B&B Cell Bio Flashcards
(307 cards)
1
Q
Which cell cycle checkpoint is blocked by p53?<div><br></br></div><div>{{c1::G1 to S}}</div>
A
“<div><i>Hence a mutation can cause uncontrolled cell division</i><br></br></div><div><i>Also blocked by hypophosphorylated Rb <br></br></i><div><img></img></div></div>”
2
Q
Which cell cycle checkpoint is blocked by hypophosphorylated Rb?<div><br></br></div><div>{{c1::G1 to S}}</div>
A
“<div><i>Hence a mutation can cause uncontrolled cell division</i><br></br></div><div><img></img></div>”
3
Q
<div><b>Rhabdomyoblasts</b> are characterized by positive IHC staining for <b>{{c1::desmin}}</b> and <b>{{c1::myogenin}}</b> </div>
A
“<i>desmin is an intermediate filament of muscles cells; </i><i>malignant rhabdomyoblasts cause embryonal </i><b><i>rhabdomyosarcoma</i></b><div><b><i><br></br></i></b></div><div><i>myogenin<b> </b>is a transcription factor present in immature muscle cells</i></div>”
4
Q
<div>What process is used by <b>mismatch repair enzymes</b> to distinguish between <u>old</u> and <u>new</u> <b>DNA strands</b> in prokaryotes?</div>
<div><br></br></div>
<div>{{c1::DNA methylation}}</div>
A
template strand <b>cytosine</b> and <b>adenine</b> are methylated for this very purpose
5
Q
<div>What process takes <b>DNA</b> and makes more <b>DNA</b>? </div>
<div><br></br></div>
<div>{{c1::Replication}}</div>
A
“<img></img>”
6
Q
<div><div>What process takes <b>DNA</b> and makes <b>RNA</b>? </div><div><br></br></div><div>{{c1::transcription}}</div></div>
A
“<img></img>”
7
Q
<div><div>What process takes <b>RNA</b> and makes <b>protein</b>? </div><div><br></br></div><div>{{c1::translation}}</div></div>
A
“<img></img>”
8
Q
<div><div><div>DNA & RNA are made of <b>{{c1::nucleotide monophosphates}}</b> connected via a(n) {{c2::<b>phosphodiester</b>}} bond</div></div></div>
A
“<img></img>”
9
Q
<div>One feature of the <b>genetic code</b> is that it is {{c1::degenerate/redundant}}: most amino acids are coded by <i>multiple</i> codons </div>
A
<i><u>exceptions</u>: methionine and tryptophan are encoded by only 1 codon (AUG and UGG, respectively)</i>
10
Q
<div>One feature of the <b>genetic code</b> is that it is {{c1::commaless, nonoverlapping}}: it is read from a fixed starting point as a continuous sequence of bases</div>
A
<i><u>exceptions</u>: some viruses</i>
11
Q
<div>One feature of the <b>genetic code</b> is that it is {{c1::universal}}: genetic code is conserved throughout evolution</div>
A
<i>exceptions: mitochondria (in humans)</i>
12
Q
<div>What does <b>AUG</b> encode for in <i>eukaryotes</i>?</div>
<div><br></br></div>
<div>{{c1::Methionine (start codon)}}</div>
A
<i>rarely GUG is a start codon as well</i>
13
Q
<div><div>What does <b>AUG</b> encode for in <i>prokaryotes</i>?</div><div><br></br></div><div>{{c1::N-formylmethionine, or fMet (start codon)}}</div></div>
A
<i>fMet also stimulates neutrophil chemotaxis</i>
14
Q
<div>Which <u>three</u> sequences of bases are mRNA <b>stop codons</b>? </div>
<div><br></br></div>
<div>{{c1::<b>UGA</b>, <b>UAA</b>, <b>UAG</b>}}</div>
A
“<i>”“<b>U G</b>o <b>A</b>way, <b>U</b> <b>A</b>re <b>A</b>way, <b>U</b> <b>A</b>re <b>G</b>one””</i> “
15
Q
<div>The {{c1::origin of replication}} is a particular consensus sequence of base pairs in a genome where <b>DNA replication begins</b> </div>
A
“<div><i>may be <u>single</u> (prokaryotes) or <u>multiple</u> (eukaryotes)</i> </div><div><img></img></div>”
16
Q
<div>{{c1::AT}}-rich sequences are found in <b>promoters</b> and <b>origins</b> <b>of replication</b></div>
A
AT has 2 bonds vs 3 in GC-easier to break apart
17
Q
<div>The {{c1::replication fork}} is a Y-shaped region along the DNA template where <b>leading</b> and <b>lagging strands are synthesized</b> </div>
A
“<img></img>”
18
Q
<div>Which enzyme is responsible for <b>unwinding the DNA template</b> at the replication fork? </div>
<div><br></br></div>
<div>{{c1::Helicase}} </div>
A
“<img></img>”
19
Q
<div>{{c1::Single-stranded binding}} proteins <u>prevent</u><b> DNA strands from reannealing</b> during replication </div>
A
“<img></img>”
20
Q
<div>Which enzyme is responsible for <b>relaxing the DNA strand</b> by creating single- or double-stranded breaks in the DNA helix to add/remove supercoils? </div>
<div><br></br></div>
<div>{{c1::Topoisomerase}} </div>
A
“<div><img></img></div>”
21
Q
<div>Which enzyme is responsible for <b>making an RNA primer</b> on which DNA polymerase III can initiate replication (<u>prokaryotes</u>)? </div>
<div><br></br></div>
<div>{{c1::Primase}}</div>
A
“<img></img>”
22
Q
<div>Which enzyme is responsible for <b>elongating the DNA strand</b>? </div>
<div><br></br></div>
<div>{{c1::DNA polymerase (specifically, DNA polymerase III in <u>prokaryotes</u>)}}</div>
A
“<div><i>DNA polymerase uses <b>dNTP</b> substrates to add <b>monophosphates</b>; In the process, inorganic pyrophosphate (PPi) is given off</i></div><div><i><img></img></i></div>”
23
Q
<div><div><div><b>{{c2::DNA}} polymerase</b> <i>must</i> see a(n) {{c1::<b>RNA primer</b>}} to bind, which is <b>complementary</b> and <b>antiparallel</b> to the polymerase</div></div></div>
A
“Technically it doesn’t need to be an <u>RNA</u> primer, just any primer with a 3’-OH group (i.e. PCR)<div><img></img></div>”
24
Q
“<div><div><div><b>DNA polymerase </b>pauses and checks (““<b>proof-reads</b>””) via {{c1::3’ -> 5’ exonuclease}} activity</div><div></div></div></div>”
A
“<img></img>”
25
Which enzymes are responsible for removing the RNA primer in eukaryotes?
