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1. collagen 2. elastin 3. glycoproteins 4. proteoglycans |
| list the 4 components of extra-cellular matrix |
| collagen |
| fibrous protein, abundant secondary structure, long cyllindrical shape, low water solubulity, structural rather than dynamic role |
| repeating structures that are non-covalenly linked |
| what does abundant secondary structure mean? |
| in cells |
| where is ECM made? |
| glycoproteins |
| mostly protein, modified with carbs, no repeated structures, component of ECM |
| collagen |
| 25% of all protein in the boy, 74% of protein in skin |
| proteoglycans |
| component of ECM, mostly carbs modified by proteins (less protein that others) |
| tropocollagen |
| basic structural unit of collagen |
| tropocollagen |
| more easily extractable from tissues of young animals, because older animals have more cross-linking |
| 110 daltons |
| avg molecular wt of an amino acid |
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alpha1(I) x 2, alpha2(I) x 1 bone, skin, tendon, cornea |
| what is collagen type I composition and distribution |
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alpha1(II) x 3 cartilage, intervretebral disc, vitreous body |
| what is collagen type II composition and distribution |
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alpha1(III) x 3 fetal skin, cardiovascular system |
| what is collagen type III composition and distribution |
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alpha1(IV) x 3 or alpha2(IV) x 3 basement membrane, lens capsule |
| what is collagen type IV composition and distribution |
| 3 |
| how many peptide chains in tropocollagen |
| Glycine ~1/3, Proline |
| most abundant aa in collagen (first 2) |
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Hyp (4-hydroxyproline) Hyl (5-hydroxylysine) |
| unusual amino acids found in collagen |
| Gly-Pro-Hyp |
| what is the recurring tri-peptide sequence in all collagens? |
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| structure of Hyp |
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| structure of 5-hydroxy lysine |
| prolyl hydroxylase |
| what enzyme forms Hyp? |
| must be on amino side of glycyl residue |
| where must the prolyl residue be to undergo 4-hydroxylation to form Hyp? |
| no, only the ones on the amino side of glycyl |
| is free proline a substrate for prolyl hydroxylase? |
| iron in Fe2+ ferrous, reduced state (need vitamin C for this -ascorbate) |
| what is present at the enzyme active site of prolyl hydroxylase and what is needed to keep it in the reduced state? |
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Scurvy, the integrity of blood vessels are compromised due to improper/insufficient collagen formation causing bloody gums |
| what is hypovitaminosis C, and how does it present? |
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| what does the equation for Hyp formation look like? |
| galactosyl transferase and glucosyl transferase |
| what enzyme is required for hydroxylysine glycosylation? |
| before helix formatin |
| when does glycosylation of Hyl residues occur relative to helix formation? |
| alpha1 |
| most common type of constituent peptide in tropocollagen |
| dehydroascorbate, it is a non-specific antioxidant that removes oxygen. it is peed out |
| what does ascorbate become after oxidation, and what happens if it builds up? |
| collagen is more tightly wound(d= 3.3 coll vs 3.61 aplha), and more extended (pitch)9.5 vs 5.4 alpha |
| compare collagen to a right handed aplha helix |
| steric repulsion of pyrrolidone rings of proline residues (no intra chain hydrogen bonds like alpha helix) |
| what are the stabilizing forces of tropocollagen? |
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1. interstrand hydrogen bonds 2. hydrogen bonds between water and Hyp |
| what are the stabilizing forces of mature collagen? |
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donor: backbone NH groups of Gly acceptor: backbone CO groups direction = transverse |
| what is the donor/acceptor of inter-strand hydrogen bonds of mature collagen and what direction? |
| ppg has lower melting point(24) due to less H bonds phg has higher melting point(58) due to more H bonds |
| compare pro-pro-gly chains to pro-hyp-gly(like in tropocollagen) chains |
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n: intrachain disulfide bonds, collagen domain C: inter + intra chain disulfide bonds (sulfide bonds from cysteine S residues) |
| what structures exist at n terminal peptides of tropocollagen and at c terminal? |
| extracellular space |
| where is the conversion of procollagen to tropocollagen? |
| hypermobile joints, stretchable skin, short stature, due to deficiency of procollagen N-protease which cuts of n terminal peptide |
