Collagen Post-translational Modifications

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Questions and Answers

Which types of collagens are known to form fibril-associated collagens with interrupted triple helices?

Types IV, V, VI

Types I, II, III

Types VIII, X, XI

Types IX, XII, XIV (correct)

What is primarily responsible for the symptoms of Scurvy?

Mutations in collagen genes

Deficiency of lysyl oxidase

Excessive hydroxylation of proline

Lack of ascorbic acid (Vitamin C) (correct)

What is a characteristic feature of Ehlers-Danlos syndrome?

Hyperactivity and mood swings

Joint stiffness and short stature

Hypermobility and stretchy skin (correct)

High blood pressure and obesity

Which collagen type is associated with forming hexagonal networks?

Type X Signup and view all the answers

What is a significant consequence of non-hydroxylated collagen chains?

Immediate degradation inside the cell Signup and view all the answers

Which type of collagen is primarily found in the basement membrane?

Type IV Signup and view all the answers

What type of collagen forms beaded filaments?

Type VI Signup and view all the answers

Which gene mutations have been linked to collagenopathies?

Over 1000 mutations in 23 genes Signup and view all the answers

What disorder occurs due to crosslinking deficiency in collagen?

Ehlers-Danlos syndrome Signup and view all the answers

Which symptom is NOT typically associated with Scurvy?

Joint stiffness Signup and view all the answers

What is a primary consequence of glycation in collagen molecules?

Fixed orientations due to cross-linking Signup and view all the answers

Which enzyme is involved in the process of glycosylation of collagen?

Galactosyl transferase Signup and view all the answers

Which statement accurately describes the effect of glycation on cells’ recognition of collagen?

Glycation prevents cells from recognizing collagen Signup and view all the answers

In which condition is an excessive level of sugar in tissue most likely to occur?

Diabetes mellitus Signup and view all the answers

What happens to collagen replacement in the body over the course of one year?

3 kg of collagen is replaced Signup and view all the answers

What role do proteolytic enzymes play in collagen metabolism?

They are involved in collagen degradation Signup and view all the answers

What is a characteristic of Cathepsin K in relation to collagen?

It is involved in collagen degradation Signup and view all the answers

Which family of enzymes is specifically noted for breaking peptide bonds in collagen?

Cysteine proteinases Signup and view all the answers

Which process describes the digestion of collagen in controlled cellular environments?

Controlled cathepsin cannibalism Signup and view all the answers

What happens to collagen synthesis and degradation equilibrium typically after wound healing?

It is regained after 3-5 weeks Signup and view all the answers

Which of the following statements is true regarding N-linked glycoproteins?

They are synthesized and modified in the rough endoplasmic reticulum and the Golgi apparatus. Signup and view all the answers

What type of modification occurs with O-linked glycoproteins?

Enzymatic addition of a single sugar residue to the hydroxyl side chain of serine or threonine. Signup and view all the answers

Which of the following glycosylation types involves the sugar connecting to a carbon atom of an amino acid?

C-glycosylation Signup and view all the answers

What is the main functional role of glycoproteins within biological systems?

To facilitate cellular interactions and act as signaling molecules. Signup and view all the answers

Which of the following best describes the properties of glycoproteins in an extracellular matrix?

They are temporary proteins that play roles during development and remodeling processes. Signup and view all the answers

Which subunit combinations exist in Laminin based on its structure?

There are 45 different combinations from three types of subunits. Signup and view all the answers

What is the role of glycosylation in collagen structure?

To facilitate the interaction between collagen and hydrophobic environments Signup and view all the answers

Which enzyme is responsible for the glycosylation of hydroxylysine residues in collagen?

Galactosyl transferase Signup and view all the answers

What results from the phosphorylation of serine or threonine residues in collagen?

Increased stability of the triple-helix Signup and view all the answers

What structural motif is used to illustrate the location of phosphorylated residues in collagen chains?

Gly-X-Y Signup and view all the answers

How does glycosylation affect the interaction of collagen with other molecules?