{{c1::RNase H and FEN-1::2}}
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*note: this is probably pretty low yield for step 1
Removal of primers
Prokaryotes: RNase H and DNA polymerase I (5'→3' exonuclease activity)
Eukaryotes: RNase H and FEN-1 (flap endonuclease-1)
Gaps between fragments are filled after primer removal
Prokaryotes : DNA polymerase I
Eukaryotes : Polymerase δ
26
Which enzyme catalyzes the formation of a phosphodiester bond between Okazaki fragments?
{{c1::DNA ligase}}
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this is the lagging strand and is synthesized in the direction away from the replication fork
27
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The enzyme which adds {{c2::TTAGGG::sequence}} to 3' ends of chromosomes to avoid loss of genetic material with every duplication is known as {{c1::Telomerase}}
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- eukaryotes only; prokaryotes have circular DNA
- critically shortening in telomere length --> signal for programmed cell death (TP53 becomes activated --> apoptosis)
28
Which replication enzyme is a RNA-dependent DNA polymerase, and thus a major example of reverse transcriptase activity, in humans?
{{c1::Telomerase}}
- endogenously expressed in cells that need to divide regularly(ex. germ cells, certain adult stem cells), allowing them to proliferate indefinitely in a controlled manner
29
Telomerase is a rare example where {{c1::reverse transcriptase::enzyme}} activity occurs endogenously in humans
This is found in eukaryotes only
30
What pathology is associated with increased telomerase activity?
{{c1::Cancer}}
>90% of cancer cells contain increased telomerase activity, allowing for continued proliferation without apoptosis
31
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{{c1::RNA}} polymerase doesn't have to see a RNA primer to bind
"binds to promoter regions and requires transcription factors![]()
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32
Which type of DNA mutation causes the least severe damage?
{{c1::Silent mutations}}
silent << missense < nonsense < frameshift
33
Which type of DNA mutation causes the most severe damage?
{{c1::frameshift mutations}}
silent << missense < nonsense < frameshift
34
A(n) {{c1::silent}} mutation occurs when a nucleotide substitution codes for the same amino acid
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often a base change in 3rd position of codon (tRNA wobble)
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A(n) {{c1::missense}} mutation occurs when a nucleotide substitution codes for a different amino acid
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e.g. sickle cell disease (substitution of glutamic acid with valine)
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A(n) {{c1::nonsense}} mutation occurs when a nucleotide substitution codes for a stop codon
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usually results in a nonfunctional protein
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A(n) {{c1::frameshift}} mutation occurs when there is a deletion or insertion of a number of nucleotides not divisible by {{c2::3}}, resulting in misreading of all nucleotides downstream
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protein may be shorter or longer, and its function may be disrupted or altered; examples include duchenne muscular dystrophy and Tay-sachs disease
38
A mutation at a(n) {{c1::splice site}} results in a retained intron in the mRNA, leading to a protein with impaired or altered function
"rare cause of cancers, dementia, epilepsy, and some types of β-thalassemia "
39
The enzyme that recognizes and excises pyrimidine dimer mutations is {{c1::excision endonuclease}}
nucleotide excision repair
40
What phase of the cell cycle do nucleotide excision repairs occur?
{{c1::G1}}
"In contrast, BER occurs in all phases of the cell cycle and Mismatch Repair occurs predominantly in S
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41
Xeroderma Pigmentosum is an inherited pathology due to a defective {{c1::Nucleotide Excision Repair}} pathway
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- This is inherited in an autosomal recessive manner
- can diagnose by measurement of repair mechanisms in WBCs
42
What form of DNA repair fixes mutations due to DNA replication errors?
{{c1::Mismatch repair}}
very important for maintaining microsatellite stability (DNA slippage can occur easily at these sites). Problems with this can lead to colon cancer
43
Recognition and facilitation of excision of {{c2::mismatched nucleotides}} occur via enzymes found on two genes: {{c1::MSH2 (MutS)}} or {{c1::MLH1 (MutL)}}
- MutS recognizes the mismatch on the newly created daughter strand (distinguished from parent strand by occasional nicks in the daughter strand phosphodiester bonds), MutL is then recruited and the complex slides along the DNA until 1 of daughter strand nicks is encountered
- exonuclease 1 is then loaded onto the repair complex and activated, which then excises the mismatch
Mutations in these genes account for 90% of cases of Lynch syndrome
44
What pathology is characterized by a deficiency of the enzymes used in mismatch base repair?
