Biochem - Cellular (Collagen synthesis, structure, & conditions)

Question 1

What is the most abundant protein in the human body?

Answer 1

Collagen

Question 2

Briefly describe the modification of collagen.

Answer 2

Extensively modified by posttranslational modification

Question 3

What is the function of collagen?

Answer 3

Organizes and strengthens extracellular matrix

Question 4

What are the types of collagen? Where is each mainly found?

Answer 4

(1) Type I - Bone, Skin, Tendon (2) Type II - Cartilage (including hyaline) (3) Type III - Reticulin (4) Type IV - Basement membrane; Think: “Be (So Totally) Cool, Read Books”

Question 5

What is the most common type of collagen? What percentage of collagen is this type?

Answer 5

Type I - Most common (90%)

Question 6

Where/In what context(s) is Type I collagen found (give 7)?

Answer 6

Bone (made by osteoblasts), Skin, Tendon, dentin, fascia, cornea, late wound repair; Think: “type I: bONE”

Question 7

In what condition is production of type I collagen decreased?

Answer 7

Decreased production in osteogenesis imperfecta type I

Question 8

Where is Type II collagen found (give 3)?

Answer 8

Cartilage (including hyaline), vitreous body, nucleus pulposus; Think: “type II: carTWOlage”

Question 9

Where is Type III collagen found (give major category & 5 examples)?

Answer 9

Reticulin - skin, blood vessels, uterus, fetal tissue, granulation tissue

Question 10

In what condition is Type III collagen deficient?

Answer 10

Type III: deficient in the uncommon, VASCULAR type of Ehlers-Danlos syndrome (Think: “ThreE D”)

Question 11

Where is Type IV collagen found (give 3)?

Answer 11

Basement membrane, basal lamina, lens; Think: “type IV: under the FLOOR (basement membrane)

Question 12

In what condition is Type IV collagen defective?

Answer 12

Defective in Alport syndrome

Question 13

In what condition is Type IV collagen targeted by autoantibodies?

Answer 13

Targeted by autoantibodies in Goodpasture syndrome

Question 14

Where does collagen synthesis occur? What is the mechanism and amino acids involved?

Answer 14

Synthesis (RER); Translation of collagen alpha chains (preprocollagen) - usually Gly-X-Y (X and Y are proline or lysine).

Question 15

What amino acid content best reflects collagen synthesis, and why?

Answer 15

Glycine content best reflects collagen synthesis (collagen is 1/3 glycine)

Question 16

Where does collagen hydroxylation occur? What occurs during this?

Answer 16

Hydroxylation (RER); Hydroxylation of specific proline and lysine residues (requires vitamin C; deficiency –> scurvy)

Question 17

What is required for hydroxylation of collagen? What condition results from deficiency of this?

Answer 17

Hydroxylation of specific proline and lysine residues (requires vitamin C; deficiency –> scurvy)

Question 18

Where does glycosylation of collagen occur? What occurs during this?

Answer 18

Glycosylation (RER); Glycosylation of pro-alpha-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen alpha chains)

Question 19

What condition results from problems forming triple helix of collagen?

Answer 19

Problems forming triple helix –> osteogenesis imperfecta

Question 20

What occurs during exocytosis of collagen?

Answer 20

Exocytosis of procollagen into extracellular space

Question 21

What are 4 steps of collagen synthesis/modification that occur inside fibroblasts?

Answer 21

(1) Synthesis (RER) (2) Hydroxylation (RER) (3) Glycosylation (RER) (4) Exocytosis

Question 22

What occurs during proteolytic processing of collagen?

Answer 22

Cleavage of disulfide-rich terminal regions of procollagen, transforming it into insoluble tropocollagen.

Question 23

What occurs during cross-linking of collagen?

Answer 23

Reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (by Cu2+-containing lysyl oxidase) to make collagen fibrils

Question 24

What condition results from problems with cross-linking of collagen?

Answer 24

Problems with cross-linking –> Ehlers-Danlos

Question 25

What are 2 steps of collagen synthesis/modification that occur outside fibroblasts?

