Lecture 39 Flashcards
(18 cards)
Collagen and Elastin function in the ____ ____ matrix, which means they are made within the cell and then secreted out.
EXTRA CELLULAR MATRIX.
Collagen genes are located ______ the genome.
THROUGHOUT
All collagens have _____-helical structure with the AA ___ in every third position.
Triple-helical
GLYCINE
Gly-X-Y structure of collagen is observed where X is usually ____ and Y is either hydroxy_____ or hydroxy_____.
X is usually PROLINE, and Y is either hydroxyPROLINE or hydroxyLYSINE.
In the process of making collagen in the cell, the mRNA is translated in the _____, then select _____ and _____ residues are hydroxylated, and then only _____ _____ residues are glycosylated. Next, these pro-alpha chains assemble, forming inter and intrachain ______ bridges at the _____-terminal. The triple helix structure is then formed by “zipper-like” folding from the _____-terminal to the _____-terminal, and the procollagen molecule is secreted into the ECM. There, the termini are cleaved, and the collagen molecules self-assemble to form cross-linked _______.
Collagen mRNA is translated in the CYTOSOL, then select PROLINE and LYSINE residues are hydroxylated, and then only HYDROXYLYSINE residues are glycosylated. Next, these pro-alpha chains assemble, forming inter and intrachain DISULFIDE bridges at the C-terminal. The triple helix structure is then formed by zipper-like folding from the C-terminal to the N-terminal, and the procollagen molecule is secreted into the ECM. There, the termini are cleaved, and the collagen molecules self-assemble to form cross-linked FIBRILS.
The hydroxylation of proline and lysine residues requires two cofactors, _____ and vitamin _____. Dietary deficiencies in the vitamin can cause _____, characterized by easily bruised skin, bleeding gums, loose teeth, “corkscrew hairs,” and poor wound healing.
Fe2+
VITAMIN C.
Scurvy
Lysyl _____ is the enzyme responsible for cross-linking collagen molecules, which requires _____ as a cofactor.
Lysyl OXIDASE is the enzyme responsible for cross-linking collagen molecules, which requires COPPER as a cofactor.
Copper deficiency leads to ______ disease, whereas Copper buildup leads to ______ disease.
Cu deficiency leads to Menke’s disease, and Cu buildup leads to Wilson’s disease.
OI (osteogenesis imperfecta) type I is the ____ severe, where as type II is the _____ severe.
Type I is the LEAST severe, whereas type II is MOST severe.
Type II, III, and IV OI arise from substitutions in the gene for ____1A1 or ____1A2 which results in the change from _____ to another AA with a bulky side chain. This prevents correct folding into the triple helix form. In these cases, most of the collagen that is made is misfolded and degraded, especially in the case of Type ___ (the most severe).
COL1A1
COL1A2
GLYCINE
Type II
Severity of the 4 types of OI is in this order ___>___>___>___. Keep in mind most cases arise from ______ mutations, but in some cases it can be inherited.
II>III>IV>I
Spontaneous
Whereas Types II, III, and IV OI arise from point mutations, Type I OI arises from a ______ mutation, so only a little collagen is made while most of the mRNA is degraded.
NONSENSE
____ coloring in sclera, short stature, multiple bone fractures, ____ legs and arms, early hearing loss, scoliosis, and/or kyphosis are characteristic of patients with Type III OI. Type I OI patients may have any of these, but are much more normal in phenotype.
BLUE
Bowed
Unlike Collagen, elastin has only a little hydroxy_____ and no hydroxy_____.
Elastin has only a little hydroxyPROLINE and no hydroxyLYSINE.
Unlike collagen, elastin interacts with _____ in the ECM. Mutations in _____ lead to Marfan syndrome, which shows a(n) _____ dominant mode of inheritance linked to the ____ gene on chromosome 15.
FIBRILIN
FIBRILIN
AUTOSOMAL dominant
FBN1 gene on chromosome 15.
Marfan syndrome patients are typically tall with _____dactyly, _____ excavatum, and dilation of ____. These patients typically die of ruptured arteries because of weakened arterial walls.
ARACHNOdactyly,
PECTUS excavatum
AORTA.
Lysyl oxidase (with ____ as a cofactor) acts on elastin as well, forming _____ cross-links (allysine residues), which confers elastin’s “stretchiness.”
Copper
DESMOSINE cross-links
Ehrlers-Danlos type ___ is the most severe, and can result in arterial or _____ rupture.
Type IV
Uterine
