Liberty University
Master of Medical Science: Biopsychology
BCHM 551
Assignment 1
Faith Sola
L28844810
September 15, 2019
Words: 630
1.Osteogenesis Imperfecta (OI) is an autosomal dominant inherited disorder. OI is characterized
by bone fragility and other connective tissue abnormalities like short stature or dentinogenesis
due to the defective synthesis of type I collagen, family history, and physical and radiographic
findings. The most common and less severe form of OI is characterized by normal OI type 1
stature, little to no deformity, hearing loss, dentinogenesis (in rare cases), and a blue sclera.
1
Unlike other forms of OI (types 2-5), has normal quality type 1 collagen, but the body OI type 1
produces insufficient amounts. The shortage of type 1 collagen results in a thinner than normal
pellucid sclera with pronounced blue choroidal veins portraying a distinct blue coloration.
2. The use of gel electrophoresis is to analyze posttranslational overmodification by analyzing
the slow migration of mutant chain or asymmetric shapes in CB peptides. On the other hand,
denaturation temperature (T ) values analyze collagen structure and stability. Since gel
m
electrophoresis is used to analyze posttranslational modifications, the mutation of a patient with
type 4 OI should occur during chain synthesis and association when thermal stability is
negatively affected. Chain synthesis and association is the first step in the collagen fiber
synthesis pathway and is essential for understanding how structural defects in collagen can cause
OI.1 It is important to note that substitutions of the obligatory glycine, causing structural effects,
do not affect collagen chain synthesis and association. Therefore, the structural defects of the
molecule can be visually insignificant until procollagen folding where structural mutations can
be weakly detected in gel electrophoresis if the N-terminal end of the molecule was mutated.1
This manifestation was demonstrated in two young patients with and : both type 1 type 4 OI
patients had low Tm values, but a slow migration of overmodified mutant chains, barely
detectable in gel electrophoresis due to weaker overmodification of the N-terminal of the
molecule chain.1
3. Posttranslational overmodification is the hallmark of structure mutations due to excessive
hydroxylation and glycosylation of lysine residues in procollagen folding. Procollagen folding
occurs in a zipper-like format from the C-terminal to the N-terminal end. If the mutation were to
occur on the N-terminal side, overmodification would be weak because folding proceeds from
the C-terminal to the mutation site where it stops. Therefore, the unfolded chain close to the N-
terminal would be overhydroxylated and overglycosylated causing milder OI symptoms. On the
contrary, if overmodification were to occur on the C-terminal side, prominent overhydroxylation
and overglycosylation would occur because of the large unfolded region on the procollagen chain
leading to severe and even lethal symptoms.
4. All lifeforms must maintain homeostasis in order to survive. Homeostasis of collagen fibers is
thermodynamically maintained. Such that if the thermal stability of collagen is not upheld, the
triple helix of collagen can denature at high temperature or can be quickly unfolded in low bodily
temperatures due to a decrease in the temperature (T ). This may explain why a denaturation m
large fraction of newly synthesized mutant collagen is degraded and never makes it into mature
fibers. As a result, the kinetics of fiber formation and collage melting may be disrupted, and
fibers may have to form quickly causing irregular collagen networks, low posttranslational
overmodification, improper mineralization, and brittle bones.
5. Bisphosphonates can be a beneficial treatment for patients with OI, however, long-term effects
of this treatment are still under investigation. When administered, bisphosphonates are engulfed
1
by osteoclasts, or a type of bone cell that absorbs bone tissue, reducing their activity. However,
bisphosphonates do not affect the synthesis or destruction of abnormal collagen. Therefore, your
child’s bone density may increase, resulting in increased height and decreased fractures, but their
bone structure is not expected to have better quality than before drug administration. Even in
some cases, oral bisphosphonate administration did not portray any beneficial effects compared
to controls. In addition to bisphosphonates, physical therapy and frequent appointments with
your child’s orthopedic surgeon is recommended to analyze the effects of the bisphosphonates,
gross motor control, and maximize their skills for independent living.
References
1. Leikin S, Flor-Cisneros A. Osteogenesis imperfecta. In: Glew R, Rosenthal M, eds.
Clinical Studies in Medical Biochemistry. 3rd ed. Oxford University Press; 2007:30-41.
