Unit 1 Flashcards
1
Q
Free energy equations?
A
delta G = delta G knot + RT lnKeq
2
Q
Forward direction when?
A
Keq >1
3
Q
2 types of high energy bonds? Ex?
A
- ) Thioester (C-S) = Acetyl CoA
- ) Phosphate bonds
- Phosphoanhydride = ATP (P-O-P)
- (P-N) = phosphocreatine
- (C-O-P) = phosphophenolpyruvate
4
Q
Diseases related to insoluble purines?
A
- ) Gout
2. ) Lesch-Nyhan
5
Q
Methylation
A
Often happens with C-G, but can be dangerous because it is inversely related to transcription level
6
Q
Deamination
A
C to U = usually caught
5-methylcytosine to T = not good
7
Q
Regulatory RNA
A
miRNA
siRNA = down regulate gene expression
8
Q
Stabilize single single strands of fork during replication?
A
- SSBP’s - single stranded binding proteins
9
Q
Diseases from mutations in DNA repair machinery?
A
Cockanyes and XP
10
Q
What fixes bulky chemical adducts?
A
NER
11
Q
What fixes uracil in DNA?
A
BER - No distortion of DNA
12
Q
MMR: Recognized when? By what proteins?
A
Shortly after DNA synthesis; MLH (MutL proteins)
13
Q
Double breaks fixed by? (2)
A
- HR (homologous recombination)
- NHEJ (non-homologous end joining)
14
Q
Last case scenerio if Pol 3 can’t move?
A
Damage bypass/tolerance
15
Q
TFIID function?
TFIIH function?
A
- Binds to TATA box
- Facilitates NER repair, adds PO4 to C terminal of Pol II, acts as helicase
16
Q
Diseases related to mutations of TFIIH?
A
XD, Cockanyes, trycothiodystrophy
17
Q
Area after 3’ UTR that contains the AAUAAA
A
Consensus sequences
18
Q
Functions of cap? (4)
A
- ) Resistant to exonucleases
- ) Cap binding complex helps with splicing
- ) eIF4E recognizes it for transport to ribosomes
- ) Decapping leads to degradation
19
Q
Reactions to make cap? (3)
A
- ) Cut off PO4
- ) Add backwards GTP
- ) Methlyate 7 position
20
Q
Splicing genetic disorders?
A
- ) Marfins
2. ) CD44 (cell-surface glycoprotein
21
Q
Example when alternative poly A sites are used for multiple proteins?
A
- IgM (membrane bound vs free immunoglobulins)
22
Q
Cis acting elements?
A
- TATA, promoters, enahncers
23
Q
Diseases that arise from mutations in DNA control elements?
A
- ) Thallessemias - b-globin mutation in promoter sequence, Locus control region
- ) Hemophelia B- Leyden - Factor IX gene,
- ) Fragile X - CGG repeat that is methylated and under transcribed
24
Q
2 classes of activators / repressors?
A
- ) Cofactors
2. ) Sequence specific DNA binding proteins
25
4 major families of SSDBP's?
| - Mutations related to each one?
1. ) Homeodomain - Craniosynostosis
2. ) Zinc Finger - AIS
3. ) bZIP -
4. ) HLH - Waardenburg type II
26
2 chromatin remodeling factors?
1. ) ATP dependent SWI/SNF
| 2. ) Modify Histones via N tails that are rich in Lysine
27
HATS vs. HDACS
```
HATS = coactivators
HDATS = corepsressors
```
28
Diseases related to histone acetylation alteration? (2)
1. )Rubenstein-Taybi = Mutation in 1 copy of CREB binding protein
2. ) Leukemia = Fusion of HATS / HDACS
29
How do activators/repressors modulate transcription?
1. ) Interact with TF's
| 2. ) Interact with chromatin that allows accesibilty
30
Ways sequence specific binding proteins are regulated?
1.) Binding a ligand: Steroid hormones bind to Zn finger TF's that recruit HATS; ex = Tamoxifin
2.) Regulate entry: NFkB bound to IkB = no inflamm. response (Aspirin does this)
Calcineurin dephosphorylates NF-ATc which leads to inflammatory response
3.) Regulate amount of TF: WNT activates APC which phosphorylates B-Catenin; No APC = Increased B-Catenin and increased polyps
Increased MDM2 = decreased P53
4. ) Regulate binding in DNA = E and Id protein home and heterodimers of Basic HLH
5. ) Phos. of CREB = CREB-P = increased transcription by recruiting HATS (CBP/Pol II)
31
Importance of eIF 4E in translation?