{{c1::Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC])}}
leads to colon cancer with microsatellite instability (DNA slippage can occur easily at these sites). Problems with this can lead to colon cancer
45
What phase of the cell cycle do mismatch base repairs predominantly occur?
{{c1::S}}
"- some also occur in G2; whereas NER occurs in G1 and BER occurs throughout cell cycle
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46
What form of DNA repair fixes mutations due to spontaneous/toxic deamination?
{{c1::Base excision repair}}
i.e. deamination, oxidation, etc
47
In base excision repair, base-specific {{c1::glycosylases}} remove the altered base and create a(n) {{c2::AP (apurinic/apyrimidinic)}} site
"ex. cytosine deamination is repaired with uracil glycosylase![]()
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48
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Which base excision repair enzyme is responsible for removing nucleotides at the 5' end?
{{c1::AP-endonuclease}}
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Which base excision repair enzyme is responsible for removing nucleotides at the 3' end?
{{c1::Lyase}}
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50
What phase of the cell cycle do base excision repairs occur?
{{c1::Throughout the cell cycle}}
"Whereas NER occurs in G1, and mismatch occurs predominantly in S
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51
Which forms of DNA repair repairs double-stranded breaks (due to ionizing radiation)?
{{c1::Nonhomologous end joining}} and {{c2::homologous recombination}}
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Nonhomologous End Joining depicted below
Homologous Recombination depicted below
52
Mechanisms to repair {{c1::dsDNA}} breaks are defective in Ataxia telangiectasia, Fanconi anemia, and SCID
- Due to defects in the ATM protein, FANC enzymes, and Artemis enzyme respectively
53
The {{c1::template}} strand is the dsDNA strand used for transcription; it is complementary and antiparallel to mRNA
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54
The {{c1::coding}} strand is the strand of dsDNA that is NOT used during transcription, but is identical to mRNA (substitute T/U)
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55
Practice: If a DNA template sequence is TAGC, what is the mRNA sequence?
{{c1::GCUA}}
"AUCG is wrong because the strand is built in the 5' to 3' direction "
56
The {{c1::untranslated region (UTR)}} of mRNA is the portion of mRNA which contains no protein information
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every RNA contains a 5' and 3' UTR
57
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In eukaryotes, each gene has it's own {{c1::promoter}}, to which RNA polymerase II may bind
in prokaryotes, there may be one promoter for many genes (operons)
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The promoter is an AT-rich upstream sequence with {{c1::TATA}} and {{c1::CAAT}} boxes
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- TATA (Hogness) is located approximately 25 bases upstream, CAAT is located 70-80 bases upstream
- these regions of weak A:T bonds are where RNA polymerase binds (easy to open up vs stronger G:C bonds)
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Promoters serve as binding sites for {{c1::general::general/specific}} transcription factors
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they are present in all cells with a nucleus and are involved in basal transcription
60
{{c1::Enhancers}} are stretches of DNA that increase gene expression by binding specific transcription factors
"These bind regulatory activator proteins which stabilize RNA polymerase
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{{c1::Silencers}} are sites where negative regulators (repressors) bind to DNA
These decrease expression of a gene on the same chromosome by preventing RNA polymerase from binding
62
Enhancers increase transcription via enhanced activity of the enzyme {{c1::RNA polymerase II}}
"- enhancers bind regulatory Activator proteins that stabilize transcription factors / RNA pol
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63
Enhancers serve as binding sites for {{c1::specific::specific/general}} transcription factors
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64
Are enhancers/silencers close or far from the gene it regulates?
{{c1::May be close to, far from, or within the gene (in an intron)}}
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- Because of DNA coiling, many are geometrically close but many nucleotides away from gene
- enhancer sequences can also bind activator proteins that facilitate bending of DNA
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How can enhancers be far away from the gene it regulates?
{{c1::DNA will bend to bring enhancer to promoter}}
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66
RNA polymerase {{c1::I}} makes {{c2::r}}RNA
"rRNA is the most numerous RNA; this is restricted to the Nucleolus and thus in Cancer, malignant cells with high mitotic activity have a large # of active rRNA and prominent nucleoli
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67
RNA polymerase {{c1::II}} makes {{c2::m}}RNA
"mRNA is the largest RNA; this enzyme is inhibited by the amanita phalloides (death cap mushroom) amatoxin
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68
RNA polymerase {{c1::III}} makes {{c2::t}}RNA and 5S rRNA
"tRNA is the smallest RNA![]()
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In eukaryotes, {{c2::RNA polymerase II}} may be inhibited by {{c1::α-amanitin}}
- absorbed into GI tract, amatoxins are transported to liver by portal circulation whereby active transport by organic anion transporting polypeptide (OATP) and sodium taurocholate cotransporter (NTCP) concentrate toxin within liver cells
- found in Amanita phalloides (death cap mushrooms); causes severe hepatotoxicity if ingested (6-24 hours post ingestion, abdominal pain, vomiting, and cholera like diarrhea)
70
What drug is an inhibitor of prokaryotic RNA polymerase?
{{c1::Rifampin}}
therefore, rifampin blocks prokaryotic transcription
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One co-transcriptional modification is the addition of a(n) {{c1::7-methylguanosine cap}} at the {{c2::5}}' end
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- occurs in 2 stages, adding GTP, then methylation
- capping occurs in the nucleus as RNA is being transcribed; functions as protection against cellular degradation / allow escape from nucleus
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One post-transcriptional modification is the addition of a(n) {{c1::poly-A tail}} at the 3' end
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- synthesized by poly-A polymerase in the nucleus
- protects mRNA from degradation within the cytoplasm after it exits the nucleus
73
What sequence of bases represents a polyadenylation signal?