Answer 25

(1) Proteolytic processing (2) Cross-linking

Question 26

What is osteogensis imperfecta? What is another name for it? What causes it?

Answer 26

Genetic bone disorder (brittle bone disease) caused by a variety of gene defects

Question 27

What is the most common form of osteogenesis imperfecta? What is the phenotypic defect in this case?

Answer 27

Most common form is autosomal dominant with decreased production of otherwise normal type I collagen

Question 28

What are 4 manifestations of osteogenesis imperfecta?

Answer 28

OI manifestations can include: (1) Multiple fractures with minimal trauma; may occur during birth process (2) Blue sclerae due to translucency of the connective tissue over the choroidal veins (3) Hearing loss (abnormal ossicles) (4) Dental imperfections due to lack of dentin

Question 29

With what may osteogenesis imperfecta be confused?

Answer 29

May be confused with child abuse

Question 30

What skeletal findings may be seen in the x-ray of a child with osteogenesis imperfecta?

Answer 30

Severe skeletal deformity and limb shortening due to multiple fractures in a child

Question 31

What is Ehlers-Danlos syndrome? How does it present (3 symptoms)?

Answer 31

Faulty collagen synthesis causing hyperextensible skin, tendency to bleed (easy bruising), and hypermobile joints.

Question 32

How many types of Ehlers-Danlos syndrome exist? How do they vary? What are the options for inheritance?

Answer 32

6 + types. Inheritance and severity vary. Can be autosomal dominant or recessive.

Question 33

What are 3 conditions/outcomes with which Ehlers-Danlos syndrome can be associated?

Answer 33

May be associated with joint dislocation, berry and aortic aneurysms, organ rupture.

Question 34

What is the most common type of Ehlers-Danlos syndrome? What defines it?

Answer 34

Hypermobility type (joint instability): most common type

Question 35

What 2 symptoms are associated with classical type of Ehlers-Danlos syndrome? What causes it?

Answer 35

Classical type (joint and skin symptoms): caused by a mutation in type V collagen

Question 36

What 2 symptoms are associated with vascular type of Ehlers-Danlos syndrome? What causes it?

Answer 36

Vascular type (vascular and organ rupture): deficient type III collagen

Question 37

What is Menkes disease, and what causes it?

Answer 37

Connective tissue disease caused by impaired copper absorption and transport

Question 38

Menkes disease leads to decreased activity of what, and why?

Answer 38

Leads to decreased activity of lysyl oxidase (copper is a necessary cofactor)

Question 39

What are 3 symptoms associated with Menkes disease?

Answer 39

Results in brittle, "kinky" hair, growth retardation and hypotonia

Question 40

What is elastin? What are 6 locations in which it is found?

Answer 40

Stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect vertebrae --> relaxed and stretched conformations)

Question 41

What is the function ligamentum flava?

Answer 41

ligamenta flava (connect vertebrae --> relaxed and stretched conformations)

Question 42

In what 2 amino acids are elastin rich, and in what form are they?

Answer 42

Rich in proline and glycine, nonhydroxylated forms

Question 43

What forms scaffolding for tropoelastin?

Answer 43

Tropoelastin with fibrillin scaffolding

Question 44

What takes place to give elastin its elastic properties, and where does it occur?

Answer 44

Cross-linking takes place extracellularly and gives elastin its elastic properties

Question 45

What breaks down elastin? What normally inhibits this enzyme?

Answer 45

Broken down by elastase, which is normally inhibited by alpha1-antitrypsin

Question 46

What causes Marfan syndrome?

Answer 46

Marfan syndrome - caused by a defect in fibrillin, a glycoprotein that forms a sheath around elastin

Question 47

What deficiency causes Emphysema, and what results from this deficiency?

Answer 47

Emphysema - can be caused by alpha1-antitrypsin deficiency, resulting in excess elastase activity

Question 48

What causes wrinkles of aging?

Answer 48

Wrinkles of aging are due to decreased collagen and elastin production