What is the effect of hyp residues on collagen chains?
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They greatly increase the potential for hydrogen bonding between chains.
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What is the effect of hyp residues on collagen chains?
They greatly increase the potential for hydrogen bonding between chains.
What are proteoglycans?
A special class of glycoproteins that are heavily glycosylated (95%).
What do proteoglycans consist of?
A core protein with one or more attached glycosaminoglycan chains.
What is the diameter of collagen fibrils mentioned?
1 mm.
How is tropoelastin modified to form elastin?
It is highly cross-linked to form an insoluble complex.
Where does hydrogen bonding occur in collagen?
Between the amide N of glycine residues in the central axis and the carbonyls of adjacent chains.
What is located at the C-terminal end of the triple helical region of the bovine a1(I) collagen chain?
The amino acid sequence.
What types of collagen are mentioned?
Types I, II, III, V, IX, and X.
What structural feature reflects the periodic composition of collagen fibers?
The cross striated structure of collagen fibers.
What did James Lind recommend to prevent scurvy?
The inclusion of greens, fresh vegetables, and ripe fruits in the diet.
What enzyme does b-aminoproprionitrile block?
Lysyl oxidase.
What is the structure of Collagen IV's amino-terminal domain?
It has a short non-helical amino-terminal domain.
How many collagen molecules coil together to form a superhelix?
Three collagen molecules.
What role do telopeptides play in collagen structure?
They participate in covalent crosslinking.
What are hyp and pro in the context of collagen?
They are amino acids that contribute to the structure of collagen.
What type of bonding occurs between a glycine residue and a proline residue of different chains?
Inter-chain hydrogen bonding.
What is Ehlers-Danlos syndrome (EDS)?
A heterogeneous group of generalized connective tissue disorders resulting from inheritable defects in the metabolism of fibrillar collagen molecules.
What is the structural unit of collagen?
Tropocollagen, a supercoil made up of 3 helices.
What is the significance of inter-chain hydrogen bonding in collagen?
It contributes to the stability and structure of collagen fibers.
What is the structural form of collagen?
Collagen forms a 3-stranded collagen superhelix.
What is the role of 5-hydroxylysine (HyLys) in collagen?
It serves as a site for glycosylation.
What is the length of each unit of tropocollagen?
About 300 nm.
What is elastin primarily composed of?
Soluble tropoelastin protein containing primarily glycine and valine, along with modified alanine and proline residues.
Who was James Lind?
A Scottish physician who identified remedies for scurvy.
What is the structure of each collagen molecule?
Each molecule is composed of a left-handed helix.
What is the primary amino acid composition of collagen?
35% Gly, 11% Ala, 21% Pro and Hyp.
What is the consequence of decreased Lysyl Oxidase activity in Menkes disease?
Defective collagen formation.
Where are elastic fibers composed of elastin found?
In the lungs, walls of large arteries, and elastic ligaments.
What percentage of total body protein does collagen constitute?
About 25 – 35%.
Which genes are mutated in Types I through IV of Osteogenesis imperfecta?
COL1A1 and COL1A2 genes.
What is a key physical property of collagen?
It has great tensile strength.
What chronic exposure occurs in the normal lung regarding elastin?
Alveoli are exposed to low levels of neutrophil elastase from activated and degenerating neutrophils.
What are the main components that collagen is a part of?
Fascia, cartilage, ligaments, tendons, bone, and skin.
What percentage of collagen residues are made up of hyp and pro?
25%.
What is Ehlers-Danlos syndrome?
A group of 10 different collagen deficiency diseases.
What type of collagen is primarily found in the basement membrane?
Collagen IV.
Are collagen helices classified as alpha helices?
No, they are not alpha helices.
What is the appearance of collagen fibers in an electron micrograph?
They appear as long, thin, and wavy structures.
What is one of the biochemical lesions in scurvy?
Defective hydroxylation.
What dictates the types and organization of collagen molecules in the body?
The structural role collagen plays in a particular organ.
Where are collagen and elastin found in the body?
In skin, connective tissue, blood vessel walls, and the sclera and cornea of the eye.
