molecular/cellular Flashcards
(79 cards)
1
Q
histones are rich in amino acids?
A
lysine and arginine
2
Q
heterochromatin vs euchromatin
A
heterochromatin is condensed, transcriptionally active, sterically inaccessible
euchromatin is less condensed, transcriptionally active, sterically accessible
3
Q
DNA methylation
A
cytosine and adenine are methylated on the template strand so that mismatch repair enzymes can distinguid between new and old strands
4
Q
histone methylation vs acetylation
A
methylation inactivates transcription of DNA
acetylation relaxes DNA coiling, allowing transcription
5
Q
name two purines
A
adenine and guanine
6
Q
name to pyrimidines
A
cytosine
uracil
thymine
7
Q
which amino acids are needed for purine synthesis?
A
glycine
aspartate
glutamine
8
Q
what is a nucleoside
A
base + ribose
9
Q
what is a nucleotide
A
base + ribose + phosphate
10
Q
how to make a purine
A
start with a sugar + phosphate (PRPP) then add a base
11
Q
how to make a pyrimindine
A
make a temporary base (orotic acid)
then add a sugar and a phospahte
then modify the base
voila a pyrimidine
12
Q
what enzyme converts ribonucleotides to deoxribonucleotides
what inhbits this enzyme?
A
ribonucleatide reductase
hydroxyurea is an inhibitor
13
Q
inhibitors of dihydrofolate reductase
A
methotrexate -humans
trimethoprim (TMP) -bacteria
pyrimethamine - protozoa
14
Q
5-FU
A
inhibits thymidylate synthase
15
Q
mycophenolate and ribavirin inhibit IMP dehydrogenase
A
IMP –> GMP
- decrease GMP
16
Q
adenoside deaminase deficience
A
-excess ATP and dATP imbalencse nucelotide pool via feedback of ribonucleotide reuctase –> prevents DNA synthesis and thus decreases lymphocyte count
This is one of the major causes of SCID - autosomal recessive
17
Q
Lesch-Nyhan syndrom
A
Defectiv purine salvage due to absent HGPRT
- converts hypoxanthine to IMP
- converts guanine to GMP
- no HGPRT, build up guanine and hypoxanthine which leads to increased xanthine –> uric acid
the symptoms: H hyperuricemia G gout P pissed off (aggression, mutilation) R retardation T dysTonia
treat: allopurinol and febuxostat (2nd line)
18
Q
Febuxostat
A
xanthine oxidase inhibitor
-second line in the treathment of lesch hyhan syndrome
19
Q
name the two amino acids that have only 1 codon code
A
methione AUG
tryptophan UGG
20
Q
origin of replication
prokaryotes vs eukaryotes
A
prokaryotes 1 origin as it is circular
eukarytoes multiple
21
Q
helicase
A
unwinds DNA template at replication fork
22
Q
ssbp single stranded BINDING proteins
A
prevent strands from reannealing
23
Q
DNA toperoisomerse (DNA gyrase in prokaryotes)
A
creartes single or double stranded break in the helix to add or remove supercoils
24
Q
primase
A
makes and RNA primer on which DNA Pol III can initiate replication
25
DNA pol III
- prokaryote only
- 5'-->3' synthesis
- proofreads with a 3'-5' exonuclease
26
DNA pol 1
prokaryote only, degrades the RNA primer and replaces it with DNA
27
telomerase
an RNA dependant DNA polymerase that adds DNA to 3' ends of chromosomes to avoid loss of genetic material with every duplication
28
negative inducible operons
- a repressor protein is normally bound to the operator
- but if an inducer is pressent it binds to repressor, changing its shape and is now able to bind to operator.
example: lac operon, where the incuder is allolactose
29
negative repressible operons
- transcription normally takes place
- repressor proteins are produced by a regulator gene but are unable to bind to the operator in their normal conformation.
- corepressor bind to the repressor protein - conformation is active
- the activated repressor can bind to the operator and prevent transcription
- example is try operon where tryptophan is the corepressor
30
nucleotide excision repair
| -damaged in which disease?
-xeroderma pigmentosum (prevents repair of pyrimidine dimers )
- specific endonucleases relase the oligonucleotide-containing damged base pairs
- DNA polymerase and ligase fill and reseal the gap
- repairs bulky helix distorting lesions like dimers!
31
Base excision repair
| -what is it important for>
repair of spontaneous/toxic deamination
- base specific gycosylase recognizes the altered base and creats a apurinic/apyrimidinic) site.
- one or more nucleotides are removed by AP endonuclease which cleaves the 5'end
- Lysase cleaves the 3' end
- DNA polymerase-B fills the gap
- DNA ligase seals
32
Mismatch repair
| what disease is this defective?
Hereditary nonpolyposis colon cancer (lynch syndrome)
-newly synthesized strand is recognized, mismatch nucleotides are removed, and the gap is filled and resealed.
