LOs Flashcards
1
Q
Between C-G bonds and A-T bonds which one is stronger? Why?
A
C-G has three hydrogen bonds whereas A-T has two hydrogen bonds
2
Q
protein + nuclear DNA =
A
chromatin
3
Q
What are the DNA binding proteins involved in forming chromosomes?
A
histones and non-histone chromosomal proteins
4
Q
What is a name for chromatin that stains darkly throughout the cell cycle?
A
heterochromatin
5
Q
1) when do cells replicate heterochromatin? early or late?
2) is heterochromatin genetically active or inactive?
3) what part of the chromosome would you expect to find heterochromatin?
A
1) late replication
2) genetically inactive
3) centromere or telomere
6
Q
A gene is relocated from the center of the q arm to the very end of the arm. Would you see more or less expression from this gene? Why?
A
Gene will be silenced if relocated near heterochromatin which is found in centromere or telomere
7
Q
What keeps histone interaction with DNA loose by removing a positive charge? What effect will this have on transcription?
A
Histone acetylation
More transcription
8
Q
What keeps histone interaction with DNA loose by a physical interference? What effect will this have on transcription?
A
Histone methylation
More transcription
9
Q
How does the effect of histone methylation differ from the effect of DNA methylation?
A
Histone methylation increases transcription
Dan methylation silences transcription (epigenetic)
10
Q
What are the different interactions between histones and DNA?
A
142 hydrogen bonds between DNA and histone in each nucleosome
Hydrophobic interactions
Salt linkages- lys and arg (positive charges) effectively neutralize negatively charged DNA backbone
11
Q
Why would most changes/mutations to histones be lethal?
A
Histones are highly conserved
12
Q
What are the “beads” and the “string” in beads on a string?
A
beads = nucleosome core particle with DNA wound around histones string = DNA
13
Q
How many histone proteins are found in each nucleosome core?
A
8
14
Q
What percent of DNA sequence is in eons?
A
1.5%!!!!!!!!!!!!!!!!!
15
Q
What technology detects copy number variations? How does it work? What is the importance of CNVs?
A
CNVs are the basis for our differences and for disease states
Detect them with Comparative Genome Hybridization- probe human genome CHIP with DNA from one person and with DNA from normal reference and it detects CNV
16
Q
What is the function of DNA polymerase? What primer does it require?
A
Synthesizes DNA
Requires a free 3’-OH to begin
17
Q
What are the leading and lagging strands?
A
Leading is synthesized continuously
Lagging is synthesized in segments
18
Q
What direction does DNA polymerase synthesize DNA?
A
5’ to 3’ direction
19
Q
What is the function of helicase? What transcription factor has helicase capabilities?
A
Unwinds DNA
TFIIH
20
Q
What binds tightly and cooperatively to exposed single stranded DNA? Why is this necessary?
A
Single-stranded DNA binding proteins (SSBP)
Helps stabilize unwound DNA, prevents formation of hairpins, DNA bases remain exposed
21
Q
What relieves overwound DNA supercoils? What’s it called in bacteria? How does it work?
A
topoisomerase
in bacteria: DNA gyrate
Reversible enzyme that breaks a phosphodiester bond to change superhelicity
22
Q
What seals okazaki fragments?
A
DNA ligase
23
Q
What are the two types of spontaneous DNA damage?
A
Depurination and deamination
24
Q
What happens in depurination? What happens if it’s not repaired?
A
You lose the purine so there’s just a phosphate group and a deoxyribose
an A-T nucleotide pair is deleted
25
What happens in deamination? If it's not repaired what does it lead to?
C to U
| Base pair substitution from a G to A
26
Fake baking can lead to? How?
Pyrimidine dimers from UV radiation producing a covalent linkage between two adjacent pyrimidines (T-T or C-T)
27
What DNA repair enzyme repairs thymidine dimers?
DNA photolyase
28
Base excision repair is used for what types of damage?
single-base mismatches, non distorting alterations (eg depurination)
29
What enzymes perform base excision repair?
DNA glycolases, AP lyase (part of DNA polymerase B), DNA ligase
30
Nucleotide excision repair is used for what types of damage?
Chemical adducts that distort DNA (pyrimidine dimers, BPDE-guanine adducts, cisplatin adducts)
31
If nucleotide excision repair isn't working what disorder do you get?