What type of collagen structure is found in tendons?
Tight parallel structure.
What does Hyp stand for in the collagen sequence?
4-hydroxyproline.
What is the pitch of the collagen helix?
0.94 nm.
What is the incidence of Marfan syndrome?
1 in 10,000.
Where are collagen precursors formed?
In fibroblasts, osteoblasts of the bone, and chondroblasts of cartilage.
What should one know about the various types of collagen?
The different types of collagen and their specific sites of synthesis.
What is the width of each unit of tropocollagen?
About 1.5 nm.
What type of protein is collagen due to the presence of carbohydrates?
A glycoprotein.
What are covalently bonded to some hydroxy lysine residues in collagen?
Carbohydrates.
What is the most common interchain cross-link in elastins?
Desmosine cross-links.
What is the primary function of collagen in the skin?
To provide strength and support.
How much weight can collagen fibrils of 1 mm diameter support?
10 kg.
What condition might Paganini have suffered from?
Marfan's syndrome.
What is the unique secondary structure of collagen?
It is distinct from an alpha helix.
What role does collagen play in tissues and organs?
It contributes to their stability and maintains structural integrity.
What is required for the hydroxylation of lysine and proline?
α-ketoglutarate, O2, ascorbic acid, and Fe2+ as a cofactor.
In which tissue is fiber forming collagen primarily found?
Tendon.
How is collagen arranged in bone?
Arranged at an angle.
What is glycosylation in collagen synthesis?
The addition of galactose and glucose to some hydroxylysine residues.
What condition results from the destruction of connective tissue in alveolar walls?
Emphysema.
What is Osteogenesis imperfecta commonly known as?
Brittle bone disease.
Which collagens are classified as fibril-forming?
Collagens I, II, III, V, and X.
What causes Type I Osteogenesis Imperfecta?
Decreased production of α1 and α2 chains.
What is the molecular composition of Type III collagen?
[α1(III)]3
What is the molecular composition of Type XI collagen?
[α1(XI)α2(XI)α3(XI)]
What is the typical arrangement of tropocollagen molecules in collagen fibrils?
A staggered array.
In which tissues are Type III collagen fibers prevalent?
In more distensible tissues, such as blood vessels.
What is the approximate molecular weight of tropoelastin?
~65 kDa.
What is the composition of collagen in terms of amino acids?
Collagen is composed of 35% Gly, 11% Ala, and 21% Pro and hydroxyPro.
How many mutations have been identified in collagen-related genes?
More than 1,000 mutations.
What can cause Ehlers-Danlos syndrome?
Deficiency of collagen-processing enzymes or mutations in the amino acid sequences of collagen types I, III, or V.
How long after Lind's advice was it adopted by the British Navy?
About forty years later.
Which amino acids are often involved in the hydrogen bonding of collagen?
Proline and hydroxyproline.
What specific food did Lind urge sailors to include in their diet?
Lemon juice.
What is the function of the carboxyl-terminal globular NC1 domain in Collagen IV?
It is highly conserved and involved in polymerization.
What type of helix is the collagen helix?
Left-handed and not an alpha-helix.
What is the diameter of a tropocollagen molecule?
Close to 1.5 nm.
Which enzymes are involved in the hydroxylation process?
Lysyl-5-hydroxylase and prolyl-4-hydroxylase.
What is a common characteristic of the skin in patients with Ehlers-Danlos Syndrome?
Skin is velvety and fragile, with severe scarring from minor trauma.
What type of collagen structure is present in the vitreous humor?
Gel-like structure.
What mutation is associated with Type IV EDS?
Mutation in COL3A1, leading to abnormal collagen III.
What is the composition of type II collagen?
Three α1 chains (α1³).
What results from variations in the amino acid sequence of the α chains?
Structural components with slightly different properties.
What happens to processed mature mRNA after transcription?
It is exported to the cytosol for translation by ribosomes.
Where are Type I collagen fibers primarily found?
In supporting elements of high tensile strength, such as tendons and cornea.
What is unique about the structure formed by Types IV and VII collagen?