33
nonhomolousous end joining
| mutated in?
ataxia telangiectasia
- brings together 2 end of DNA fragments to repair double-stranded breaks. No requirement for homology.
- double strand DNA repairr
34
mRNA stop codons
UAA u are away
UAG u are gone
UGA u go away
35
proteins that can bind DNA
- -transcription factors
- steroids
- thyroid proteins
- vitamin D receptors
- retinoic acid receptors
- DNA transcription repressor proteins
36
prokaryote RNA Pol
-multisubunit complex it makes all 3 kinds of RNA
37
RNA pol 1 makes
-rRNA
18s, 5.8s, 38s
-form essential ribosomal compoenents
-synthesized in the nucleolus of the nucleus
38
RNA pol II makes
- mRNA
- small nuclear RNA - involved in mRNA splicing and transcription regulation
- micro RNA - cause gene silencing via translation arrest on mRNA degradation
aside: adamantin, found in amanita phalloides (death cap mushroom), inhibits RNA pol II -- causes severe hepatoxity if ingested
39
RNA pol III makes
tRNA
| and the 5s rRNA (componenet of the 60s)
40
what happens to to make mature mRNA in the nucleus?
- cap the 5' end (addition of the 7-methylguanosine cap)
- polyedenylation of 3' end (~ 200 A's) that a lot of A's eh
- splicing out of introns
capped, tailed and spliced is mRNA
41
what is the poly A signal?
AAUAAA
42
splicing
1. primary transcript combines with small nuclear ribonocleoproteins (snRNPs) and other proteins to form the spliceosome
2. lariat shaped intermediate is formed
3. lariate is release to precisely remove introm and join 2 exons
anti-smith antibodies in SLE are antibodies to snRPS!
anti-U1 RNP antibodies are assoc. mixed connective tissue disease
43
give an example of an abnormal splicing related to a disease
b-thalassemia
44
tRNA
3' end contains the CCA (can carry amino acids)
-aminoacyl-tRNA synthetase uses ATP and adds the amino acid to the 3'end
-T arm contains a sequence necesary for tRNA-ribosome binding
D-arm contains dihyrouracil residues needed for tRNA recognition by the correct aminoacyltRNA synthetase
45
Protein synthesis:
| initiation
-initiated by GTP hydrolysis; initiation factors (eukaryotic IFs) help assemble the 40s ribosomal subunit with the initiator tRNA and are released when the mRNA and the ribosomal 60S subunit assemble with the complex
eukaryotes 40S +60S --> 80s
Prokaryotes 30S + 50S --> 70S
46
Protein synthesis: elongation
1. amino acyl-tRNA binds to A site (except for initiator methionine)
2. rRNA (ribozyme) catalyzes peptide bond formation, transfers growing polypeptide to amino aicd in A site
3. ribosome advance 3 nucleotides toward the 3'end of mrNA moving peptdyl TRNA to P site(translocation)
47
Protein syntheisis: termination
stop codon is recognizd by release factor and completed polypeptide is release from ribosome
48
tumor supressors in cell cycle
p53 and hyprophophorylated Rb normally inhibit the G1- S progression
mutations - li fraumeni syndrome
49
examples of permanent cell types
-remainin G0 regenerate from stem cells:
| neurons, skeletal and cardiac muscle and RBC
50
examples of stable (quiescent)
-enter G1 from G0 when stimulated - hepatocytes and lymphocytes
51
examples of labile cell types
never go to G0 divide rapidly from G1
they are most affected by chemo
-bone marrow, gut epithelium, skin, hair follicles, germ cells
52
Rough endoplasmic reticulum
-site of synthesis of secretory (exported proteins) and of N-linked oligosaccharide addition to many proteins (gycosylation)
in neurons, the nissel bodies which asre RER synthesize the peptide neurotransmitters for secretion
Free ribosomes synthesize cytosolic and organellar proteins
53
Smooth endoplasmic reticulum
- site of steroid synthesis and detoxification of drugs and poisons. Lacks surface ribosomes
note) liver hepatocytes and steroid producing cells of the adrenal cortex (aldosterone, cortisol, sex androgens GFR) are rich in SER
54
the golgi adds mannose-6-phosphate to proteins for trafficking to where?
lysosomes
a defect in this process causes I cell disease
55
Golgi
distribution center for proteins and lipids from the ER
endosomes are sorting centers for material from outside the cell or from the golgi, sending it to lysosomes for destruction or bacj to membrane/golgi for further use
56
what are some modifications done at golgi
mannose-6-phosphate to proteins for trafficking to lysosomes
- n-oligosaccharides on asparagine
- adds o-oligosaccharides on serine and threonine
57
I cell disease
- inhereted lysosomal storage disorder
- defect in phosphotransferase --> failure of the golgi to phosphorylate mannose residues on glycoproteins, thus proteins are excreted extracellularily instead of sent to lysosomes.
clinical
coarse faciaul features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes.
often fat in childhood
58
signal recognition particle SRP
-cytosolic ribonucleoprotein that traffics protein from the ribosome to the RER. Absent or dysfunctional SRP--> proteins accumulate in the cytosol.
