1st Unit / Ch 4 Fibrous Proteins Flashcards
Collagen 4.1
In the collagen a chain shown, what amino acid (present at every third position) is represented by the black ball? What is special about this amino acid?
The black ball at every third position shown represents Gly. Gly is the smallest amino acid, having only an H for a side chain. Gly fits into the restricted space where the three a chains come together.
Collagen 4.1
Which is/are descriptors of type 1 collagen? It is:
A. a fibrous protein. TRUE .
B. an extracellular (secreted) protein. TRUE .
C. a fibril-forming collagen. TRUE .
Collagen 4.1
What targets the prepro - a chains of collagen to the RER?
An amino acid sequence at the N terminus ( N-terminal signal sequence ) targets proteins such as the prepro - a chains of collagen to the RER.
Collagen Synthesis 4.2
What enzyme catalyzes the reaction shown? Where does the reaction occur?
Prolyl hydroxylase, an enzyme of the RER, catalyzes the hydroxylation of Pro to Hyp
Collagen Synthesis 4.2
What is the function of the reaction in the formation of collagen?
Hydroxylation maximizes formation of the interchain H-bonds that stabilize the triple helical structure of collagen.
Collagen Synthesis 4.2
Which other amino acid undergoes the same posttranslational reaction during
collagen synthesis?
- *Lys** also undergoes posttranslational hydroxylation to Hyl (which is formed by lysyl hydroxylase ) during collagen
synthesis. [Note: Hyl is a substrate for O-glycosylation.]
Collagen Synthesis 4.2
A deficiency in vitamin C ( ascorbate ), the coenzyme for the reaction shown, causes , a disease characterized by the production of collagen with decreased tensile strength
causes scurvy. Vitamin C
is the coenzyme for both prolyl hydroxylase and lysyl hydroxylase . Without the additional stability provided by
Hyp and Hyl, collagen has decreased tensile strength. Patients with scurvy may have bruise-like ecchymoses
(shown) as a result of blood vessel fragility.
Collagen Synthesis 4.3
Does the removal of the N- and C-terminal propeptides from procollagen (as shown) occur intracellularly or extracellularly?
What is the fate of the triple-helical tropocollagen formed in the cleavage reaction?
Removal of the terminal N- and C-propeptides from procollagen occurs extracellularly and is catalyzed by N-terminal and C-terminal procollagen peptidases . The triple-helical tropocollagen molecules formed in the cleavage reaction spontaneously associate to form collagen fibrils that are organized into an overlapping parallel array. The array is then cross-linked to produce collagen fibers.
[ Note: The spontaneous association of tropocollagen is an
example of the hydrophobic effect.]
Collagen Synthesis 4.3
Why are the disulfi de bonds in the C-terminal propeptide domain of procollagen important for the formation of functional collagen?
The disulfi de bonds in the C-terminal propeptide domain bring the three _a chain_s into correct alignment for triple helix formation. They are important for the formation of functional collagen.
Collagen Synthesis 4.3
What name is given to the group of diseases that may result from defects in processing events during collagen synthesis?
Collagenopathies are diseases that may result from defects in collagen-processing events, such as removal of the terminal propeptides and hydroxylation of proline.
Collagen Synthesis 4.4
What enzyme catalyzes the oxidative deamination reaction shown?
Lysyl oxidase catalyzes the oxidative deamination of Lys to allysine.
Collagen Synthesis 4.4
Does the reaction occur within or outside of a cell? What is the function of the reaction?
The reaction occurs outside of a cell (extracellularly). It forms reactive aldehydes (such as allysine) that condense with Lys residues in neighboring collagen molecules to form the covalent
cross-links characteristic of mature collagen.
[ Note: Two allysine residues can form cross-links
via aldol condensation.]
Collagen Synthesis 4.4
Menkes syndrome is a disease of severe Cu2 + deficiency. Why is connective tissue fragility
characteristic of this syndrome?
Connective tissue fragility is characteristic of Menkes syndrome because lysyl oxidase is a Cu2 - requiring enzyme. Decreased activity of this enzyme, as a consequence of decreased
Cu2, would impair the final step in collagen synthesis.
[ Note: X-linked Menkes syndrome
( kinky hair disease ) is the consequence of a defect in the transporter that moves dietary Cu2+
out of intestinal cells. This decreases Cu2+ availability for the rest of the body. In addition to lysyl oxidase , other Cu2+ - requiring enzymes ( cytochrome c oxidase , dopamine hydroxylase ,
superoxide dismutase , and tyrosinase ) are affected.]
Collagenopathies 4.5
Which heritable collagen-based disease is characterized by stretchy skin, as shown? Which type of collagen is affected in this disease? Which type of collagen is mutated in the vascular form of this
disease that is associated with potentially lethal arterial rupture?
Classic Ehlers-Danlos syndrome ( EDS ) is characterized by stretchy skin . In classic EDS, type V collagen is affected. The vascular form of EDS, associated with potentially lethal arterial rupture, is
caused by mutations to type III collagen.
Collagenopathies 4.5
Which heritable collagen-based disease is characterized by bone fragility (as shown) and is the most severe form of the disease? Which type of collagen is affected in this disease?
Osteogenesis imperfecta ( OI ), a heritable collagen-based disease, is characterized by bone fragility. Shown at right is the most severe form of OI, which typically is lethal in the perinatal period. Type I collagen is affected in OI. [Note: A common mutation in OI results in the replacement of Gly, which prevents appropriate packing of the a chains in the triple helix.]