They form a three-dimensional mesh rather than distinct fibrils.
What major structure do Type IV collagen molecules contribute to?
Basement membranes, by assembling into a sheet or meshwork.
What is Menkes disease?
A condition caused by impaired copper absorption and transport due to defective Menkes protein.
What is gelatin derived from?
Gelatin is derived from collagen.
What percentage of all whole-body proteins does collagen constitute?
25% - 35%.
What type of secondary structure does collagen have?
A unique secondary structure distinct from an alpha helix.
What is the most clinically important mutation in Ehlers-Danlos syndrome?
Mutations found in the gene for type III collagen.
What is required for the hydroxylation of Proline and Lysine in collagen?
Vitamin C.
Which genes are commonly mutated in 40% to 50% of EDS patients?
COL5A1 or COL5A2 (type V collagen gene).
What is a key characteristic of collagen and elastin as fibrous proteins?
They are water insoluble and provide tensile strength.
What are the clinical manifestations of Alport Syndrome?
Defective glomerular filtration, eye problems (e.g., retinopathy, lens dislocation), and sensorineural deafness.
What is gelatin derived from?
Collagen.
Which joints are commonly hypermobile in Ehlers-Danlos Syndrome?
Shoulders, patellae, and ankles.
What is the resulting molecule after the cleavage of registration peptides from procollagen?
Tropocollagen.
What serious complications are seen in Type IV EDS?
Arterial, intestinal, and uterine rupture.
Why are children with Epidermolysis bullosa referred to as 'butterfly children'?
Because their skin is very delicate and fragile, similar to that of a butterfly.
Which gene is mutated in Marfan syndrome?
Fibrillin-1 gene on chromosome 15q21.
Which residues are hydroxylated during collagen biosynthesis?
Selected proline and lysine residues.
When does Osteogenesis Imperfecta typically present?
In early infancy with fractures secondary to minor trauma.
What structures are Type II collagen molecules restricted to?
Cartilaginous structures.
What type of tissue is collagen primarily found in?
Skin.
What compound found in Lathyrus odoratus seeds contributes to Lathyrism?
b-aminoproprionitrile.
What percentage of proteoglycans is glycosylated?
95%.
Who is an example of a person with Ehlers-Danlos syndrome?
The 'India-rubber man' of circus fame.
What amino acids make up approximately 30% of collagen residues alongside Glycine?
Proline or Hydroxyproline (HyPro).
What are some symptoms of Menkes disease?
Brittle kinky hair, growth retardation, and hypotonia.
What happens to elastic fibers when they are stretched?
They can be stretched to several times their normal length.
What causes Alport Syndrome?
Defective synthesis and processing of type IV collagen.
What type of molecule is collagen?
An insoluble glycoprotein (protein + carbohydrate).
How does Collagen IV polymerize?
It polymerizes into a disulfide-bonded polygonal network via tetramerization and dimerization.
What is the primary structure of collagen polypeptide represented by?
The sequence G – X – A, where G is glycine, X is proline or hydroxyproline, and A is an amino acid.
What are the short terminal portions of the polypeptides in typical fibrillar collagens called?
Telopeptides.
Which amino acids are primarily found in elastin?
Glycine, alanine, and valine.
What is the composition of type I collagen?
Two α1 chains and one α2 chain (α1²α2).
What is a notable feature of the fingers in Ehlers-Danlos Syndrome?
Patients may have 'double-jointed' fingers.
What is the effect of oxidation and deamination of hydroxylysine in collagen synthesis?
It has a net oxidative effect and forms covalent cross-links.
Which enzyme catalyzes the oxidation and deamination of hydroxylysine?
Lysine oxidase (or catalase).
Where is Type I collagen primarily distributed?
Bone, dermis, tendon, ligaments, and cornea.
What type of linkages are present in mature collagen?
Extensive covalent cross linkages between individual collagen molecules.
What is Lathyrism?
A condition characterized by abnormalities of bones, joints, and blood vessels.
What does an electron micrograph of collagen reveal?
The detailed structure and organization of collagen fibers.
