Flashcards in 4. The Genetic Code, Mutations, and Translation Deck (64):
How many codons exist?
UAA, UGA, UAG
Start codon + amino acid
AUG, methionine (met in prokaryotes)
Code is unambiguous
1 codon = 1 amino acid
Code is degenerate, 2 exceptions
1 amino acid > 1 codon
Exceptions: Met and tryptophan (Trp)
Point mutations: transition and transversion
Transition: purine-pyrimidine bp -> purine-pyrimidine bp (AT->GC)
Transversion: purine-pyrimidine bp -> pyrimidine-purine bp (AT->TA or CG)
New codon specifies different amino acid, variable effects
Large segment deletions
Often during unequal crossover in meiosis
Recombination crossover when?
Examples of unequal crossover (2)
Normal in Meiosis I
1. alfa-thalassemia (deletion of one or more alfa-globin genes from chromosome 16)
2. Cri-du-chat (mental retardation, microcephaly, wide-set eyes, kitten like cry), terminal deletion short arm chromosome 5
Examples (3) of splice site mutations
Beta-thalassemia, Gaucher disease, Tay-Sachs
Many different types of mutations, deficiency of beta-globin compared to alfa-globin.
Mediterranean areas, splenomegaly, bone deformities (excessive activity bone marrow). Treatment: blood transfusions every 2-3 weeks, cave iron overload
- Type of disorder, age of onset
- Normal vs diseased repeats
- Amino acid involved
- Autosomal dominant, 43-48
- Mood disturbance, impaired memory, hyperreflexia, abnormal gait, chorea, dystonia, dementia, dysphagia
- 5 vs >30
- Glutamine (CAG)
- Juvenile often paternal allele inherited
Trinucleotide repeat expansion diseases
- 2 in coding region
- 2 in untranslated region
- Huntington (CAG), Spinobulbar muscular atrophy (CAG)
- Fragile X (CGG), Myotonic dystrophy (CTG), Friedreich's ataxia (GAA)
Amino acid activation by..
Energy required from..
Aminoacyl tRNA synthetase (self-checking function)
Two high-energy bonds from ATP
Amino acid location on tRNA
Amino acid linked to tRNA is a..
High energy bond, energy for peptide bond linking later
Formation of peptide bond between..
Carboxyl group (C) of growing peptide and amino group (NH3) of new amino acid
Where does translation occur?
Three stages of protein synthesis
Initiation, elongation and termination
What binds to mRNA during translation?
Small ribosomal subunit
- Prokaryotes = 16S to Shine Dalgarno sequence in 5' UTR
- Eukaryotes = binds to 5' cap
What happens after small subunit binds to mRNA?
(f)Met tRNA binds to AUG and large subunit binds to small subunit
What is P-site?
Peptidyl site: binding site for growing peptide chain
What is A-site?
Aminoacyl site: new incoming tRNA molecule
What are the three steps of elongation?
1. Charged tRNA binds to A-site
2. Peptidyl transferase (large subunit) forms peptide bond + break of bond to P-site
3. Translocation: ribosome moves 3 nucleotides
Energy: high energy bonds from tRNA-aminoacid (2) + GTP (2), in total 4
How do Pseudomonas and Diptheria toxins inhibit protein synthesis?
ADP-ribosylation of elongation factor-2 (used in translocation) in eukaryotes
How do Shiga and Shiga-like toxins stop protein synthesis?
Clip adenine residue from 28S rRNA in the 60S subunit
Termination (2 steps)
1. Stop codon in A-site
2. Peptide transferase (+ release factors) hydrolyze the protein from final tRNA in P site
Several ribosomes on 1 mRNA
Inhibitors of prokaryotic translation
Streptomycin, erythromycin, tetracyclin, chloramphenicol (also inhibits mitochondrial translation, because it resembles prokaryotic ribnosomes)
Inhibitor of eukaryotic translation
Cycloheximide, Diphteria, Pseudomonas toxins
Gray baby syndrome: drug, problem, symptoms
UDP-glucuronyl transferase activity is insufficient (excretion)
Cyanosis, low blood pressure, death
Characteristics of the four protein shapes
Primary: amino acid sequence
Secondary: alfa-helix, beta-pleated sheets (hydrogen bonds)
Tertiary: hydrogen, hydrophobic and ionic bonds, sometimes strong covalent disulfide bonds.