Xeroderma pigmentosum
32
What type of damage is mismatch excision repair used for?
Mismatched base in daughter strand
33
What enzymes perform mismatch excision repair?
helicase/endonuclease, DNA polymerase d, DNA ligase
34
If mismatch excision repair doesn't function properly what disorder do you get?
Hereditary nonpolyposis colorectal cancers
35
What are the two types of recombination repair?
nonhomologus end joining (NHEJ) and homologous recombination
36
Double-strand breaks and interstrand cross linking requires what type of repair mechanism?
Recombination repair- NHEJ or homologous recombination
37
How does nonhomologous end joining work? What enzyme does this?
Damaged ends filled in and joined; some base pairs may be missing.
DNA ligase
38
How does homologous recombination work? What enzymes perform this repair? What is the associated disorder?
Damaged duplex is repaired using information on undamaged homologous duplex.
Exonucleases, DNA polymerase, MER system
BRCA1/2 breast cancer
39
What kind of repair mechanism is used for stalled RNA polymerase during transcription (NOT replication)? What disorder is associated with it?
Transcription-coupled repair (TCR)
| Cockayne syndrome
40
What repair mechanism is used for unprepared thymine dimers or apurini AP sites? What enzymes perform this repair mechanism?
```
Translesion synthesis (bypass synthesis)
DNA polymerase
```
41
What is DNA glycosylases role in base excision repair?
enzyme-mediated "flipping out" of base from the helix
enzyme probes for damage
if it finds an incorrect base- cleaves glycosyl bond connecting base with sugar
42
What enzyme has DNA glycosylase function?
DNA polymerase
43
How do nucleotide and base excision repairs differ?
Base excision repair removes a single base
Nucleotide excision repair removes a lesion-containing strand (multiple bases) and leaves a large gap for DNA polymerase and ligase to repair
NER scans DNA for distortion in double helix instead of a specific base change. Good for repairing thymine dimers.
44
When is transcription-coupled repair used?
cells link RNA polymerase with DNA repair to preferentially direct DNA repair to sequences that are being actively transcribed
45
How does transcription-coupled repair work?
RNA polymerase stalls at lesions and directs repair machinery there
works with BER, NER and others
It's specific for the strand being transcribed- non transcribed strand repaired at the same rate as DNA not being transcribed
46
What occurs if there is a defect in transcription-coupled repair? Why?
Cockayne's Syndrome- growth retardation, skeletal abnormalities, sensitivity to sunlight
RNA polymerase is permanently stalled at sites of damage in important genes
47
What are causes of double strand breaks?
Ionizing radiation, replication errors, oxidizing agents and other metabolites
48
Why is non-homologous end joining generally ok for double-strand break repairs?
Very little of our genome is used for protein-coding
49
What enzyme removes errors missed by proofreading by detecting distortion caused by mispairing? What is this repair mechanism called?
DNA polymerase
| Mismatch repair
50
If there is a mutation in mismatch repair gene what occurs? Why?
HNPCC- colon cancer
| cells accumulate mutations at high rate
51
What are the major differences between RNA and DNA?
RNA is single-stranded, has ribonucleotides, uracil, more unstable than DNA, can fold into complex 3D structures allowing some RNAs to have precise structural and catalytic functions
52
What are the three main types of RNA? What are their functions?
rRNA- a structural and functional component of ribosomes
tRNA- carry AAs to ribosomes
mRNA- direct carrier of genetic information
53
What are the functions of snRNA, siRNA, miRNA?
small nuclear RNA- direct the splicing of pre-mRNA to form mRNA
small interfering RNA- regulate eukaryotic gene expression by degrading select mRNA
micro RNA- regulate gene expression by blocking translation of selective mRNA
54
What are the functions of RNA Pol I, II, III?
I makes rRNA
II makes mRNA
III makes tRNA
55
What is the directionality of RNA polymerase? Does it need a primer?
5' to 3'
| no primer
56
What is the name of the non-template strand that will be identical to the sequence of RNA that will be produced?
coding (sense) strand
57
What is the site where the basal transcription factors and the RNA polymerase will bind called? Where is usually positioned compared to the gene?
Transcription start site
| +1 position of the gene- some genes have multiple start sites
58
The poly A tail represents the
transcription stop site
59
What is the linear sequence of DNA from start to stop site called?
transcription unit
60
What do initiation factors bind to? Where is related to the gene? What do they recruit?