What type of bonding is absent in collagen helices?
Intra-helical hydrogen bonding.
When did James Lind publish his findings on scurvy?
In 1753.
What is the molecular mass of tropocollagen?
~285 kDal.
What forms a triple-helical collagen molecule?
Three helical polypeptide units twist together.
What is osteogenesis imperfecta?
A condition characterized by abnormal (fragile) bone formation in human babies.
Who provided a vivid description of scurvy in 1536?
Jacques Cartier.
What is the helical structure of collagen?
A left-handed helical structure with three residues per turn.
What is the repeating sequence found in collagen?
Gly -- Pro/HyPro - X.
What is the composition of tropoelastin?
A linear polypeptide composed of about 700 amino acids, primarily small and nonpolar.
What can destroy elastin in alveolar walls?
Proteolytic activity of neutrophil elastase if unopposed by α1-AT.
What enzyme catalyzes the cleavage of registration peptides from procollagen?
Procollagen peptidases.
How does collagen contribute to development?
It plays an important role in tissue and organ development.
How many separate chains are involved in the collagen triple helix?
3 separate chains.
What type of disorder is Marfan syndrome?
A connective tissue disorder affecting the skeleton, heart, and eye.
How does smoking affect the risk of emphysema?
It increases the risk.
What does FACIT stand for?
Fibril-associated collagens.
What is a common eye-related issue in Marfan syndrome?
Subluxation of lenses, typically upward and temporally.
What is the molecular composition of Type V collagen?
[α1(V)α2(V)α3(V)]
What forms a desmosine cross-link in elastin?
Three allysyl side chains plus one unaltered lysyl side chain from the same or neighboring polypeptides.
What is the primary structure of collagen?
Collagen has a distinct tertiary and quaternary structure.
What role does elastin play in the body?
It is a major protein component of tissues that require elasticity, such as arteries, lungs, bladder, skin, and elastic ligaments and cartilage.
What percentage of collagen residues are Glycine?
~30%.
What enzyme converts amine groups of lysine to reactive aldehydes in elastin?
Lysyl oxidase.
What is the repeating tripeptide sequence in collagen?
Gly - X - Y, where X is often Pro and Y is often Hyp.
What is the repeating sequence found in Collagen IV?
A long Gly-X-Y repeat domain with numerous small interruptions.
What are the main characteristics of Ehlers-Danlos Syndrome (EDS)?
Hypermobile joints, hyperextensible skin, and fragile tissues susceptible to trauma.
What type of matrix is associated with collagen in cartilage?
Cartilaginous matrix.
What symptoms did Jacques Cartier describe in his men suffering from scurvy?
Loss of strength, purple spots on skin, rotten gums, and falling teeth.
What is the genetic mutation associated with Type VI EDS?
Mutation in lysyl hydroxylase.
Do Types V through VII of Osteogenesis imperfecta have collagen I mutations?
No, they do not have collagen I mutations but have a similar phenotype.
What is the role of Type VII collagen in the skin?
It forms structural links between the epidermis basement membrane and the fibrillar collagen in the upper dermis.
How many residues are there per turn in the collagen helix?
3 residues per turn.
What is another name for Osteogenesis Imperfecta (OI)?
Brittle bone syndrome.
Where does the transcription of collagen genes occur?
In the nucleus.
What is the first step after the synthesis of the prepro-α chain?
It is targeted into the lumen of the RER for hydroxylation.
What are anchoring fibrils collagens used for?
To anchor structures in the extracellular matrix.
What is the function of basement membrane collagens?
They provide support and anchorage for epithelial cells.
What can be seen as collagen fibers in the electron microscope?
Bundles of 3-stranded supercoils of tropocollagen.
What are collagenopathies?
Genetic diseases resulting from defects in collagen fiber synthesis.
What can result from defects in collagen fiber synthesis?
An inability of collagen to form fibers properly.
Which two amino acids are involved in inter-chain hydrogen bonding in this context?
Glycine and proline.
What is elastin?
A connective tissue protein with rubber-like properties.
How many genes are involved in collagen types related to collagenopathies?