It stabilizes the fibril-forming process through hydrophobic arrangements Signup and view all the answers

Which property is essential for the kinases involved in collagen modification?

Recognition of unfolded collagen chains Signup and view all the answers

What is a consequence of phosphorylation in collagen peptides?

Enhanced ability to form stable triple-helixes Signup and view all the answers

What role does galactosyl transferase play specifically within collagen biochemistry?

Catalyzing the addition of galactose to hydroxylysine residues Signup and view all the answers

In terms of collagen synthesis, what is a primary effect of modifications such as glycosylation and phosphorylation?

To promote the formation of stable collagen structures Signup and view all the answers

What component of the elastic fiber provides stability and allows for stretching and recoiling?

Cross-linked elastin Signup and view all the answers

Which of the following statements regarding the interactions between collagen and elastic fibers is true?

There are limited physical interactions between collagen and elastic fibers. Signup and view all the answers

What is the primary composition of proteoglycans?

5-15% proteins and 85-95% carbohydrates Signup and view all the answers

Which glycosaminoglycan is characterized by its long, non-sulfated polysaccharidic chain?

Hyaluronic acid Signup and view all the answers

What role do negatively charged proteoglycans play in the extracellular matrix?

They can bind water and form hydrated matrices. Signup and view all the answers

Which amino sugar is involved in the formation of glycosaminoglycan disaccharides?

N-acetylgalactosamine Signup and view all the answers

What type of bond links glycosaminoglycans to the core protein in proteoglycans?

O-glycosidic bond Signup and view all the answers

Which enzyme is responsible for the acetylation of amino groups in glycosaminoglycans?

N-acetyltransferase Signup and view all the answers

What characteristic of glycosaminoglycans primarily influences their ability to form hydrated matrices?

Their negative charge Signup and view all the answers

Which functional property of proteoglycans aids in regulating cell migration?

Binding of water and ions Signup and view all the answers

Study Notes

Post-translational Modifications

Glycosylation in Collagen: Galactosyltransferase and glycosyltransferase enzymes add sugar molecules to hydroxylysine residues in collagen. This is crucial for fibril formation as it ensures hydrophobic faces of sugar molecules interact with collagen fibrils.
Phosphorylation in Collagen: Serine or threonine residues in the X position of the Gly-X-Y triplet in unfolded collagen chains are phosphorylated by kinases. This phosphorylation increases triple-helix stability, allowing for the formation of stable collagen structures.

Collagen Types

Fibril-forming collagens: Types I, II, III, V, XI, XXIV, XXVII
Fibril-associated collagens with interrupted triple helices: IX, XII, XIV, XVI, XIX, XX, XXI, XXII, XXVI
Collagens forming hexagonal networks: VIII, X
Basement membrane collagen: IV
Collagens forming beaded filaments: VI
Anchoring fiber-forming collagens: VII
Plasma membrane-spanning collagens: XIII, XVII, XXIII, XXV
Collagens with unique domain organization: XV, XVIII

Collagen Diseases

Scurvy: Caused by lack of vitamin C, disrupting proline and lysine hydroxylation, leading to unstable collagen and its degradation.
Collagenopathies: Genetic diseases caused by mutations in collagen genes, affecting collagen synthesis and its ability to form fibers. These include over 1000 mutations in 23 genes coding for 13 collagen types.
Ehlers-Danlos syndrome: Caused by deficiency of the enzyme lysyl oxidase, leading to issues with collagen cross-linking. Symptoms include joint hypermobility, stretchy skin, and aneurysms.

Glycation vs. Glycosylation in Collagen

Glycation: Non-enzymatic covalent addition of sugar molecules to collagen, negatively impacting collagen structure and function. Occurs in conditions like diabetes and chronic inflammation.
Glycosylation: Enzymatic post-translational modification of collagen, adding sugar molecules to hydroxylysine residues. Essential for collagen fibril formation.

