compromised.
T/F, proteoglycans and other glycosaminoglycans they are made of can be degraded, recycled and used for synthesis of new proteoglycans?
T
In terms of GAG degradation, each GAG does not have its own enzyme for degradation, T/F? Explain
F, each GAG does and this occurs in the lysosomes
what is mucopolysaccharideosis?
One of a series of inherited metabolic disorders affecting a type of complex carbohydrate called a mucopolysaccharide that is deposited in body tissues because the person lacks the specific enzyme needed to metabolize it; know that mucopolysaccharidoses are diseases
involving enzyme deficiencies in the metabolism of glycosoaminoglycans.
what is the ECM comprised of?
fibrous proteins like collagens and elastins embedded in amorphous ground substance made of basal lamina, integrins, and matrix metalloproteinases (MMPs)
what is the ground substance made of?
hyaluronic acid, proteoglycans, adhesive proteins, laminin and fibronectin
what is important to note about the integrin involved in the ECM?
they bind adhesive protein and span membranes so they provide contact between the ECM and cytoskeleton
why are matrixmetalloproteinases (MMP)important to the ECM? Example?
they cleave one or more components of the ECM and are responsible for normal and pathological tissue remodeling; cancerous cells have increased MMP activity breaking the ECM barrier allowing them to escape
what do fibrous proteins provide to the ECM?
tensile strength and elasticity;
what does the ground substance provide the ECM?
deformability, resilience, and cohesion
why are integrins important to the ECM? examples of importance?
they are transmembrane proteins that bind to specific ECM components at the extracellular surface and also to the cell cytoskeleton inside the cell undergoing conformational changes communicating outside chemical and mechanical stimulation to inside the cell; cell motility, cell shape changes, cell response to mechanical events