22 genes coding for 12 collagen types.
Which collagen types are associated with Ehlers-Danlos syndrome mutations?
Collagen types I, III, or V.
How many amino acid residues does each collagen helix consist of?
Approximately 1000 amino acid residues.
What initiates the synthesis of pre-procollagen?
Chains of pre-procollagen are synthesized on ribosomes.
What is elastin synthesized from?
A precursor called tropoelastin.
What holds the three polypeptide α chains of collagen together?
Hydrogen bonds.
What process involves the secretion of procollagen molecules into the extracellular space?
Exocytosis.
What is a characteristic feature of Type VI EDS?
Severe kyphoscoliosis.
What is observed in the bone on microscopy for Types V through VII of Osteogenesis imperfecta?
Abnormal bone.
What is the structure of collagen in the cornea?
Stacked transparent structure.
What is a common symptom of patients with Dystrophic Epidermolysis Bullosa (DEB)?
Severe blistering of the skin.
What are the main classifications of collagens?
What process forms collagen fibrils from tropocollagen molecules?
Self-assembly or polymerization.
What recent development has been observed in some patients with Type II Osteogenesis imperfecta?
Some have lived into young adulthood.
What genetic mutations are commonly found in patients with severe Osteogenesis imperfecta?
Mutations in the gene for pro-α1 or pro-α2 chains of type I collagen.
How is collagen transported to the extracellular matrix?
Through secretary vesicles and exocytosis.
What is the result of the action of lysyl oxidase on lysine in elastin?
The spontaneous formation of desmosine cross-links.
What is the repeating tripeptide sequence in collagen?
Gly - X - Y, where X is often Pro and Y is often Hyp.
What is affected in Alport Syndrome?
The basement membrane.
What does collagen form?
A three-stranded superhelix.
What happens to the gums in individuals with scurvy?
They become rotten, causing flesh to fall off and teeth to loosen.
What important roles does collagen play in cellular processes?
Cell differentiation, polarity, and movement.
What role do proline and hydroxyproline play in collagen?
They provide stiffness to the polypeptide chain.
What is the role of α1-antitrypsin in the lungs?
It is the most important inhibitor of neutrophil elastase.
What joint issues are frequently observed in Ehlers-Danlos Syndrome patients?
Frequent sprains or subluxation of larger joints, either spontaneously or after slight trauma.
What is the molecular composition of Type I collagen?
[α1(I)2α2(I)]
What is a serious complication associated with the vascular subtype of Ehlers-Danlos Syndrome?
Spontaneous visceral or arterial ruptures.
What type of collagens form networks?
Network-forming collagens.
What is the effect of common mutations in Osteogenesis imperfecta on collagen structure?
They replace glycine residues with amino acids that have bulky side chains, preventing proper triple-helical conformation.
Where is Type XI collagen primarily distributed?
Cartilage and vitreous body.
What is Osteogenesis imperfecta (OI)?
A genetic disorder characterized by fragile bones.
What type of superhelix is formed by the coiling of collagen helices?
A right-handed superhelix.
What is the approximate length of a tropocollagen molecule?
Approximately 300 nm.
What occurs when the stretching force on elastic fibers is relaxed?
They recoil to their original shape.
What are the characteristics of bone in Osteogenesis imperfecta?
Decreased number of trabeculae and cortical thickness, leading to wormian bone.
What causes Epidermolysis bullosa?
Mutation, defect, or deficiency of Type VII collagen.
What amino acids constitute about 1/6 of the total collagen sequence?
Proline and hydroxyproline.
What characteristic does the triple-helical collagen molecule have regarding bending and rotation?
It has some bending stiffness and does not undergo rotation.
What additional amino acids is elastin rich in?
Proline and lysine.
What type of genetic inheritance does Marfan syndrome follow?
Autosomal dominant; 25% new mutations.
What is the most severe form of Osteogenesis imperfecta?
Type II.
What are common causes of death in patients with Type II Osteogenesis imperfecta?
Respiratory problems, often leading to pulmonary hypoplasia.
What stabilizes collagen fibrils during their formation?
