4. The Genetic Code, Mutations, and Translation Flashcards Preview

Biochemistry > 4. The Genetic Code, Mutations, and Translation > Flashcards

Flashcards in 4. The Genetic Code, Mutations, and Translation Deck (64):
1

How many codons exist?

64

2

Stop codons

UAA, UGA, UAG

3

Start codon + amino acid

AUG, methionine (met in prokaryotes)

4

Code is unambiguous

1 codon = 1 amino acid

5

Code is degenerate, 2 exceptions

1 amino acid > 1 codon
Exceptions: Met and tryptophan (Trp)

6

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)

7

Missense mutation

New codon specifies different amino acid, variable effects

8

Nonsense mutation

Stop codon

9

Large segment deletions

Often during unequal crossover in meiosis

10

Recombination crossover when?
Examples of unequal crossover (2)

Normal in Meiosis I
Examples:
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

11

Examples (3) of splice site mutations

Beta-thalassemia, Gaucher disease, Tay-Sachs

12

Beta-thalassemia
- Disease
- Characteristics
- Treatment

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

13

Huntington disease
- Type of disorder, age of onset
- Symptoms
- Normal vs diseased repeats
- Amino acid involved
- Juvenile

- 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

14

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)

15

Amino acid activation by..
Energy required from..

Aminoacyl tRNA synthetase (self-checking function)
Two high-energy bonds from ATP

16

Amino acid location on tRNA

3' end

17

Amino acid linked to tRNA is a..

High energy bond, energy for peptide bond linking later

18

Formation of peptide bond between..

Carboxyl group (C) of growing peptide and amino group (NH3) of new amino acid

19

Where does translation occur?

In cytoplasm

20

Three stages of protein synthesis

Initiation, elongation and termination

21

What binds to mRNA during translation?

Small ribosomal subunit
- Prokaryotes = 16S to Shine Dalgarno sequence in 5' UTR
- Eukaryotes = binds to 5' cap

22

What happens after small subunit binds to mRNA?

(f)Met tRNA binds to AUG and large subunit binds to small subunit

23

What is P-site?

Peptidyl site: binding site for growing peptide chain

24

What is A-site?

Aminoacyl site: new incoming tRNA molecule

25

What are the three steps of elongation?
Energy required?

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

26

How do Pseudomonas and Diptheria toxins inhibit protein synthesis?

ADP-ribosylation of elongation factor-2 (used in translocation) in eukaryotes

27

How do Shiga and Shiga-like toxins stop protein synthesis?

Clip adenine residue from 28S rRNA in the 60S subunit

28

Termination (2 steps)

1. Stop codon in A-site
2. Peptide transferase (+ release factors) hydrolyze the protein from final tRNA in P site

29

Polysome

Several ribosomes on 1 mRNA

30

Inhibitors of prokaryotic translation

Streptomycin, erythromycin, tetracyclin, chloramphenicol (also inhibits mitochondrial translation, because it resembles prokaryotic ribnosomes)

31

Inhibitor of eukaryotic translation

Cycloheximide, Diphteria, Pseudomonas toxins

32

Gray baby syndrome: drug, problem, symptoms

Chloramphenicol
UDP-glucuronyl transferase activity is insufficient (excretion)
Cyanosis, low blood pressure, death

33

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

34

Proteins translated on RER ribosomes (3)

Secreted proteins
Proteins inserted into cell membrane
Lysosomal proteins

35

Assistance in protein folding by..

Chaperones

36

Incorrect folding:
- Marked by
- Where destructed?

- Multiple copies of ubiquitin
- Proteasomes -> cytoplasmic complex, multiple proteases, play a role in producing antigenic peptides

37

Cystic fibrosis
- Genetic defect?
- Abnormal protein?

- Deletion Phe from 508, improper folding and post translational processing
- Abnormal chloride channel protein is degraded

38

Signal for RER translation

N-terminal hydrophobic signal (cleaved off in ER)

39

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

40

Glycoproteins are created in

ER and Golgi, proteins acquire oligosaccharide side chains

41

N-glycosylation
What does it require?
Where?

Sugar chains to nitrogen of asparagine residues, requires dolichol phosphate
ER and Golgi

42

O-glycosylation
Where?

Sugar chains to hydroxyl group of serine or threonine residues
Only in Golgi

43

Alfa1-antitrypsin deficiency
- Synthesized by
- Normal function
- Allelic variants associated with deficiency, type of mutation

- Liver
- Inhibits proteases released during inflammation
- Z and S, point mutations

44

I-cell disease
- 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

45

Glycosylation

Addition of oligosaccharide (ER, Golgi)

46

Proteolysis

Cleavage of peptide bonds
Proinsulin, trypsinogen, prothrombin

47

Phosphorylation

Addition of phosphate by protein kinases

48

Gamma-carboxylation

Produces Ca2+ binding sites

49

Prenylation

Addition of farnesyl or geranylgeranyl lipid groups to membrane-associated proteins

50

Collagen structure

Gly-X-Y-Gly-X-Y

51

Unique amino acid of collagen + how produced

Hydroxyproline
Hydroxylation propel residues Y positions in pro collagen

52

Pro-alfa chains made by:

Prepro-alfa chain + cleaved hydrophobic signal

53

Which vitamin is required for hydroxylation of prolines and lysines by propyl and lysyl hydroxylases?

Vitamin C (Ascorbate)

54

Procollagen formation

Three pro-alfa chains, transferred to Golgi

55

Tropocollagen

Procollagen secreted from cell, ends are cleaved by proteases

56

Cross linking of collagen molecules
What does it require?

Fibrils, involves lysyl oxidase
Required O2 and copper

57

Collagen type 1

High tensile strength
Bone, skin, tendons
Osteogenesis imperfecta, Ehlers-Danlos

58

Collagen type 2

Thin fibrils, structural
Cartilage, vitreous humor

59

Collagen type 3

Thin fibrils, pliable
Blood vessels, granulation tissue
Ehlers-Danlos IV, Keloid

60

Collagen type 4

Amorphous (=lacking clear structure)
Basement membranes
Goodpasture, Alport disease, Epidermolysis bullosa

61

Scurvy
- Defect
- Major symptoms (6)

- Deficient hydroxylation due to ascorbate deficiency
- Petechiae, ecchymoses, loose teeth, bleeding gums, poor wound healing, poor bone development

62

Osteogenesis imperfecta
- Defect
- Major symptoms (3)

- Mutation in collagen genes
- Skeletal deformities, fractures, blue sclera

63

Ehlers-Danlos syndromes
- Defect
- Major symptoms (6)

- Mutations in collagen genes and proline and lysyl hydroxylases
- Hyperextensible, fragile skin, hypermobile joints, dislocations, varicose veins, ecchymoses, arterial, intestinal ruptures

64

Menkes diseases
- Defect
- Type of genetic defect
- Major symptoms (6)

- Deficient cross linking due to copper deficiency
- X-linked recessive, ATP7A (ATP dependent copper efflux protein in intestine)
- Depigmented (steely) hair, arterial turtuosity and rupture, cerebral degeneration, osteoporosis, anemia