Quaternary: subunits interaction
Proteins translated on RER ribosomes (3)
Proteins inserted into cell membrane
Assistance in protein folding by..
- Marked by
- Where destructed?
- Multiple copies of ubiquitin
- Proteasomes -> cytoplasmic complex, multiple proteases, play a role in producing antigenic peptides
- Genetic defect?
- Abnormal protein?
- Deletion Phe from 508, improper folding and post translational processing
- Abnormal chloride channel protein is degraded
Signal for RER translation
N-terminal hydrophobic signal (cleaved off in ER)
Signal for directing protein to lysosome
- If defect, what disease?
Phosphorylation of mannose residues in N-linked oligosaccharide chains (by N-acetyl-glucosamine-1 phosphotransferase) -> Mannose-6-phosphate
- I-cell disease, lysosomal enzymes released in extracellular space, inclusion bodies accumulate in cell
Glycoproteins are created in
ER and Golgi, proteins acquire oligosaccharide side chains
What does it require?
Sugar chains to nitrogen of asparagine residues, requires dolichol phosphate
ER and Golgi
Sugar chains to hydroxyl group of serine or threonine residues
Only in Golgi
- Synthesized by
- Normal function
- Allelic variants associated with deficiency, type of mutation
- Inhibits proteases released during inflammation
- Z and S, point mutations
- Symptoms (4)
- Prognosis (1)
- Diagnostics (1)
S. Coarse facial features, gingival hyperplasia, macroglossia
S. Joint immobility, clubfoot, claw-hand, scoliosis, growth retardation, bone fracture and deformities
S. Psychomotor retardation
S. Cardiorespiratory failure, mitral valve defect
P. Death in first decade
D. Secretion of active lysosomal enzymes into blood and extracellular fluid
Addition of oligosaccharide (ER, Golgi)
Cleavage of peptide bonds
Proinsulin, trypsinogen, prothrombin
Addition of phosphate by protein kinases
Produces Ca2+ binding sites
Addition of farnesyl or geranylgeranyl lipid groups to membrane-associated proteins
Unique amino acid of collagen + how produced
Hydroxylation propel residues Y positions in pro collagen
Pro-alfa chains made by:
Prepro-alfa chain + cleaved hydrophobic signal
Which vitamin is required for hydroxylation of prolines and lysines by propyl and lysyl hydroxylases?
Vitamin C (Ascorbate)
Three pro-alfa chains, transferred to Golgi
Procollagen secreted from cell, ends are cleaved by proteases
Cross linking of collagen molecules
What does it require?
Fibrils, involves lysyl oxidase
Required O2 and copper
Collagen type 1
High tensile strength
Bone, skin, tendons
Osteogenesis imperfecta, Ehlers-Danlos
Collagen type 2
Thin fibrils, structural
Cartilage, vitreous humor
Collagen type 3
Thin fibrils, pliable
Blood vessels, granulation tissue
Ehlers-Danlos IV, Keloid
Collagen type 4
Amorphous (=lacking clear structure)
Goodpasture, Alport disease, Epidermolysis bullosa
- Major symptoms (6)
- Deficient hydroxylation due to ascorbate deficiency
- Petechiae, ecchymoses, loose teeth, bleeding gums, poor wound healing, poor bone development
- Major symptoms (3)
- Mutation in collagen genes
- Skeletal deformities, fractures, blue sclera
- Major symptoms (6)
- Mutations in collagen genes and proline and lysyl hydroxylases
- Hyperextensible, fragile skin, hypermobile joints, dislocations, varicose veins, ecchymoses, arterial, intestinal ruptures