Cross-linkage between adjacent tropocollagen molecules.
What are other collagens with unique functions?
Collagens that do not fit into the other categories and have specialized roles.
What are the two main types of collagen mentioned?
Fiber forming collagen and nonfibrous collagen.
How many types of collagen are included in the collagen superfamily?
More than 25 collagen types.
How many amino acids are there per turn in the collagen helix?
3 amino acids per turn.
What is the approximate length of the α chains in collagen?
About 1,000 amino acids long.
What is the significance of hydroxylation in collagen?
It is crucial for collagen stability, and its defect leads to scurvy.
What is formed during the assembly of α-chains in procollagen?
Disulfide bonds between registration peptides at both ends of the pre-procollagen.
Which carbohydrates are associated with collagen?
Glucose and galactose.
What is the structure formed by the three supertwisted chains of collagen?
A triple helix.
How are various types of collagen formed?
By combining different α chains.
What is the role of fibrillin in the body?
It is a glycoprotein that forms a sheath around elastin.
What sugars are involved in the glycosylation of collagen?
Glucose and galactose.
What is the role of transfer vesicles in collagen biosynthesis?
They transfer procollagen polypeptide to the Golgi for further modification.
What is the result of improperly formed collagen in Osteogenesis imperfecta?
Collagen is structurally abnormal.
What type of helical structure do alpha chains of collagen adopt?
A left-handed helical structure.
What happens when there is a deficiency in Type VII anchoring fibrils?
It impairs the adherence between the epidermis and the dermis.
What role do glycoprotein microfibrils, such as fibrillin, play in elastin synthesis?
They function as a scaffold for the deposition of tropoelastin.
What happens to some lysyl side chains of tropoelastin?
They are oxidatively deaminated by lysyl oxidase, forming allysine residues.
What are common features of Osteogenesis Imperfecta?
Retarded wound healing and a kyphotic appearance due to a rotated and twisted spine.
What is the molecular composition of Type II collagen?
[α1(II)]3
What are the physical characteristics of patients with severe Osteogenesis imperfecta?
Numerous fractures, severe bone deformity, small stature, and underdeveloped lungs.
What is the positive thumb sign associated with Marfan syndrome called?
Steinberg sign.
What genetic defects can lead to emphysema and cirrhosis?
Defects in α1-antitrypsin.
What percentage of Ehlers-Danlos Syndrome patients experience aortic root dilatation?
1/3 of patients.
What is Type I Osteogenesis Imperfecta called?
Osteogenesis imperfecta tarda.
Where is Type II collagen found?
Cartilage, vitreous body, and nucleus pulposus.
How may Osteogenesis Imperfecta be suspected prenatally?
If ultrasound detects bowing or fractures of long bones.
What is another name for Type II Osteogenesis imperfecta?
Osteogenesis imperfecta congenita.
Where is Type III collagen primarily distributed?
Skin, vessel wall, and reticular fibers of most tissues (lung, liver, spleen, etc.).
What are common physical characteristics of individuals with Marfan syndrome?
Tall with long extremities and hypermobile joints.
What are some specific signs associated with Marfan syndrome?
Long tapering fingers and toes, aortic incompetence, and dissecting aortic aneurysm.
What is the positive wrist sign associated with Marfan syndrome called?
Walker sign.
What percentage of total collagens do fibril-forming collagens represent?
90%.
What is the role of transmembrane collagens?
They span the cell membrane and are involved in cell signaling.
Where is Type V collagen found?
Lung, cornea, bone, fetal membranes, together with Type I collagen.
What are collagen and elastin?
Common fibrous proteins of the extracellular matrix that serve structural functions in the body.
What is collagen?
A structural protein that provides strength and support to various tissues in the body.
What is involved in the biosynthesis of collagen?
The process includes synthesis and post-translational modifications.
What are collagenopathies?
Genetic disorders that affect collagen structure and function.
Who is Dr. Bart Dzudzor?
A professional associated with the study or research of collagen.
What are the main functions of collagen and elastin?
Collagen provides structural support, while elastin allows tissues to stretch and recoil.