{{c1::AAUAAA::6}}
telomeres are TTAGGG
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mRNA quality control occurs at {{c1::cytoplasmic processing bodies (P-bodies)}}, which contain exonucleases, decapping enzymes, and microRNAs
- these are involved in regulation and turnover of mRNA; particularly in translation repression and mRNA decay
- additionally, certain constituents are involved in microRNA induced mRNA silence
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mRNAs may be stored in {{c1::P-bodies}} for future translation
- typically mRNA once entering cytosol associates with ribosomes, certain mRNA associated with proteins found in P bodies
- P bodies can partake in mRNA quality control, but also act to store mRNA to later release for further translation
76
In the first step of alternative splicing, the primary transcript (hnRNA) combines with {{c1::small nuclear ribonucleoproteins (snRNPS)}} and other proteins to form the {{c2::spliceosome}}
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Anti-snRNP antibodies are known as anti-Smith antibodies (SLE)
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After the spliceosome has been formed in alternative splicing, a(n) {{c1::lariat-shaped (looped)}} intermediate is generated
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In the final step of alternative splicing, the {{c2::lariat}} is released to precisely remove the {{c1::intron}} and join two {{c1::exons}}
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Spliceosomes remove introns containing GU at the 5' splice site and AG at the 3' splice site
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Antibodies to spliceosomal snRNPs, also known as {{c2::anti-Smith}} antibodies, are highly specific for {{c1::SLE}}
Lupus
80
Different exons are frequently combined by {{c1::alternative splicing}} to produce a larger number of unique proteins
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allows for multiple, different proteins to be generated from a single gene
81
One hematological pathology that is due to abnormal splicing variants is {{c1::β-thalassemia}}
"mutation in 5' splice donor site of intron 1, therefore intron 1 is not removed
others include; Gaucher disease, Tay-Sachs Disease, Marfan syndrome
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{{c1::microRNAs}} are small, noncoding RNA molecules that post-transcriptionally regulate protein expression
"introns can contain microRNA (miRNA) genes![]()
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83
microRNA often leads to the {{c1::silencing/inactivation}} of target mRNA, thus causing {{c1::decreased}} translation into protein
can have multiple mRNA targets, typically
related to complementary base pairing
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{{c1::tRNAs}} are the smallest RNAs and have a clover-leaf structure
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At the base of a tRNA molecule is a(n) {{c1::anti-codon loop}}, which base pairs with a codon of mRNA in a complementary, antiparallel fashion
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At the {{c2::3}}' end of a tRNA molecule is a(n) {{c1::5'-CCA-3'}} sequence, which is the amino acid acceptor stem
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CCA = Can Carry Amino acids
The -OH of A links to the amino acid
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The {{c1::T-arm}} of tRNA contains the TΨC sequence (ribothymidine, pseudouridine, cytidine) necessary for tRNA-ribosome binding
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What is the function of the T-arm of tRNA?
{{c1::tRNA-ribosome binding}}
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The {{c1::D-arm}} of tRNA contains dihydrouridine residues necessary for tRNA recognition by the correct aminoacyl-tRNA synthetase
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90
Aminoacyl-tRNA synthetase requires {{c1::ATP}} and releases inorganic PPi
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scrutinizes an amino acid before and after it binds to tRNA; if incorrect, bond is hydrolyzed
91
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Accurate base pairing is usually required only in the first two nucleotide positions of a mRNA codon because codons differing in the 3rd ""{{c1::wobble}}"" position may code for the same amino acid
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Peptide bond formation is facilitated by the ribozyme {{c1::peptidyl transferase}}
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a ribozyme is RNA carrying out a catalytic reaction (enzyme is a protein)
93
What is the smaller ribosomal subunit used in prokaryotic translation?
{{c1::30s}}
this subunit recognizes the shine dalgarno sequence
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What is the total size of the ribosome used in prokaryotic translation?
{{c1::70s}}
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What is the smaller ribosomal subunit used in eukaryotic translation?
{{c1::40s}}
"this subunit recognizes the 5'-7-Methyl-G-cap "
96
What is the larger ribosomal subunit used in eukaryotic translation?
{{c1::60s}}
"this is the target of shiga toxins and verotoxin "
97
What is the total size of the ribosome used in eukaryotic translation?
{{c1::80s}}
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98
Eukaryotic {{c1::Initiation Factors}} help assemble the 40s ribosomal subunit with the initiator tRNA
"- IF's identify either the 5' cap or an internal ribosome entry site (IRES - often located in 5'-UTR); Uses GTP to assemble the structure
- initiation factors are released when the mRNA and the ribosomal 60S subunit assemble with the complex
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99
Translation is initiated by {{c1::GTP}} hydrolysis
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100
At what site of the ribosome does tRNA bind to for translation initiation?
{{c1::P site}}
"""prepare"" site- the ""peptidyl"" site![]()
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101
In the first step of strand elongation, a(n) {{c1::aminoacyl-tRNA}} binds to the A site
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102
After aminoacyl-tRNA binds to the A site of the ribosome, {{c1::peptidyl transferase}}, a ribozyme, catalyzes peptide bond formation (translation)
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103
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In the final step of translation elongation, {{c1::translocation}} of the ribosome occurs, advancing the ribosome 3 nucleotides towards the 3' end of mRNA
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requires GTP and elongation factors
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In addition to GTP, translocation of the ribosome during translation also requires eukaryotic {{c1::elongation factor 2 (eEF-2)}}
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- pseudomonas exotoxin A and diphtheria toxin act via inhibition of eukaryotic enlongation factor 2 via ADP ribosylation
- translocation occurs when Ribosome advances 3 nucleotides towards 3' end, moving the peptidyl tRNA to the P site (A site is now empty)
105
In the final step of translation, a stop codon is recognized by {{c1::release factor}} and the completed polypeptide is released from the ribosome
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106
A(n) {{c1::chaperone}} protein, is an intracellular protein involved in facilitating and/or maintaining protein {{c2::folding}}
in yeast, heat shock proteins (e.g. Hsp60) are expressed at high temperatures to prevent protein denaturing/misfolding
107
What is the shortest phase of the cell cycle?