- Binds 7 methyl guanosine of the cap
32
Importance of IRES?
- Allows transcription without a CAP
33
Importance of eIF2 alpha?
When phosphorylated it can block translation which is often accomplished using interferons
34
Rapamycin does what?
Cancer treatment drug that phospohorylates 4E-BP down regulating translation
35
- Ferretin vs. transferrin?
Ferretin binds iron and transferrin sequesters iron
36
Common post translational covalent modifications? (6)
1.) Hydroxyl group to proline
2.) Carboxylation of glutamate
3.) Glycosylation: O = Ser, Thr
N = Asparagine
- CDG-a1 if this doesn't happen
4.) Acetylation and methylation of of lysine and argenine for DNA-histone interactions
5.) Reverse phosphorylation/dephosphorylation of hydroxyl groups on Ser, Thr, and Tyr which are important for signal transduction pathways
6.) Ubiquitization - add AA to Lyseine to be degraded by proteosomes
37
Most frequently found AA's in turns and loops?
- Glycine and proline
38
Two major classes of chaperones?
1. ) HSP 70 = Binds to hydrophobic areas to allow folding
| 2. ) GroEl - same but don't need heat shcok
39
Approaches to purifying a protein (7)
1. ) Gel filtration chromotography --> Seperated based on size
2. ) Ion exchange chromotography --> based on charge
3. ) Affinity chromotography --> based on ligand interactions
4. ) SDS Page --> purity
5. ) Mass spec --> mass of the protein
6. ) N-terminal sequence --> Edmans degradation
7. ) Western --> identified using antibodies
40
Alzheimers:
- Progression of disease?
- AB42 coded on what gene?
- Problem arrises when?
- How can genetics play a role?
- Best treatment option?
- Current drug used? Does what?
- Plaque - tangles
- Comes from chromosome 21
- B secretase followed by gamma secreatase that cleaves two units longer
- ApoE e4 = increase risk of disease
- Decrease Beta secratase
- Donepezil = compensates for neuronal disfunction
41
Types of Prion disease?
- Infection --> vCFJ and canabilism
- Sporadic --> Alpha helices - beta sheets
- Inheritied --> Mutation in prion gene
42
- Restriction endonucleases are often what?
- Palindromic
43
- PCR amplifiactions often used for what?
- Diagnosing genetic alterations
44
Compare and contrast DNA sequencing with PCR amplification? Goal of each?
Similarities: Both use primer sequences to initiate replication of genes
Differences: PCR uses double stranded DNA and sequencing uses single. Sequencing uses ddNTP's so there isn't a 3'hydroxyl
Goals: PCR = Amplify a given DNA fragment
Sequencing = Determine sequence of fragment
45
- What are enzymes? What do they do?
Protein catalysts --> increase rate of a reaction by decreasing the activation energy
46
- Chemistry that helps enzymes work? (3)
1. ) Covalent chemistry
2. ) Metal ion --> ions position the substrate
3. ) General acid-base --> Amino acid side chains donate or accept protons
47
- Km
- Kcat
- Enzyme efficiency
- Substrate necessary to reach 1/2 vmax
- Turnover number when the enzyme is saturated
- Kcat (speed) / Km (how much is needed)
48
- Types of inhibition and their effects?
1. ) Competitive = Binds to E and increases Km
2. ) Uncompetitive = Binds to ES and decrease Vmax and changes apparent Km
3. ) Mixed = binds outside of active site to either ES or E; both Vmax and Km affected
4. ) Noncompetitive (mixed) = reduces activity but don't effect substrate binding
49
Enzyme regulation mechanisms: (4)
1. ) Allosteric = binding of 1 molecule changes conformation
2. ) Covalent = Phophorylation type deals
3. ) Binding of a regulatory protein = Similar to allosteric but with peptide
4. ) Proteolytic cleavage = Cleavge makes them active
50
Inflammatory Bowel Disease:
- Smokers at greater risk of?
- Former and nonsmokers at greater risk of?
- IBD's extraintestinal manifestations?
- Rising prevalence related to?
Crohns vs. Ulcerative Colitis:
- Area affacted?
- Continuity?
- Type of inflammation?
- Bloody stool (hematochezia)?
- Fistula's?
- Upper GI?
- Crohns
- Ulcerative Colitis
- Lots of itis stuff
- Diet, antibiotics, tobacco
Crohns:
- Ileum
- Discontinuous
- Transmural
- Rare
- Common
- Often affected
Crohns:
- Rectum
- Continuous
- Mucosal
- Common
- Rare
- Not affected
