Biochemsitry Wk 7

Question 1

Collagen types

Answer 1

The collagens can be organized into three groups, based on their location and functions in the body

Question 2

Structure of collagen

Answer 2

Collagen is rich in proline and glycine, both of which are important in the formation of the triple- stranded helix.

Proline facilitates the formation of the helical conformation of each α chain because its ring structure causes “kinks” in the peptide chain.

Glycine, the smallest amino acid, is found in every third position of the polypeptide chain. It fits into the restricted spaces where the three chains of the helix come together.

Question 3

Hydroxyproline and Hydroxylysine

Answer 3

Collagen contains hydroxyproline (hyp) and hydroxylysine (hyl), which are not present in most other proteins.

These residues result from the hydroxylation of some of the proline and lysine residues after their incorporation into polypeptide
chains (post translational modification)

Question 4

Glycosylation

Answer 4

The hydroxyl group of the hydroxylysine residues of collagen may be enzymatically glycosylated.

Most commonly, glucose and galactose are sequentially attached to the poly - peptide chain prior to triple-helix formation

Question 5

Synthesis and secretion of collagen

Answer 5

Look at GOODNOTES

Question 6

Scurvy

Answer 6

A disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans.

Scurvy often presents itself initially as symptoms of malaise and lethargy, followed by formation of spots on the skin, spongy gums, and bleeding from the mucous membranes.

Patients with scurvy also often show bruises on the limbs as a result of subcutaneous extravasation of blood due to capillary fragility

Question 7

Function of Vit C aka absorbic acid

Answer 7

Antioxidant + facilitates iron absorption by reducing it to Fe2+
Necessary for hydroxylation of proline and lysine in collagen synthesis

Symptoms of scurvy- swollen gums, easy bruising, poor wound healing, haemorrhages, weakened immune response, petichae

Question 8

Ehlers-Danlos syndrome

Answer 8

This disorder is a group of generalized connective tissue disorders that result from inheritable defects in the metabolism of fibrillar collagen molecules.
It is a group of inherited disorders that affect your connective tissues — primarily your skin, joints
and blood vessel walls.

Procollagen peptidase

Question 9

Ehlers-Danlos syndrom

Answer 9

EDS can result from a deficiency of collagen-processing enzymes (for example, lysyl hydroxylase or procollagen peptidase), or from mutations in the amino acid sequences of collagen types I, III, or V.

Hyper mobility and stretchy skin

Question 10

Ehlers-Danlos syndrome

Answer 10

The most clinically important mutations are found in the gene for type III collagen.
Collagen containing mutant chains is not secreted, and is either degraded or accumulated to high levels in intracellular compartments.
Because collagen type III is an important component of the arteries, potentially lethal vascular problems occur.

Question 11

Symptoms of ehlers Danlos

Answer 11

Hyper mobility type -( joint instability) most common type
Classical type- (joint and skin symptoms) caused by mutation in the type V collagen
Vascular type- (fragile tissues including vessels) e.g aorta - muscles and organs that are prone to rupture mutations in type 3 procollagen

Uterus is prone to rupture

Question 12

Osteogenesis Imperfecta

Answer 12

This disease, known as brittle bone syndrome, is a group of inherited disorders distinguished by bones that easily bend and fracture.
• They are around eight (8) types of OI but type 1 is the most common
• Most patients with severe OI have mutations in the gene for either the pro-α1 or pro-α2 chains of type I collagen.
• The most common mutations cause the replacement of glycine residues (in – Gly–X–Y–) by amino acids with bulky side chains. The resultant structurally abnormal pro-α chains prevent the formation of the required triple- helical conformation.

Question 13

Osteogenesis Imperfecta

Answer 13

Type I OI is called osteogenesis imperfecta tarda. The disease is the consequence of decreased production of α1 and α2 chains.
• It presents in early infancy with fractures secondary to minor trauma, and may be suspected if prenatal ultrasound detects bowing or fractures of long bones.
• Type II OI is called osteogenesis imperfecta congenita, and is the most severe. Patients die of pulmonary hypoplasia in utero or during the neonatal period.

Question 14

Symptoms of OI

Answer 14

Bones- multiple fractures and scoliosis
I (eye)- blue sclerae
Teeth- dental imperfections dentinogenesis imperfecta
Ear- conductive hearing loss

Question 15

Menkes disease

Answer 15

X linked recessive connective tissue disease caused by impaired copper absorption and transport due to defective menkes protein

So decrease of Lysol oxidase -> defective collagen
Brittle “kinky” hair-> tyrosinase needs copper important in the regulation of melanin
Growth retardation
Hypotonia
Increase risk of cerebral aneurysms

Tyrosinase- needs copper

Question 16

Elastin

Answer 16

Elastin is a connective tissue fibrous protein with rubber-like properties.
• Elastic fibers composed of elastin and glycoprotein microfibrils are found in the lungs, the walls of large arteries, and elastic ligaments.
• They can be stretched to several times their normal length but recoil to their original shape when the stretching force is relaxed.

Question 17

Tropoelastin

Answer 17

Tropoelastin is precursor of elastin
• It contains two types of alternating domains.
• Hydrophilic sequence that is rich in lysine and alanine residues.
• Hydrophobic sequence that is rich in valine, proline, and glycine
• Elastin is an insoluble protein polymer generated from a precursor, tropoelastin
• Elastin is also rich in proline and lysine but contains scant hydroxyproline and hydroxylysine

Question 18

Synthesis of elastin

Answer 18

Look at GOODNOTES

Question 19

What is Marfan syndrome

Answer 19

Autosomal dominant - tall with long extremities, pectins carinatum or excavatum-

Symptoms-
Ectopia lentis
Aortic disease
Arachnodactyly- joint hyper mobility
Tall stature
Berry aneurysms
High arched plate
Scoliosis
Long extremities

Question 20

α1-Antitrypsin in elastin degradation

Answer 20

Blood and other body fluids contain α1-antitrypsin which inhibits a number of proteolytic enzymes that hydrolyze and destroy proteins.
• AAT has the important physiologic role of inhibiting neutrophil elastase, a powerful protease that is released into the extracellular space and degrades elastin of alveolar walls as well as other structural proteins in a variety of tissues .
• Most of the AAT found in plasma is synthesized and secreted by the liver.

Question 21

α1-Antitrypsin in the lungs

Answer 21

In the normal lung, the alveoli are chronically exposed to low levels of neutrophil elastase released from activated and degenerating neutrophils. The proteolytic activity of elastase can destroy the elastin in alveolar walls if unopposed by the action of AAT, the most important inhibitor of neutrophil elastase . Because lung tissue cannot regenerate, the destruction of the connective tissue of alveolar walls caused by an imbalance between the protease and its inhibitor results in pulmonary disease.

Question 22

Emphysema

Answer 22

permanent dilatation of pulmonary air spaces distal to the terminal bronchioles, caused by the destruction of the alveolar walls and the pulmonary capillaries required for gas exchange

Centriacinar- associated with smoking
Paracinar- associated with alpha 1 antitrypisin