{{c1::M phase (mitosis + cytokinesis)}}
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Which cell cycle phase is characterized by resting, non-dividing cells?
{{c1::G0}}
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What cell type remains in G0 and can only regenerate from stem cells?
{{c1::Permanent}}
examples include neurons, skeletal/cardiac muscle, and RBCs
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What cell type enters G1 from G0 when stimulated?
{{c1::Stable (quiescent)}}
examples include hepatocytes, lymphocytes, renal tubular cells, periosteal cells
111
What cell type never enters G0 and divides rapidly with a short G1?
{{c1::Labile}}
examples include bone marrow, gut epithelium, skin, hair follicles, and germ cells
112
Which cell cycle phase is characterized by DNA synthesis and replication?
{{c1::S}}
46 chromosomes/chromosomes per cell before S phase; 92 chromatids per cell after S phase (still 46 chromosomes)
113
Which cell cycle phase(s) are part of interphase?
{{c1::G1, S, G2}}
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- G1 - cells in this phase prepare building blocks for DNA synthesis (synthesis of RNA, protein, lipid, and carbs)
- S - DNA replication occurs during this phase
- G2 - DNA is checked for errors and corrections are made if possible, if corrections cannot be made, then apoptosis will result; ATP synthesis occurs here
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Which cell cycle phase(s) are NOT part of interphase?
{{c1::M}}
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115
{{c1::Free}} ribosomes are unattached to any membrane and are the site of synthesis for cytosolic and organellar proteins
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What part of the cell is the site of steroid synthesis and detoxification of drugs and poisons?
{{c1::Smooth endoplasmic reticulum}}
liver hepatocytes and steroid hormone-producing cells of the adrenal cortex and gonads are rich in SER
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When proteins are misfolded, multiple {{c1::ubiquitins}} are added, which aids in trafficking to the proteasome
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The {{c1::proteasome}} is a barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins
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119
Defects in the ubiquitin-proteasome system have been implicated in some cases of {{c1::Parkinson}} disease
defects in the Parkin, PINK1, and DJ-1 genes specifically
120
On the N terminal side of newly synthesized protein, a stretch of 10-15 hydrophobic amino acids forms the {{c1::N-terminal signal}} sequence
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The N-terminal signal sequence of a newly synthesized protein is bound by a(n) {{c1::signal recognition particle (SRP)}}, which attaches the complex to the {{c2::ER}} membrane
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once the SRP-protein complex is bound to the ER, the signal sequence is removed and the protein enters the ER (co-translational)
122
Which enzyme phosphorylates mannose in the Golgi apparatus, facilitating protein trafficking?
{{c1::Phosphotransferase}}
specifically, N-acetylglucosaminyl-1-phosphotransferase
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What pathology is associated with a defect in the enzyme N-acetylglucosaminyl-1-phosphotransferase?
{{c1::I-cell disease (inclusion cell disease/mucolipidosis type II)}}
failure of the Golgi to phosphorylate mannose residues (i.e. mannose-6-phosphate) on glycoproteins
124
{{c1::Endosomes}} are sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use
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Which inherited lysosomal storage disorder is characterized by coarse facial features, clouded corneas, and restricted joint movement with high serum levels of multiple lysosomal enzymes?
{{c1::I-cell disease}}
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- often fatal in childhood (typically due to severe dilated cardiomyopathy)
126
I-cell disease is characterized by high plasma levels of {{c1::lysosomal}} enzymes
proteins are secreted extracellularly rather than delivered to lysosomes
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Which vesicular trafficking protein is responsible for retrograde Golgi transport (cis-Golgi and ER) and intra-Golgi transport?
{{c1::COPI}}
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Normally, Proteins are made at the ER, packaged / modified in the Golgi, and then routed to different locations (lysosomes, secretory vesicles, plasma membrane)
COPI aids in taking proteins that are packaged / modified in the golgi and sending them back to the ER for use there, or to another spot on the golgi apparatus
128
Which vesicular trafficking protein is responsible for anterograde Golgi transport (ER to cis Golgi)?
{{c1::COPII}}
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129
Which vesicular trafficking protein is responsible for transport between the trans-Golgi and lysosomes?
{{c1::Clathrin}}
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130
Which vesicular trafficking protein is responsible for transport between the plasma membrane and endosomes (receptor-mediated endocytosis)?
{{c1::Clathrin}}
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131
Which type of filament is predominantly involved in maintainence of cell structure?
{{c1::Intermediate filaments (e.g. desmin, cytokeratin)}}
other examples include vimentin, lamins, glial fibrillary acid proteins (GFAP), and neurofilaments
132
Which type of filament is predominantly involved in movement and cell division?
{{c1::Microtubules (e.g. cilia, flagella)}}
other examples include mitotic spindles, axonal trafficking, and centrioles
133
What type of filament are cilia and flagella?
{{c1::Microtubule}}
"In contrast, villi are actin filaments
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134
{{c1::Microtubules}} are a cylindrical outer structure composed of a helical array of polymerized heterodimers of {{c2::α-}} and {{c2::β-tubulin}}
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135
Each α- and β-tubulin heterodimer of a microtubule has 2 {{c1::GTP}} bound
GDP bound tubulin will dissociate
136
Which molecular motor protein is responsible for retrograde transport to the microtubule (+ to -)?