Promoter
Upstream of the start site
Recruit RNA polymerase
61
What are enhancers/silencers?
Short sequences present upstream, downstream, or in transcription unit, sites for binding additional transcriptions factors, influence rate of transcription
62
What is the order of transcription factors binding to DNA?
TBP of TFIID binds to TATA box (causes distortion in DNA)
TFIIB
TFIIF
RNA Pol II
TFIIE
TFIIH (helicase activity)
all of these join to form transcription initiation complex
63
What are the functions of transcription factors?
- help position the RNA polymerase
- aid in pulling apart the two strands of DNA
- release RNA polymerase from the promoter into the elongation mode once transcription has been initiated
64
If assembly of the transcription initiation complex and initiation fails to work properly what three disorders can you get?
xeroderma pigmentosum
Cockayne syndrome
Trichothiodystrophy
65
What modification is placed on the 5' end of mRNA? Why?
Capping enzyme adds a 7-methyl guanosine cap with a 5-5' diphosphate linkage
protects against degradation and helps to bind mRNA to ribosome for translation
66
What are two types of chromatin remodeling and what are their enzymes?
```
Histone acetyl transferase (HAT)- adds acetyl group to histones, reduces positive charge and loosens interaction with DNA
Histone deacetylase (HDACs)- adds back the acetyl group and reverses the action of HAT
```
67
If histone deacetylase just worked on some DNA what will happen to DNA replication/transcription?
replication/transcription will decrease due to HDAC reverse HAT's loosening work
68
What destabilizes the interaction of RNA with RNA polymerase at the end of transcription?
the RNA transcript forms a self complementary hairpin followed by a poly U tail which destabilizes the interaction
69
What is the removal of introns or non-coding sequences called? What directs it?
splicing
| snRNA
70
What causes fragile X mental retardation (FMR1)?
aberrant methylation
FMR1 gene encodes for protein with neurological function
DNA sequence has >200 CGG repeat (normal has 30)
expansion makes it susceptible to methylation of cytosine which silences the gene even though the triplet expansion is upstream of the proteins doing sequence because methylation repeat region extends into the promoter region.
71
In what phase does chromosome duplication take place?
S phase (DNA synthesis phase)
72
What happens during M phase?
Chromosome segregation and cell division
73
What is the long phase following M phase called and what can it be further divided into?
Interphase: Gap 1 phase, S phase, G 2 phase
74
What does G0 phase mean?
Nutrient or environmental conditions are not appropriate for division, cells arrest during G1 phase
75
What happens during G1 phase?
RNA and protein synthesis
Cell growth
NO cell division
76
What happens during S phase?
DNA replication
Histone synthesis
Centrosomes formed
Chromosome duplication
77
What happens during G2 phase?
Preparation for mitosis
78
Where is the restriction point and what is its function?
At the end of G1 phase before the G1 checkpoint
| Growth factors stall the cell here
79
What does the G1 checkpoint check for? Where do you find it?
corrects any DNA damage (chemical modifications) before continuing
end of G1 phase
80
If there is DNA damage what checkpoint will find it? What will result from this DNA damage?
G1 checkpoint
| activates kinase that will phosphorylate (activate) p53
81
What does G2 checkpoint check for? Where do you find it?
Verify completeness of genomic duplication
| End of G2 phase
82
What does the metaphase checkpoint check for?
Ensures chromosomes are attached to mitotic spindle
83
Describe activation of the cell cycle
Myc activated and generates G1 cyclin in the presence of growth factors -> G1-CDK inhibits Rb (phosphorylation) -> Rb releases E2F -> E2F produces Cyclin E and Cyclin A (keep Rb inactive/E2F active)
84
What do Cdks require to be partially active? Fully active?
Cyclins make them partially active
| Phosphorylation by CAKs fully activate them
85
What inactivates the cyclin-Cdk complex by phosphorylation and what dephosphorylates it? By binding it?