59
COP I vesicular trafficing protein
send golgi through golgi (retrograde - further into cell) towards the ER
60
COP II
ER sends to golgi, golgi through golgi (anterograde towards vesicles to go to membrane)
61
Clathrin:
1. it helps moves things across the golgi trans (horizontal)
2. it helps bring in things from plasma menbrane then to endosome - receptor mediated endocytosis
and example is the LDL receptor
62
What membrane enclosed organelle is involved in catabolism of very long chain fatty acids, branched-chain fatty acids and amino acids?
peroxisome
63
microtubule
- cylindrical structure composed of a helical array of polymerraized heterodimers of alpha and beta tubulin
- each dimer had 2GTP bound
- incorporated into flagella cilia and mitotic spindles
- grows slow collapses quickly
64
molecular motor proteins
dynein = retrograde to microtubule
| kinesis - anterograde to microtubule
65
name some drugs that act on microtubules
think the acronym
microtubles get constructed very poorly
```
mebendazole (anti-helminthic)
griseofulvin (antifungal)
colchicine(anti gout)
vincristine/vinblastine (anti-cancer)
paclitaxel (anti-cancer)
```
66
cilia
9 + 2 arrangment of microtubules
67
Kartegener syndrome
| primary ciliary dyskinesia
- immotile cilia due to a dynein arm effect
- results in male and female infertility due to immotile sperm and dysfunctional fallopian tube cilia, respectively
- increase risk of ectopic pregnancy.
- can cause bronchiectasis, recurrent sinusitis, and situs inversus
68
Type 1 collagen
- most common 90%
| - bone (made by osteoblasts), skin, tendon, dentin, fascia, cornea, late would repair
69
type II collagen
- CARTILAGE (including hyaline)
- virtreous body, nucleus pulpous
cartwoolage
70
type III collagen
reticulin - skin
- BLOOD VESSELS
- uterus
- fetal tissue
- granulation tissue
type III deficient the vascular toe of Ehlers-Danlos
71
Type IV collagen
BASEMENT MEMBRANE!!!, basal lamina, lens
-defective in Alport syndrome, targeted by autoantibodies in goodpastures syndrome
72
Collagen synthesis in fibroblasts at the site of the RER
1. translation of collagen alpha chains - Gly-X-Y where X and Y are nomally proline or lysine, note collagen is 1/3 glycine
2. Hydroxylation of specific proline and lysine residues - this requires vitamin C
3. Glycosylation of pro-alpha chain hydroxylysine residues and formation and disulfide bonds --> tripple helix of 3 collagen alpha chains. problems forming this triple helix leads to osteogenesis imperfecta
4. exocytosis of procollagen into the extracellular space
73
Collegen synthesies outside of fibroblasts in the extracellular space
5. Cleavage of disulfide-rich terminal regions of pro collagen, transforming it into insoluble tropocollagen.
6. reinforcment of many staggered tropcollagen molecules by covalent lysine-hydroxylyside cross-linkage (cu-containing lysyl oxidase) to make collagen fibrils.
Problems with crosslinking leads to ehlers-danlos
74
Osteogenesis imperfecta
- brittle bone disease
- caused by a variety of gene defects
- autosomal dominant
- decreased production of otherwise normal type 1 collagen (type 1 is bone)
- problems forming the triple helix (this is step 3 in the fibroblast)
manifestations:
- multiple fractures with minimal trauma
- blue sclerae, due to the transulcency of the connective tissue over the choroidal veins
- hearing loss due to abnormal ossibles
- dental imperfections due to lack of dentin
75
Ehlers-Danlos
- faulty collagen synthesis
- hperetensible skin, tendancy to bleed -> bruise, hypermobile joints
- 6 + types
- inheretance and severity vary
- Autosomal dominant and recessive
- assoc joint dislocation, berry and aortic aneurysms and organ rupture
hypermobilityy type (joint instability) is the major type
classical type: joint and skin symptoms cause by a mutation in type V collagen
vascular type (vascular adn organ rupture) is a deficieny in type III collagen
76
Menkes disease
- imparied copper absorption and transport.
- recall copper is in lysyl oxidase which is needed for collagen fibrils
- results in brittle, kinked hair, growth retardation and hypotonia
connective tissue disease
77
Elastin
rich in proline and glycine and nonhydroylated forms.
- tropelastin with fibrillin scaffoliding
- cross linking takes place extracellularly and givs elastin its elastic properties.
- broken down by elastase (inhibited by a1-antityrpsin)
78
wrinkles of aging
decreased collagen and elastin production
79
marfan syndrome
caused by defect in fibrllin a glycoprotein that forms a sheath around elastin
