Flashcards in The Genetic Code, Mutations and Traslation Deck (20):
Beta-thalassemia, Gaucher disease and Tay-Sachs are common examples of what type of mutation?
Mutation in splice sites
Named 3 examples at least of triplet repeat expansion diseases, what differentiate them?
*Huntington disease, spinobulbar muscular atrophy - mutation in coding region
*Fragile X syndrome, myotonic dystrophy - mutation in non-coding region
What triplet and then amino acid is expanded in repetition in Huntington disease?
CAG triplet (30 to 60 repeats, normal allele 5 tandem repeat)
Glutamine - long Gln tract extremely unstable protein
What type of mutation cause alfa-thalassemia and Cri-duchat?
Large segment deletions
*deleted one or more alfa-globin genes in chromosome 16
*terminal deletion of short arm of chromosome 5
What step do pseudomonas and Diphteria toxins block during translation in eukaryotic? How do they make it?
Translocation. By inactivation of elongation factor-2 (eEF2) through ADP-ribosylation.
What cause the gray baby syndrome?
Chloramphenicol - give to newborn (especially premature)
*not enough UDP-glucuronyl transferase to excrete the drug.
What combination of drugs can precipitate and cause ototoxicity and nephrotoxicity?
Aminoglucosydes with loop diuretic
What is the cause of cystic fibrosis?
Chloride channel protein (CFTR) abnormally fold and not correct posttranslational processing of oligosaccharides side chains ➡️ degraded in proteasome.
*by deletion of phe in 508 position
What are the signals that indicate the correct fate of the proteins?
- N-terminal hydrophobic signal - RER
*secreted - insulin
*cell membrane - Na/K ATPase
*ultimately direct to lysosome - sphingomyelinase and lysosomal hydrolases by;
- Phosphorylation of mannose - lysosomes
Main organ compromised in Alfa 1-antitrypsin deficiency? Why does it happen?
Liver - cirrhosis.
*Z mutation [ZZ] (more than 90 variations, Z and S most common) - misfold of Alfa 1-antitrypsin - aggregate in RER ➡️ damage cells.
Lysosomal enzymes released into extracellular space, inclusion bodies inside cell ➡️ (child 5 mo age example), "gargoyle face", gingival hyperplasia, macroglosia, joint immobility, clubfoot, claw-hand, scoliosis, psychomotor retardation, growth retardation, mitral valve defect, cardio respiratory failure, bone fracture and deformities, ⬇️ lysosome enzyme within cells but ⬆️ extracellular fluid and blood, numerous intracellular inclusions; what is the disease and why happen?
I cell disease - genetic defect affects phosphorylation of mannose
What does Prenylation allow?
Interaction of a Protein with cell membrane - anchored proteins
*add covalently a farnesyl or geranylgeranyl (hydrophobic isoprene polymers, lipids) to the protein via thioether linkages at cysteine residues near the C terminal of the protein
What may be the cause if an anchor protein is not associated with the membrane?
Prenylation site may be mutated
*CAAX box is the most common prenylation site in proteins
What amino acid is unique to collagen?
What do proline and lysil hydroxilases (most prolyl hidroxylase) need to hydroxylate them? What happen if there is a deficiency of that?
Ascorbate - vitamin C ▶️ deficiency ▶️ scurvy
What enzyme assemble collagen molecules into fibrils? What does it need, and what happen if there isn't?
Cross-link by lysyl oxidase - need O2 and copper
- copper deficiency ▶️ Menkes disease
What causes copper deficiency in Menkes disease (Ehlers-Danlos syndrome type IX, Kinky hair syndrome?
Mutation in gene ATP7A ▶️ ATP-dependent copper efflux protein in intestine ➡️ copper stay in intestine, not go to bloodstream
What can cause low ceruloplasmin levels?
All situations that can cause low copper blood levels; some:
- Menkes disease
- Wilson disease (ATP7B mutation)
Or aceruloplasminemia - low gene expression
What causes the different types of Ehlers-Danlos Syndromes? What type of collagen is altered in type IV ED syndrome (vascular type)? Why?
* Type III Collagen - mutation gene for type 3 procollagen