WEE1 kinase phosphorylates and CDC25 phosphatase dephosphorylates
p27 is a CKI
86
How does a cyclin partially activate a Cdk? How does CAK fully activate a Cdk?
without cyclin bound the active site of Cdk is blocked by T loop
binding of cyclin causes T-loop to move out of active site
phosphorylation of Cdk at T-loop fully activates enzyme
87
What type of inheritance is post axial polydactyly?
autosomal dominant inheritance
88
What type of inheritance causes a trait to be expected in every generation? What is this transmission called?
autosomal dominant inheritance
| vertical transmission
89
What type of inheritance is tyrosinase-negative albinism?
autosomal recessive inheritance
90
First cousins mate and their kid has a problem. What type of inheritance did the problem probably have?
autosomal recessive
91
Duchenne muscular dystrophy is an example of what type of gene inheritance?
x-linked recessive
92
Hypophosphatemia is an example of what type of gene inheritance?
x-linked dominant
93
How are sons and daughters affected by a mother with an x-linked dominant disorder?
100% daughters will have it
| 50% of sons will have it
94
What is the penetrance of a disorder that shows phenotype in 9 out of 100 people that have the genotype?
9% penetrance
95
Retinoblastoma is an example of what type of inheritance? What is the penetrance of it?
autosomal dominant
| 90%
96
Neurofibromatosis is a disorder that portrays
variable expressivity
97
Osteogenesis imperfecta is an example of what
locus heterogeneity
98
what is locus heterogeneity
mutations on different chromosomes can exhibit the same phenotype individually
99
What are the structural features of the mature oocyte and what are the surrounding layers of accessory cells?
```
proximal to distal
nucleus
plasma membrane
perivitelline space
zona pellucida
corona radiata
```
100
What are the structural features of the mature sperm?
Head: acrosome and nucleus
Neck
Tail: middle piece (mitochondria), principle piece, end piece
101
where does fertilization occur?
ampulla (distal 2/3 of fallopian tube)
102
What are the four general steps of fertilization?
Step 1: capacitation and passage of sperm through CR
Step 2: penetration of ZP
Step 3: fusion of PM of oocyte and sperm
Step 4: completion of second meiotic division and fusion of male and female pronuclei
103
What is capacitation
glycoprotein coat and seminal plasma proteins removed from plasma membrane of sperm
104
What is the acrosome reaction
acrosome releases enzymes (hyaluronidase) so sperm can pass through corona radiata
105
What enzymes help the sperm penetrate the ZP? Where on the sperm do the enzymes come from?
esterases, acrosin, neuraminidase
| from acrosome
106
What is the result of the zone reaction?
block polyspermy
107
When the head and tail of the sperm enters the oocyte cytoplasm, what doesn't enter the oocyte?
mitochondria
108
Fusion of the male and female pronuclei makes the
zygote
109
When does cleavage begin? By what day is there a morula?
Cleavage starts at 30 hours
| Morula at 3 days
110
What happens during cleavage?
increase in cell number; each cell is smaller
overall embryo size is unchanged
morula develops
111
Identify the parts of the blastocyst
ICM
trophoblast (gives rise to the placenta)
blastocyst cavity
112
Describe the early derivatives of the trophoblast and their functions
cytotrophoblast: stem cell layer, mitotically active
synctiotrophoblast: proteolytic enzymes, hCG, responsible for implantation and initiation of pregnancy
early pregnancy factor (immunosuppressant)
113
What are derivatives of the ICM
epiblast and hypoblast
114
Define the epiblast, amnion, and amniotic cavity
all come from ICM
| ectoderm, amnion, amniotic cavity derived from epiblast
115
What are the derivatives of the hypoblast
prechordal plate
primary and secondary yolk sac (umbilical vesicle)
extra embryonic mesoderm
116
Explain the development of the primitive and secondary yolk sac
the only difference is time
| primary yolk sac remains can be seen as cystic features in the placenta
117
Where does the extra embryonic mesoderm come from? What are the two types? What do they line?
comes from hypoblast
somatic: coats the inside of the trophoblast layer and covers the amnion
splanchnic: lines the yolk sac (umbilical vesicle)
118
What are the derivatives of the extra embryonic mesoderm?
