Connective Tissue Flashcards Preview

Biochem > Connective Tissue > Flashcards

Flashcards in Connective Tissue Deck (44):
1

Proteoglycans

Core protein is covalently attached to multiple, long/linear chains of glycosaminoglycans

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Where are proteoglycans found?

Synovial fluid, arterial walls, bone/cartilage, ocular virtuous humor, and is a major component of the extra cellular matrix

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Functions of proteoglycans

Molecular sieves (due to largeness), give some flexibility to substances

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Glycosaminoglycans

Repeating disaccharide units found on proteoglycans Usually contain a hexosamine and uronic acid

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How do the types of glycosaminoglycans differ?

Monosaccharides in repeating units change

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Which glycosaminoglycan does not link covalently?

Hyaluronic acid

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What proteins to 5 of 7 glycosaminoglycans covalently link to?

Serine and Threonine

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Which amino acid does keratan sulfate I attach to?

Asparagine

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How does hyaluronic acid associate with proteins?

Noncovalent linkage

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Synthesis of proteoglycans

  1. Sugar attaches to serine/threonine
  2. UPD-sugar glycosyltransferases transfer monosaccharides from nucleotide-linked sugar to receptor
  3. 2 glycosyltransferases alt adding monosac.
  4. Sulfate groups added after sugars by PAPS
  5. Secreted and forms into ECM

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Proteoglycan aggregate

Formed by noncovalent interactions b/t the core protein and hyaluronic acid

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Glycoproteins

  • Usually shorter carb chains than proteoglycans
  • Carb portion is usually branched and not made of repeating disaccharides
  • Make up most of the proteins circulating in the blood

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Glycoprotein synthesis

  1. Carb monomers are added to protein (lumen of ER/Golgi)
  2. sugar added via O-linkage (ser, thr) or N-linkage (asn)
  3. Carb side chain extended by sequential addition of sugar residues to nonreducing end

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O-Linked Glycosides

  • Begin w/ N-acetyl-galactosamine to specific ser or thr side chain on protein

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N-linked Glycosides

  • Lipid-linked oligosaccharide is contracted (dolichaol molecules on the membrane)
  • sugars added to dolichol by membrane bound glycosyltransferases
  • Oligosaccharides transferred from dolichol to asn by protein-oligosaccharide transferase in ER

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Degredation of proteoglycans and glycoproteins

  • Lysosomes endocytose the molecules
  • Glycosidases degrade carb portion of molecules

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Endoglycosidase

Cleaves the carb chain to shorter oligosaccharides

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Exoglycosidase

Removes sugar residue from the nonreducing end

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Collagen Structure

  • Triple helix made of 3 alpha chain, left handed helices (3 residues per turn)
  • Chains wound together (right handed) and H-bonds stabilize
  • Glycine-X-Y is repeated pattern

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Proline and hydroxyproline: role in collagen helices

Increases rigidity in collagen helices

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Synthesis of Collagen

  1. Preprocollagen synth. (has a signal sequence and polypeptide extension removed from N&C terminals)
  2. triple helix formed from C-terminal bc had the ability to form both inter- and intrachain disulfide bonds

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Propel hydoxylase

  • Hydroxylates the proline molecules, making necessary hydroxyproline
  • Vitamin C and α-ketoglutarate are cofactors

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Lysine/hydroxylysine

  • Formed via Lysyl hydroxylase
  • Either lysine or hydrated form can be in Y position

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Interruptions

  • Areas of globular structures interspersed in the triple helical structure
  • Lack Gly-X-Y form
  • Ex: Collagen IV

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Type I and V of collagen

Skin, bone, tendon, blood vessels, cornea

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Type II of Collagen

Cartilage, intervertebral disks, nitrous body

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Type III of Collagen

Blood vessels, fetal skin

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Type IV of Collagen

Basement membrane

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Ehlers-Dalos Syndrome

  • Inheritied genetic disorder affecting collagen
  • Signs: hyperflexibility of skin, abnormal tissue fragility, increased joint mobility
  • 10 types

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Type IV of Ehlers-Dalos Syndrome

Most serious type that can cause ruptures of the bowl arteries due to abnormalities in type III collagen

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Type VI of Ehlers-Dalos Syndrome

Hysyl hydroxylase deficiency results in joint hypermobility/ocular rupture

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Type VIIC of Ehlers-Dalos Syndrome

Procollagen N-proteinase deficiency results in joint hypermobility (from abnormally thin, irregular collagen fibrils)

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Alport Syndrome

  • x and autosomal linked
  • Affects Type IV collagen fibers
  • Signs: hematuria, can developed ESRD due t orenal basal abnormaility 

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Scurvy

  • Vitamin C deficiency that affects collagen production (prolysyl and lysyl hydroxylase cofactor)
  • Signs: bleeding gums, subcutaneous hemorrhages, poor wound healing

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Elastin

Add elastic properties of extensibility and elastic recoil in tissue (stretching without tearing)

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Synthesis of Elastin

  • synthesized in a single tropoelastin molecule
  • No extention peptides in C/N terminals, Gly-X-Y, triple helices, or card portions

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Lysyl oxidase

  • involved with collagen processing
  • Also deanimates lysyl residues from the tropoelastin

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Desmosines

  • Major cross-link of elastin (CL is unique to elastin)
  • 3 lysine-derived aldehydes w/ an unmodified lysine
  • CL makes it highly insoluable and extremely stable

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Williams syndrome

  • Developmental disorder affecting CNS and connective tissue
  • 90% of subjects have elastin deletion – Probable cause of aortic stenosis found in condition

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Fibrillin

  • Large glycoprotein that is a structural component of microfibirls
  • Secreted into the ECM to be incorporated into insoluable microfibrils
  • Provides a scaffold for deposition of elastion

 

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Marfan Syndrome

  • Autosomal dominant – affects connective tissue
  • Signs: Tall, long digits, hyperflexibility of joints, cardiovascular problems
  • Fibrillin gene is deleted/missense mutations

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Fibronectin

  • Soluble glycoprotein found in large amounts in the ECM
  • Dimmer joined by disulfide bonds near C-terminal
  • Arg-Gly-Asp sequence (RGD) that binds to integrin
  • 7 binding sites doe heparin, fibrin, collagen, DNA, cell surface proteins

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Laminin

  • 3 distinct polypeptide chains linked together to form elongated cruciform shape
  • Binding site for Collagen IV, heparin, integrin
  • Primary component of basal lamina

44

Basal lamina components

Laminin, enactin, type IV collagen