{{c1::Dynein}}
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137
Which molecular motor protein is responsible for anterograde transport to the microtubule (- to +)?
{{c1::Kinesin}}
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138
{{c1::Cilia}} are organized in a(n) {{c2::9+2}} arrangement of microtubule doublets
"
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Flagella as well;
139
The base of a cilium below the cell membrane, called the {{c1::basal body}}, consists of 9 microtubule triplets with no central microtubules
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140
Axonemal {{c2::dynein}} is a(n) {{c1::ATPase}} that links peripheral 9 doublets and causes bending of cilium (movement)
"Coordinated ciliary beating is facilitated by gap junctions
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141
{{c1::Kartagener}} syndrome is a(n) {{c3::autosomal recessive::inheritance}} disease characterized by immotile cilia due to a(n) {{c2::dynein arm}} defect
also known as primary ciliary dyskinesia; dynein is important for cilia function, thus anything that requires cilia will be dysfunctional (organogenesis, mucociliary tract, fallopian tubes)
142
Kartagener syndrome results in decreased male and female {{c1::fertility}}
due to immotile sperm and dysfunctional fallopian tube cilia, respectively
143
Which developmental pathology is characterized by bronchiectasis, recurrent sinusitis, and situs inversus?
{{c1::Kartagener syndrome}}
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an example of situs inversus is dextrocardia on CXR
144
What is the most abundant protein in the human body?
{{c1::Collagen}}
extensively modified by post-translational modification
145
What type of collagen is the most common (90%)?
{{c1::Type I}}
- Found in Bone, Skin, Tendon, Ligaments, Dentin, Fascia
146
What type of collagen makes up bone, skin, and tendon?
{{c1::Type I}}
also makes up dentin, fascia, cornea, and is part of late wound repair
this is defective in Osteogenia Imperfecta
147
What type of collagen makes up cartilage?
{{c1::Type II}}
also makes up the vitreous body, pubic symphysis, nucleus pulposus
Autoantibodies to type II collagen can be seen in patients with relapsing polychondritis
148
What type of collagen makes up skin and blood vessels?
{{c1::Type III}}
- Also makes up uterus, fetal tissue (growing fetus need to be able to stretch), granulation tissue
- defective in Vascular Ehlers Danlos
149
What type of collagen makes up reticulin fibers?
{{c1::Type III}}
This is a very pliable structure
150
What type of collagen makes up the basement membrane?
{{c1::Type IV}}
also makes up the basal lamina and lens
151
The {{c3::vascular}} type of Ehlers-Danlos Syndrome that is caused by a deficiency of type {{c4::III}} collagen can lead to:
- the formation and rupture of {{c1::aneurysms}}
- rupture of organs (ex. in women the {{c2::uterus::specific organ}} during birth)
- Both Berry and Aortic Aneurysms
- Pregnant patients with vascular Ehlers-Danlos can rupture their Uterus
152
What type of collagen is decreased in osteogenesis imperfecta type I?
{{c1::Type I}}
- collagen is normal but production is decreased
- type I collagen is the predominant collagen in osteoid (organic portion of bone matrix)
153
What pathology is characterized by a defective type IV collagen?
{{c1::Alport syndrome}}
- Cant See (Lens)
- Cant Pee (Basement membrane of the Glomerulus)
- Cant Hear a Bee (Cochlea)
154
Type {{c1::IV}} collagen is targeted by autoantibodies in {{c2::Goodpasture}} syndrome
specifically, the alpha 3 chain of type IV collagen is targeted
- found in lungs (hemoptysis) and glomeruli (GBM)
155
Collagen is a repeat of a tripeptide following the pattern {{c1::Gly-X-Y}}, made by fibroblasts
- X and Y are usually proline or lysine
- also have signal molecules
156
One third of the collagen strand is made of the amino acid {{c1::glycine}}
glycine has the smallest side chain, therefore easy to form a triple helix (very little steric hindrance)
157
In the first step of collagen synthesis, translation of collagen alpha chains forms {{c1::preprocollagen}}
"
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- Collagen mRNA is first translated in the RER to preprocollagen
- Signal molecules direct it into the ER lumen, and the structure is now the ""Pro-Alpha chain""
158
Collagen Synthesis: After the collagen alpha chains are synthesized, specific residues of the amino acids {{c1::proline}} and {{c1::lysine}} are {{c2::hydroxylated}}
"This step requires Vitamin C (deficient in Scurvy)
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159
Collagen Synthesis: Hydroxylation of selected prolines and lysines during collagen synthesis requires vitamin {{c1::C}}
"deficiency of vitamin C causes scurvy as these patients will have defective pro-alpha chains that can't form a triple helix, resulting in collagen being degraded instead of secreted"
160
Collagen Synthesis: Following hydroxylation of proline and lysine, there is {{c1::glycosylation}} of pro-α-chain {{c2::hydroxylysine}} residues
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161
Collagen Synthesis: After hydroxylation and glycosylation, hydrogen and disulfide bonds help form a(n) {{c1::triple helix}} of collagen α chains (procollagen)
"
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problems forming the triple helix may be indicative of osteogenesis imperfecta - glycine is swapped out with a bulkier amino acid causing steric hindrance that makes a faulty triple helix structure for type I collagen
162
Collagen Synthesis: After the triple helix is formed, the procollagen is {{c1::exocytosed}} into the extracellular space
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163
Where in the cell does synthesis, hydroxylation, and glycosylation of preprocollagen occur?
