Chapter 4: The Genetic Code, Mutations and Translation (continued) Flashcards
Describe the covalent modification: proteolysis?
cleavage of peptide bonds to remodel proteins and activate them (proinsulin, trypsinogen, prothrombin)
How does phosphorylation of proteins take place?
addition of phosphate by protein kinases
Describe the covalent modification: γ-carboxylation importance is producing coagulation factors?
introduces Ca2+ binding sites
Describe the covalent modification: prenylation?
addition of farnesyl or geranylgeranyl lipid groups to certain membrane associated proteins
Does collagen go through several posttranslational modification steps or co-translational modification steps?
both co- and posttranslational modifications
What is the repeated tripeptides sequence in collagen formation?
Gly- X- Y- Gly -X- Y etc.
How is hydroxyproline produced?
by hydroxylation of prolyl residues at the Y positions in procollagen chains as they pass through the RER
Describe the steps in collagen synthesis?
- prepro- α chains containing a hydrophobic signal sequence are synthesized by ribosomes attached to the RER
- the hydrophobic signal sequence is removed by signal peptidase to form pro-α chains
- Selected prolines and lysines are hydroxylated by prolyl and lysl hydroxylases. These enzymes located in the RER, require ascorbate (vitamin C)
- Selected hydroxylysines are glycoslylated
- 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
- procollagen is secreted from the cell
- the propeptides are cleaved from the ends of procollagen by proteases to form collagen molecules (also called tropocollagen)
- collagen molecules assemble into fibrils. Cross-linking involves lysl oxidase, an enzyme that requires O2 and copper
- Fibrils aggregate and cross-link to form collagen fibers
What are the characteristics of collagen type I?
bundles of fibers
high tensile strength
What are the charactertistics of collagen type II?
thin fibrils
structural
What are the characteristics of collagen type III?
thin fibrils
pliable
What are the characteristics of collagen type IV?
amorphous
What is the tissue distribution of collagen type I?
bone, skin, tendons, scar tissue
What is the tissue distribution of collagen type II?
cartilage, vitreous humor
What is the tissue distribution of collagen Type III?
blood vessels, granulation tissue
What is the tissue distribution of collagen Type IV?
basement membranes
Associated disease of Col Type I?
OI
Ehlers Danlos
Associated diseases to Col Type III?
Ehlers Danlos
Type IV
Keloid formation
Associated diseases to Col Type IV?
Goodpasture Syndrome
Alport Disease
What are some clinical features of ED? (Name 4)
thick translucent skin; arterial, intestinal, or uterine rupture; and easy bruising, hyperextensible, hypermobile joints, dislocations, varicose veins
What is the exact defect in Ehlers Danlos?
mutations in collagen genes and proline and lysyl hydroxylases
Clinical features of Menkes disease?
depigmented (steely) hair, arterial tortuosity, rupture cerebral degeneration, osteoporosis, anemia
What is the genetic basis for Menkes disease?
deficient cross-linking secondary to functional coppers deficiency
Other names for Menke’s disease?
Ehlers-Danlos syndrome type IX (kinky hair syndrome)
What gene is responsible for Menkes?
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
What is the meaning of the genetic code being unambiguous?
1 codon = 1 amino acid
What is the meaning of the genetic code being redundant?
1 amino acid > 1 codon