```
Connecting stalk (somatic)
Primitive blood (splanchnic)
Chorion (somatic)
```
119
Where does the connecting stalk form? What does it form from? What does it eventually become?
forms at embryonic pole
extra embryonic somatic mesoderm
umbilical chord
120
What does primitive blood develop from? Where can you find it?
extra embryonic splanchnic mesoderm
| forms in wall of yolk sac
121
What does chorion develop from? What does it eventually become?
extra embryonic somatic mesoderm
| becomes placenta
122
Describe assisted reproductive technologies
- place oocytes in Petri dish with capacitated sperms: in vitro fertilization of oocytes occur
- cleavage of zygotes in culture medium until 4 or 8 cell stages
- transfer 1-2 cleaving embryos into uterine cavity by way of catheter
123
What are signs and symptoms of abnormal implantations?
vaginal bleeding, pelvic pressure or pain, enlarged uterus, hyperemesis gravidarum (morning sickness)
124
What is formed during gastrulation? What week of pregnancy does this take place?
3 layers: ectoderm, mesoderm, endoderm
| week 3
125
What replaces the hypoblast?
endoderm
126
What does primitive streak form from? Where on the embryo will it form? What are the three things that will form from the primitive streak?
- forms in epiblast
- forms at caudal end of embryo
- forms primitive knot (primitive node), primitive groove, primitive pit
127
What's unique about teratomas
have all three different germ layers in them
128
Explain the formation of the notochord
Extends from primitive node (knot) anterior to the prechordal plate
129
What is the role of the notochord?
Template for vertebral column, induces neural plate (nervous system)
130
Identify the major classes of mesoderm
Paraxial, intermediate, lateral plate
131
What are the derivatives of the paraxial mesoderm?
somites: myotome, dermatome, axial sclerotome (vertebral skeleton)
132
What are the derivatives of the intermediate mesoderm?
urogenital: kidneys and gonads
133
What are the derivatives of the lateral plate mesoderm?
connective tissue: blood, lymph, mesenteries, cardiovascular
134
Summarize what happens during weeks 1-3
Week 1: formation of the inner cell mass
Week 2: formation of epiblast and hypoblast
Week 3: gastrulation (three layers)
135
How do transcription factors interact with DNA? What are their functions?
They are proteins with domains that bind to promoter or enhancer regions and domains that interact with RNA polymerase II
Regulates the amount of mRNA that the gene produces
136
What is the common subunit that is upstream of cAMP production when it comes to GPCRs?
Gsa
137
In GPCR pathway what generates cAMP?
Adenylyl cyclase
138
What does cAMP activate? How does the binding of cAMP affect the structure of this protein?
activates cAMP-dependent protein kinase (PKA)
| binding of 2 cAMP molecules to regulatory subunits of tetramer results in release of active C subunits
139
How can phosphorylation by PKA regulate proteins?
1) phosphate group can form a part of structure that other proteins recognize
2) activation or inactivation of enzymatic target proteins
3) alteration of intracellular localization of target proteins
4) alterations in abundance of target proteins
140
How does the cholera toxin affect the G protein?
Keeps Ga in GTP active form indefinitely
leads to 100 fold increase in cAMP
PKA phosphorylates the CFTR Cl- channel
leads to secretion of water
141
Define desensitization
| When is it important
ability to turn off or reject the signal
| important in cancer cell cycle
142
What are five ways to attenuate a signal?
- hormone levels drop
- remove the signaling molecule: phosphodiesterase will remove cAMP/cGMP
- receptor sequestration (in early endosomes)
- receptor destruction (endosomes and lysosomes, proteases)
- GRKs
143
How do GRKs work?
G protein receptor kinases
phosphorylate the recent such that another protein called arrestin will bind to the 3rd intracellular loop and prevents Ga from interaction with the third loop
Ga-GDP does NOT convert to Ga-GTP
144
What is the function of Gi/oa G-protein?
inhibits AC
145
How does Gqa G-proteins differ from Gsa G-proteins?
activates PLC instead of AC
146
What does PLC stand for and what does it cleave? What does this produce?
phospholipase C claves membrane protein PIP2
| produces IP3 and DAG 2nd messengers
147
What does IP3 do? Is it diffusible or membrane bound? Where does it come from?
Comes from cleavage of PIP2 by PLC, diffusible
triggers release of Ca from ER by binding to IP3-gated Ca channel
Ca is a second messenger too!
148
Where does DAG come from? Is it diffusible or membrane bound? What does it do? What does it work with?
Comes from cleavage of PIP2 by PLC, membrane bound
| Works with Ca released by IP3 to bind to protein kinase C (PKC) causing a conformation change so that it is activated
149
Ligand binding to a receptor tyrosine kinase induces what?