{{c1::Rough endoplasmic reticulum}}
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164
Collagen Synthesis: Once in the extracellular space, cleavage of disulfide-rich terminal regions of procollagen by {{c2::procollagen peptidase}} forms the insoluble {{c1::tropocollagen}}
"
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These are individual triple helix alpha chain molecules that haven't been crosslinked at this point
problems with cleavage of procollagen to tropocollagen due to defects in procollagen peptidase result in Ehlers-Danlos
165
Collagen Synthesis: Staggered tropocollagen molecules are reinforced by covalent {{c1::lysine-hydroxylysine}} {{c2::cross-linkages}} to make collagen fibrils
"
- Collagen fibrils self assemble to form Collagen Fibers
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- this step is catalyzed by Lysyl oxidase and is deficient in Menkes disease
166
Formation of lysine-hydroxylysine cross-linkages (collagen synthesis) requires both {{c1::copper}} and the enzyme {{c1::lysyl oxidase}}
"copper deficiency leads to Menkes disease
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167
Where in the cell does the synthesis and formation of tropocollagen and collagen fibrils occur?
{{c1::Extracellular space}}
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168
Which collagen synthesis pathologies are associated with problems with cross-linking?
{{c1::Ehlers-Danlos syndrome, Menkes disease::2}}
- Ehlers-Danlos is problems with proteolytic cleavage (deficiency in procollagen propeptidase) to generate the insoluble tropocollagen substrate from procollagen
- Menkes Disease results in copper deficiency (resulting in a dysfunctional Lysyl Oxidase), making it impossible to cross link tropocollagens into collagen fibrils
169
Which collagen synthesis pathologies are associated with problems forming the triple helix?
{{c1::Osteogenesis imperfecta and Scurvy}}
"
-in osteogenesis imperfecta; Deficient Type 1 Collagen replaces Glycine with a bulky amino acid, creating steric hindrance that prevents 3 pro-alpha chains from properly linking into the triple helix procollagen; This improper collagen structure is either destroyed in the fibroblast, or is faultily incorporated into bone with hydroxyapatite causing brittleness
In scurvy, These patients can't hydroxylate pro-alpha chains (hydroxylation of proline or lysine requires vit C), thus they can't form the triple helix and the nascent collagen is degraded in the cell without being secreted
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170
Osteogenesis imperfecta is most commonly caused by gene defects in {{c1::COL1A1}} and {{c1::COL1A2}}
- COL1 = type 1 collagen, type 1 collagen is the predominant collagen in osteoid, which allows the bone to be somewhat flexible while maintaining strength
171
What is the inheritance of osteogenesis imperfecta (most common)?
{{c1::Autosomal dominant}}
with decreased production of otherwise normal type 1 collagen
172
Osteogenesis imperfecta is characterized by multiple recurrent {{c1::fractures}} with minimal trauma
"
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treat with bisphosphonates to reduce fracture risk
may occur during the birth process; can mimic child abuse, but bruising is absent
173
{{c2::Osteogenesis imperfecta}} may present with {{c1::blue sclerae}} due to translucent connective tissue over choroidal veins
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174
Osteogenesis imperfecta may present with {{c1::hearing loss}} due to abnormal ossicles
bones of the middle ear fracture easily
175
Some forms of osteogenesis imperfecta have tooth abnormalities, including opalescent teeth that wear easily due to lack of {{c1::dentin}}
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this is known as dentinogenesis imperfecta
176
The {{c1::classical}} type of Ehlers-Danlos syndrome (joint and skin symptoms) is caused by a mutation in type {{c2::V}} collagen
the classical type includes Ehlers-Danlos types 1 & 2
177
What type of Ehlers-Danlos syndrome is the most common type?
{{c1::Hypermobility type (joint instability)}}
this is also known as Ehlers-Danlos type 3
178
Ehlers-Danlos syndrome is characterized by faulty collagen synthesis causing {{c1::hyperextensible}} skin
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179
Ehlers-Danlos syndrome is characterized by faulty collagen synthesis causing {{c1::hypermobile}} joints
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180
The classical and vascular forms of Ehlers-Danlos syndrome are inherited in a(n) {{c1::autosomal dominant}} manner
However, other types of Ehlers-Danlos can be inherited in Autosomal Recessive manner; remember the classical and vascular forms involve structural proteins
181
What is the inheritance of Menkes disease?
{{c1::X-linked recessive}}
Menkes. Men are more likely to get it
182
What gene is defective in Menkes disease?
{{c1::ATP7A}}
not to be confused with ATP7B (Wilson disease)
183
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{{c2::Menkes}} disease results in {{c1::brittle, ""kinky""}} hair, growth retardation, and hypotonia
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184
{{c1::Elastin}} is a stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords, and ligamentum flava
"- dominant elastic protein in the arteries, makes up 50% of aortic tissue
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- Ligamentum flava has lots of elastin, allowing it to connect vertebrae to allow relaxed and stretched conformations
185
Elastin is rich in non-hydroxylated {{c1::proline}}, {{c1::glycine}}, and {{c1::lysine}} residues (amino acids)
"In comparison to collagen
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- mostly non-hydroxylated amino acids (some hydroxyproline, no hydroxylysine)
- no glycosylation (surrounding network of fibrillin microfibrils)
- elastin is secreted as tropoelastin, whose unique polypeptide backbone when cross linked causes random coiling (giving it its elastic property)
186
Elastin is tropoelastin with {{c1::fibrillin}} scaffolding
"- Elastin has an unusual polypeptide backbone that causes random coiling when crosslinked - giving it it's elastic properties
"
- central core of tropoelastin has two unique amino acids that crosslink and provide stability
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187
"
What gives elastin its elastic ""rubber-like"" properties?