Dynamic Equilibrium of Collagen

Synthesis: Occurs constantly, with an average of 3 kg of collagen replaced yearly in the body.
Catabolism/Degradation: Occurs through phagocytosis, collagenolysis, and extracellular enzymes like proteases.
Healing Wounds: Exhibit an equilibrium between synthesis and degradation after 3-5 weeks.

Cysteine Proteinase

Cathepsin K: Expressed in osteoclast lysosomes and released during bone remodeling and resorption. Degrades elastin, collagen, and gelatin in bone and cartilage.
Cathepsin B & L: Cleave collagen types II, IX, XI and destroy cross-linked collagen matrix at low pH

Elastin Fibers

Formation: Elastin molecules combine with fibrillin, forming elastic fibers with a core of elastin surrounded by fibrillin-containing microfibrils.
Elasticity: Random-coil domains in elastin molecules allow the network to stretch and recoil.

Fibrous Networks in Extracellular Space

Structure: Collagen and elastic fibers form interconnected networks providing tissue integrity and mechanical stability.
Function: Confer mechanical resistance through separate mechanisms, interacting with other matrix macromolecules.

Proteoglycans

Structure: Composed of glycosaminoglycans (GAGs) covalently linked to core proteins.
Properties: Negatively charged, attracting water and forming hydrated matrices.
Function: Provide space, allow compressibility, act as filters for ions, and regulate cell migration and adhesion.

Proteoglycans Structure

GAGs: Consist of long polysaccharide chains with repeating disaccharide motifs.
Linkage: GAGs are covalently linked to core proteins through O-glycosidic bonds.
Monomers: Bound non-covalently to hyaluronic acid molecules.
Hyaluronic Acid: A long, non-sulfated polysaccharide chain.

Glycosaminoglycan Disaccharides

Building blocks: Repeating disaccharide units consisting of an amino sugar (N-acetylglucosamine or N-acetylgalactosamine) and an acidic sugar (glucuronic or iduronic acid).
Modifications: Amino groups are often subject to modifications like acetylation and sulfation.

Types of Glycoproteins

N-linked glycoproteins: Glycoproteins with carbohydrates (14 or more sugar residues) attached to asparagine residues.
O-linked glycoproteins: Glycoproteins with a single sugar residue added to the hydroxyl side chain of serine or threonine residues.
P-glycosylation: Sugar attached to the phosphorus of phosphoserine.
C-glycosylation: Sugar attached to the carbon atom of an amino acid (e.g. mannose to tryptophan).
Glypiation: Glycophosphatidylinositol (GPI) glycolipid attached to the carbon terminus of a polypeptide.

Glycoprotein Formation

Synthesis: Proteins are synthesized in the rough endoplasmic reticulum.
Oligosaccharide Chain Synthesis: Glycosyltransferases in the Golgi apparatus synthesize oligosaccharide chains from nucleotide sugars.
Attachment: Glycosylation - the enzymatic attachment of sugar to protein.
Timing: Glycosylation can occur co-translationally (N-glycosylation) or post-translationally.

Glycoprotein Function

Secretion: Glycoproteins can be secreted from the cell into the extracellular matrix.
Incorporation: They can be incorporated into the cell membrane.
Diversity: Glycoproteins have diverse roles in development, growth, homeostasis, and survival.
Cellular Interactions: They are crucial for cellular interactions, serving as signaling molecules, receptors, and components for binding cells and extracellular matrix.

Temporary Glycoproteins

Timing: Glycoproteins are not permanent structures in the extracellular matrix, but play important roles during:
- Embryonic development
- Normal tissue development
- Tissue repair after damage
- Tissue remodeling

Laminin

Structure: Composed of α, β, and γ subunits, with multiple combinations possible.
Diversity: Up to 45 different combinations of these subunits can exist.

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Description

Explore the critical roles of post-translational modifications like glycosylation and phosphorylation in collagen stability and formation. Learn about various types of collagens and their functionalities. This quiz will challenge your knowledge of these essential biochemical processes.