Dimerization of two receptor monomers
| autophosphorylation occurs
150
Why are RTKs important?
mediate growth factor signals
151
What is the function of autophosphorylation of RTKs?
causes the receptor to act as a scaffold to recruit other proteins to the plasma membrane
152
The SH2 domain of what protein binds to what on the RTKs?
SH2 domain of Grb2 binds to phosphotyrosine on receptor tyrosine kinase
153
The SH3 domain of what protein binds to what
SH3 domain of Grb2 binds to pralines in SOS
154
What does SOS bind to after it is bound by SH3 domain?
binds to Ras
155
Ras is known for being the first what
first discovered human oncogene
| plays crucial role in cell division and a frequent mutation in cancer
156
What does Ras bind to after being bound by??
SOS binds Ras which then binds Raf
157
Raf binds? Which binds to?
Raf binds Mek which binds Map kinase (Erk)
158
What are the functions of Erk?
changes in protein activity
| changes in gene expression
159
IRS-1 acts as a what in what signaling pathway?
acts as a scaffolding protein: binds GRB-2 or PI3K
| RAS-dependent and RAS-indepdnet signaling via RTK
160
Describe the process of JAK-STAT receptor signaling pathway
Receptors bind cytokines, dimerize, and bind JAKs
JAKs phosphorylate each other and the receptor
Receptor binds and phosphorylates STATs
STATs dissociate from receptor, dimerize, and translocate to nucleus
161
Describe the process of Smad receptor signaling pathway
| What does it control
type 2 binds TGF-B which dimerizes with a type I
activated type I phosphorylates R-Smad which will complex with a Co(common)-Smad and migrates to nucleus
Smads can control cell proliferation
162
Adherens junctions bind to what cytoskeletal filament?
| What cell adhesion molecule facilitates the binding on the extracellular domain??
actin
| classical cadherins
163
Classical cadherins undergo what type of interactions?
homophilic
164
Desmosomes bind to what cytoskeletal filament? What cell adhesion molecule do they use?
Intermediate filaments
| non-classical cadherins
165
Non-classical cadherins in a desmosome undergo what type of interactions?
homophilic
166
Non-classical cadherins in a hemidesmosome undergo what type of interactions?
What do non-classical cadherins in hemidesmosomes bind to on the extracellular domain?
heterophilic
| integrin
167
What intracellular cytoskeletal protein do hemidesmosomes bind to?
intermediate filaments
168
Why do cell to cell adhesions require a shit ton of cadherin bindings?
Because cadherins have hella low affinity for each other
169
Why are N and E cadherins important in development?
They force cells to "sort out" according to whatever cadherin they have
170
Adherens junctions form what big picture structure among cells? What lies parallel to this structure and how is it tethered to the plasma membrane?
Adhesion belt
| Contractile bundle of actin filaments
171
What is a common cause of sudden cardiac death in young people? What type of adheren protein is it?
desmocollin
| non-classical cadherin
172
Pemphigus foliaceus is an autoantibody-mediated blistering disease in which antibodies are made against what? What does this cause?
desmoglein 1
| causes a loss of adhesion of keratinocytes in the superficial layers of the epidermis
173
What is the main functional protein involved in tight junctions?
claudins
174
What makes up tight junctions
focal connections
175
What are the three conserved polarity complexes controlling and maintaining the polarization process of cells?
Par, Crumbs, Scribble
176
The establishment of cell-cell contacts and subsequent apiece-basal polarization requires what?
E-cadherin-mediated cell-cell adhesion
177
Gap junctions are formed by what individual protein? What do you call it when a bunch of these little proteins come together to make hemichannel?
connexins
| connexons
178
What is the largest size molecule that can make it through a connexon?
1000 daltons
179
explain how gap junctions open and close
increase in calcium ion concentration in the cytoplasm will cause a cell to close it's gap junction so that it cannot spread to neighboring cells
180
In most connective tissues the matrix macromolecules are secreted largely by cells called?
What is the predominant macromolecule in the extracellular matrix?
fibroblasts
| collagen
181
What separates epithelia from connective tissue?
| What produces this barrier?
basal lamina
| both cells on the either side of the basal lamina produce it
182
What are two major proteins in the basement membrane?
type IV collagen and laminin
183
The formation of focal adhesions is dependent on the activity of what enzyme?
