Chapter 4: The Genetic Code, Mutations and Translation (continued)

Question 1

Describe the covalent modification: proteolysis?

Answer 1

cleavage of peptide bonds to remodel proteins and activate them (proinsulin, trypsinogen, prothrombin)

Question 2

How does phosphorylation of proteins take place?

Answer 2

addition of phosphate by protein kinases

Question 3

Describe the covalent modification: γ-carboxylation importance is producing coagulation factors?

Answer 3

introduces Ca2+ binding sites

Question 4

Describe the covalent modification: prenylation?

Answer 4

addition of farnesyl or geranylgeranyl lipid groups to certain membrane associated proteins

Question 5

Does collagen go through several posttranslational modification steps or co-translational modification steps?

Answer 5

both co- and posttranslational modifications

Question 6

What is the repeated tripeptides sequence in collagen formation?

Answer 6

Gly- X- Y- Gly -X- Y etc.

Question 7

How is hydroxyproline produced?

Answer 7

by hydroxylation of prolyl residues at the Y positions in procollagen chains as they pass through the RER

Question 8

Describe the steps in collagen synthesis?

Answer 8

1. prepro- α chains containing a hydrophobic signal sequence are synthesized by ribosomes attached to the RER
2. the hydrophobic signal sequence is removed by signal peptidase to form pro-α chains
3. Selected prolines and lysines are hydroxylated by prolyl and lysl hydroxylases. These enzymes located in the RER, require ascorbate (vitamin C)
4. Selected hydroxylysines are glycoslylated
5. Three pro-α chains assemble to form a triple helical strucutre (procollagen) which can now be transferred to the Golgi. Modification of oligosaccharide continues in the Golgi
6. procollagen is secreted from the cell
7. the propeptides are cleaved from the ends of procollagen by proteases to form collagen molecules (also called tropocollagen)
8. collagen molecules assemble into fibrils. Cross-linking involves lysl oxidase, an enzyme that requires O2 and copper
9. Fibrils aggregate and cross-link to form collagen fibers

Question 9

What are the characteristics of collagen type I?

Answer 9

bundles of fibers

high tensile strength

Question 10

What are the charactertistics of collagen type II?

Answer 10

thin fibrils

structural

Question 11

What are the characteristics of collagen type III?

Answer 11

thin fibrils

pliable

Question 12

What are the characteristics of collagen type IV?

Answer 12

amorphous

Question 13

What is the tissue distribution of collagen type I?

Answer 13

bone, skin, tendons

Question 14

What is the tissue distribution of collagen type II?

Answer 14

cartilage, vitreous humor

Question 15

What is the tissue distribution of collagen Type III?

Answer 15

blood vessels, granulation tissue

Question 16

What is the tissue distribution of collagen Type IV?

Answer 16

basement membranes

Question 17

Associated disease of Col Type I?

Answer 17

OI
Ehlers Danlos

Question 18

Associated diseases to Col Type III?

Answer 18

Ehlers Danlos
Type IV
Keloid formation

Question 19

Associated diseases to Col Type IV?

Answer 19

Goodpasture Syndrome
Alport Disease

Question 20

What are some clinical features of ED? (Name 4)

Answer 20

thick translucent skin; arterial, intestinal, or uterine rupture; and easy bruising, hyperextensible, hypermobile joints, dislocations, varicose veins

Question 21

What is the exact defect in Ehlers Danlos?

Answer 21

mutations in collagen genes and proline and lysyl hydroxylases

Question 22

Clinical features of Menkes disease?

Answer 22

depigmented (steely) hair, arterial tortuosity, rupture cerebral degeneration, osteoporosis, anemia

Question 23

What is the genetic basis for Menkes disease?

Answer 23

deficient cross-linking secondary to functional coppers deficiency

Question 24

Other names for Menke’s disease?

Answer 24

Ehlers-Danlos syndrome type IX (kinky hair syndrome)

Question 25

What gene is responsible for Menkes?

Answer 25

gene causing mutations in the gene ATP7A which encodes an ATP-dependent copper efflux protein in the intestine

copper can be absorbed into the mucosal cell but it cannot be transported into the bloodstream

consequently patients have severe copper deficiency, and all copper-requiring enzymes will be adversely affected

all copper requiring enzymes like lysyl oxidase which plays a direct role in collagen formation will be affected

Question 26

What is the meaning of the genetic code being unambiguous?

Answer 26

1 codon = 1 amino acid

Question 27

What is the meaning of the genetic code being redundant?

Answer 27

1 amino acid > 1 codon