| what is Ehlers-Danlos syndrome Type VII |
| quarter staggered |
| tropocollagen fibrils associate and form collagen fibrils, how are they arranged? |
| cross linking in mature collagen |
| what is the difference between mature collagen and collagen fibrils? |
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| draw the aldol cross-link reaction, what does it require? |
| aldol cross links 2 lysyl residues by making them into 2 allysine (1 allysine link to 1 lysine) dependent on copper, b6 and oxygen |
| what is lysyl oxidase and what is it dependent on? |
| lysine + allysine -> shiff base (aldimine) -> (reduced) lysinorleucine double bond is lost between nitrogen and carbon |
| what are the steps in the schiff base and lysinorleucine cross-link reactions? |
| extremely fragile collagen in animals caused by ingestion of the seeds of sweet pea (Lathyris odoratus). the toxic agent = beta aminopropionitrile which inhibits lysyl oxidase (the cross linking enzyme) |
| what is lathyrism? |
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1. transcription(nucleus) 2. polypeptide synthesis (in cyto with ER) 3. hydroxylation/glycosylation (in ER) 4. procollagen(triple helix formatin in ER) |
| what are the first 4 steps of collagen formation? |
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5. secretion (golgi) 6. tropocollagen formation (extracellular) 7. collagen fibril formation (extracellular) 8. formation of cross-links to yield mature collagen fibrils (extracellular |
| what are the last 4 steps of collagen formation? |
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aka brittle bone disease/lobstein syndrome. bone fragility stemming from abnormalities in collagen molecule forming the bone matrix. disorder of type 1 collagen. mostly autosomal dominant molecular defect: mutations confined to structural genes for constituent peptides of collagen |
| what is osteogenesis imperfecta? |
| proteoglycans |
| 95% polysaccharide, 5%protein, polyanions that bind water and cations. |
| glycosaminoglycans (GAGs) or mucopolysaccharides |
| what is the main component of proteoglycans? |
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hexosamine: glucosamine or galactosamine uronic acid: beta d glucuronate or alpha-l-iduronate |
| what are the 2 main components(monmers) of GAGs |
| cushion against mechanical impact, they associate with water molecules |
| what is the function of proteoglycans? why do they weigh more? |
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1. hyaluronic acid 2. chondroitin sulfates 3. dermatan sulfate 4. keratan sulfate 5. heparin and heparan sulfate |
| what are the 5 classes of glycosaminoglycans? |
| hyaluronic acid found in synovial fluid |
| what is the most abundant GAG? |
| structure of chondroitin 6 sulfate |
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| structure of dermatan sulfate |
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| structure of karatan sulfate |
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| structure of hyaluronate |
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| structure of heparin/heparan sulfate |
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| GlcUA, GlcNAc |
| what are the 2 components(sugar/acid) of hyaluronic acid? |
| GlcUA, GalNac (6S or 4S) |
| what are the 2 components(sugar/acid) of chondroitin sulfate? |
| IdUA*****, GalNac-4S |
| what are the 2 components(sugar/acid) of dermatan sulfate? |
| Gal, GlcNac-6S |
| what are the 2 components(sugar/acid) of keratan sulfate? |
| GlcUA-2S, GlcNS-6S |
| what are the 2 components(sugar/acid) of heparin, heparan sulfate? |
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1.HS has more N acetate, fewer sulfate groups (couterintuitive) 2. lower degree of O-sulfation 3. some iduronic acid in place of glucuronic acid |
| what are the 3 main differenes between heparin and heparan sulfate? |
| mucopolysaccharidoses |
| what is the name for the lysosomal storage diseases? |
| dysostosis multiplex |
| feature of all mucocpolysaccharidoses, name for morphologic abnormalities of many parts of the skeleton |
| Hurler syndrome, DS and HS (remember the severity by Hurler syndrom makes you want to hurl, but scheie is okay) |
| most severe form of alpha l-iduronase deficient disorders. usually patients die before age 10. (What GAG is excreted also?) |
| Scheie syndrome, DS and HS |
| mild form of alpha l iduronase deficiency, what is excreted? |
| hurler-scheie syndrome HS and DS |
| intermediate severity form of alpha l iduronase enzyme deficiency, what is excreted? |
| iduronate sulfatase, DS and HS |
| what enzyme is deficient in hunter syndrome and what is excreted? |
| heparan n sulfatase(n-sulfamidase), only HS is excreted |
| what enzyme is deficient in Sanfillipo syndrom A-form, and what is excreted? |