Src/FAK complex
184
What is the predominant hemoglobin in adults? What subunits make up this hemoglobin?
What about the one that is less common?
```
Hb A (a2B2) 97%
Hb A2 (a2d2) 3%
```
185
What is fetal hemoglobin called and what subunits make it up?
Hb F (a2y2) 0.5%
186
What is the difference between sickle cell trait and sickle cell disease?
Trait is heterozygote
| Disease is homozygote
187
What causes sickle cell anemia?
Substitution of valine for glutamic acid at amino acid #6 in B globin
causes polymerization of hemoglobin
188
What is the current treatment for sickle cell anemia?
Hydroxyurea to induce expression of HbF and to address inflammation
189
How does the binding of oxygen to hemoglobin affect hemoglobins structure?
binding of O2 to Fe of a globin subunit pulls the proximal F8 histidine down which pulls on the global FG-helix and changes the interaction with the other global chains in Hb
190
How does 2,3-BPG affect oxygen affinity in hemoglobin?
signals Hb to let go of O2 by reducing Hb affinity of O2
191
What is the Bohr Effect?
active tissues produce acid which makes the pH drop
binding affinity of Hb for O2 decreases as pH decreases because histidine picks up H+ from tissue and changes Hb conformation
192
Why does fetal hemoglobin have a higher affinity for O2 than mom's hemoglobin?
fetus hemoglobin does not bind 2,3-BPG so it has a higher affinity
193
On average how much transferrin is bound to iron?
30%
194
What is the lab test that tells us how much transferrin we have? How will this lab value differ if we have iron deficiency or overload?
Total iron binding capacity (TIBC)
Iron deficient = high TIBC
Iron overload = low TIBC
195
1) Porphobilinogen Deaminase (PBG Deaminase) is associated with what porphyria?
2) What metabolites will be elevated if this enzyme is defective?
3) what are the symptoms of this porphyria?
4) In what tissue type is the enzyme defective?
1) acute intermittent porphyria
2) ALA and PBG
3) periodic attacks of abdominal pain and neurologic dysfunction
4) hepatic
196
1) uroporphyrinogen III synthase is associated with what porphyria?
2) What metabolites will be elevated if this enzyme is defective?
3) what are the symptoms of this porphyria?
4) in what tissue type is the enzyme defective?
1) congenital erythropoietic porphyria
2) uroporphyrinogen I and uroporphyrin I
3) photosensitivity, red color in urine and teeth; hemolytic anemia
4) Erythrocytes
197
1) uroporphyrinogen decarboxylase is associated with what porphyria?
2) What metabolites will be elevated if this enzyme is defective?
3) what are the symptoms of this porphyria?
4) In what tissue type is the enzyme defective?
1) porphyria cutanea tarda (PCT)
2) uroporphyrinogen III, which converts to uroporphyrinogen I and other oxidation products
3) red-wine colored urine, photosensitivity resulting in cesicles and bullae on skin of exposed area
4) hepatoerythropoietic
198
1) protoporphyrinogen IX oxidase is associated with what porphyria?
2) what are the symptoms of this porphyria?
3) In what tissue type is the enzyme defective?
1) variegate porphyria
2) photosensitivity and neurologic symptoms and development delay in children
3) hepatic
199
what is the most common porphyria in the US?
PCT
200
patient hemolytic anemia or internal hemorrhage could present with what type of jaundice?
pre-hepatic
201
what substance will be elevated in the blood in pre-hepatic jaundice conditions
unconjugated (indirect) bilirubin
202
what substances will be elevated in the urine in pre-hepatic jaundice?
none will be elevated
203
what substances will be elevated in the blood of a patient with intra-hepatic jaundice?
conjugated (direct) bilirubin if the issue is involved in secretion from liver
unconjugated (indirect) bilirubin in the issue is involved in absorption into the liver
AST/ALT
204
what substances will be elevated in the urine of a patient with intra-heptaic jaundice?
conjugated bilirubin
205
what substances will be elevated in the blood of a patient with post-hepatic jaundice?
ALP
| conjugated (direct) bilirubin
206
what substances will be elevated in the urine of a patient with post-hepatic jaundice?
conjugated/direct bilirubin
207
what substances will be absent from the urine of a patient with post-hepatic jaundice?
urobilinogen
208
what substances will be absent from the doodoo of a patient with post-hepatic jaundice?
stercobilin
209
breakdown of heme into bilirubin normally occurs where
macrophage of the Reticuloendothelial System
210
neonatal jaundice can be attributed to excess levels of what substance in their blood
neonatal jaundice is also referred to as what
unconjugated bilirubin
| physiological jaundice
211
list the causes/contributing factors to neonatal jaundice
breakdown of fetal hemoglobin as it is replaced with adult hemoglobin
immature hepatic metabolic pathways - unable to conjugate and excrete bilirubin
deficiency of UDP-GT enzyme
212
explain why phototherapy is a successful treatment in neonatal jaundice
converts bilirubin to a more soluble form
213
explain why IM injection of tin-mesoporphyrin is a successful treatment in neonatal jaundice
strong inhibitor of heme oxygenase
214
what is crigler-najjar syndrome type I
complete absence of UDP-GT leads to severe hyperbilirubinemia
bulirubin accumulates in baby brain
causes kernicturus
215
what is criggler-najjar syndrome type II
mutation in UDP-GT gene to yield 10% normal activity
216
what is gilbert syndrome
reduced activity of UDP-GT (25% activity)
| serum BR is less than 6mg/dL
217
what is hepatitis
inflammation of liver, leads to liver dysfunction
218
RNA polymerase utilizes what cofactor at the active site
Magnesium (Mg)
219
transcription starts at the +1 position. what nucleotide is usually present at the +1 position?
A or G
220
describe the cap that goes on the 5' end of mRNA
7-methyl guanosine
| 5'-5' diphosphate linkage
221
what is the enzyme responsible for easing superhelical tension in transcription
DNA gyrase
222
explain Fragile X Mental Retardation (FMR1)
lot of Cs and Gs.
Cs get methylated and if they methylation occurs in the promoter, the gene will be silence, leading to the mental insufficiency
223
explain how streptomycin works as an antibiotic
affects the 30s small subunit of the bacterial ribosome, blocking initiation
224
explain how tetracyclines work as antibiotic
affect the 50s large ribosomal subunit of bacteria, disrupting elongation
225
how do clindamycin/erythromycin kill bacteria
block the 50s large ribosomal subunit of bacteria, disruption translocation of the ribosome
226
what is a polysome
10-100 ribosomes on one mRNA. similar to a gangbang. mad efficient
227
what are the stop codons?
UGA
UAA
UAG
228
amino acids bind to which end of the tRNA
3' CCA terminal region
229
what enzyme is responsible for synthesizing peptide bonds?
peptidyl transferase
230
what is the mitochondrial sorting signal?
N terminal hydrophobic α-helix
231
what is the cytoplasmic sorting signal?
there is no cytoplasmic sorting signal. it is the default path
232
proteins wanting to enter the nucleus can pass through nuclear pores. but only if they have a certain amino acid sequence. what is the nuclear
localization signal
Four continuous basic residues (Lys and Arg)
233
peroxisome sorting signal is what
C-terminal SKL sequence
234
what is the signal that allows proteins to be secreted from the ER and enter the lysosome?
Mannose-6-phosphate
235
what is the signal for proteins destined to end up in the ER lumen?
C-terminal KDEL
236
proteins destined for extracellular secretion must have what sorting signal(s)
lack of ER retention signal
| tryptophan rich signal region
237
proteins destined for plasma membrane must have what sorting signal(s)
N terminal apolar region (stop transfer sequence)
238
what is the ER-targeting signal peptide?
1 or 2 basic amino acids (Lys or Arg) near N terminus
| An extremely hydrophobic sequence (10-15 residues) on C terminus of the basic residues
239
explain the process of how a protein enters the ER lumen
A signal recognition particle (SRP) binds to the ER-targeting signal and the ribosome during translation.
SRP wraps itself around ribosome-mRNA-peptide complex, tethering it to
ER membrane and halting translation temporarily
Translation resumes when protein directed into the ER lumen. Enzymes on luminal side cleave the signal to release the protein
240
In glycosylation, what residues are involved in O-glycosidic linkages?
Hydroxyl groups of Ser or Thr residues.
241
In glycosylation, what residues are involved in N-glycosidic linkages?
Asparagine