{{c1::Cross-linking}}
"
"
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- mediated by lysyl oxidase which deaminates lysine residues of tropoelastin, facilitating formation of desmosine cross-links
- allows for elastin fibers to be stretched to several times original length and then recoil once stretching forces are withdrawn
188
Where in the cell does cross-linking of elastin take place?
{{c1::Extracellular space}}
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189
{{c1::Wrinkles}} of aging are due to decreased {{c2::collagen}} and elastin production
"decreased collagen production and increased collagenases secondary to UV-A radiation induced inflammatory damage ![]()
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190
Gel electrophoresis separates fragments on the basis of {{c1::size}}
all DNA/RNA/protein fragments used are negatively charged
191
When using blotting procedures, the {{c1::probe}} determines what sequences are detected
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the probe is complementary to the gene sequence of interest
192
A(n) {{c2::Southern}} blot is used to analyze {{c1::DNA}}
"Used in genetic testing of diseases, forensics (DNA identification - microsatellite analysis can also be used here)
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Can use to observe inheritance of RFLP markers
193
A(n) {{c2::Northern}} blot is used to analyze {{c1::RNA}}
measure mRNA levels (gene expression)
194
Does a Southern blot require gel electrophoresis before analysis?
{{c1::Yes}}
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195
What type of probe is used to bind protein when using a Western blot?
{{c1::Labeled antibody}}
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binds protein that has been separated by gel electrophoresis and transferred to a membrane
196
What type of probe is used to bind DNA/RNA when using a Southern/Northern blot?
{{c1::Labeled single stranded DNA / RNA oligonucleotide}}
"This can be radioactive or fluorescently labeled
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197
The {{c1::Western}} blot *used to be* the confirmatory test for HIV after a positive ELISA
"FA 2019: Western blot tests are no longer recommended by the CDC for confirmatory testing. Presumptive diagnosis is made with HIV-1/2 Ag/Ab immunoassays. These assays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2."
198
Does a Dot (slot) blot require gel electrophoresis before analysis?
{{c1::No!}}
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useful for analyzing DNA, RNA, or protein but must know the specific mutation being looked for; e.g. Hemochromatosis (person #3 is homozygous mutant for the C282Y mutation)
199
A(n) {{c1::Southwestern}} blot is used to identify {{c2::DNA-binding}} proteins using labeled oligonucleotide probes
"useful for identifying transcription factors "
200
In the first step of PCR, DNA is {{c1::denatured}} by using {{c2::heat}} to separate the strands
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temperature is approximately 95° C
201
In the second step of PCR, {{c2::DNA primers}} {{c1::anneal}} to specific sequences on each DNA strand to be amplified
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temperature is approximately 55° C
202
In the final step of PCR, heat-stable {{c2::Taq DNA polymerase}} {{c1::elongates}} the DNA sequence following each primer
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temperature is approximately 72° C
203
What type of primer is used in a polymerase chain reaction (PCR)?
{{c1::DNA primer}}
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in the body, RNA primers are used; in the test tube, DNA primers are used
204
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Which end of the DNA strand does the DNA primer bind to during PCR?
{{c1::3' end}}
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205
PCR requires the addition of all four {{c1::deoxynucleotide triphosphates (dNTPs)}} for DNA synthesis
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also requires DNA polymerase and primers ; PCR is repeated until DNA sample size is sufficient
206
{{c1::Flow cytometry}} is a laboratory technique used to assess size, granularity, and protein expression of individual cells in a sample
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commonly used in the workup of hematologic abnormalities and immunodeficiencies
207
In flow cytometry, cells are tagged with {{c1::antibodies}} specific to surface or intracellular proteins
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208
In flow cytometry, antibodies are tagged with a unique {{c1::fluorescent dye}}, which is detected and counted during analysis
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209
"
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Flow Cytometry Example: Cells in the right lower quadrant are CD3{{c1::-}} and CD8{{c1::+}}
all CD8 expressing cells also express CD3, hence why this quadrant is empty
210
{{c1::Microarrays}} analyze thousands of nucleic acid sequences arranged in grids on glass or silicon
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useful for genotyping, clinical genetic testing, forensic analysis, cancer mutations, and genetic linkage analysis
211
{{c1::Microarrays}} are a laboratory technique used to profile gene expression levels of thousands of genes simultaneously to study certain diseases and treatments
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212
Microarrays use a(n) {{c1::labeled DNA/RNA}} probe, which is hybridized to the chip, and a scanner detects the relative amounts of complementary binding
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213
What two types of variations in DNA are detected when using microarrays? (DNA markers)
{{c1::
- Single nucleotide polymorphisms (SNPs)
- Copy number variations (CNVs)
}}
disadvantage: cannot detect translocation or inversions, only can detect gain or loss of material
214
"
{{c1::Enzyme-linked immunosorbent assay (ELISA)::not Coombs}} is an immunologic test used to detect the presence of either a specific antigen or antibody in a patient's blood sample
"
major ELISA variations include direct, sandwich, and competitive; can have high sensitivity and specificity
215
When using ELISA, detection involves the use of a(n) {{c1::antibody}} linked to a(n) {{c2::enzyme}}
"
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added substrate then reacts with enzyme, producing a detectable signal (e.g. color change)
216
{{c1::Fluorescence in situ hybridization (FISH)}} uses a fluorescent DNA/RNA probe to bind to a specific gene of interest on chromosomes
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217
{{c1::Fluoresence in situ hybridization (FISH)}} is a laboratory technique used for specific localization of genes and direct visualization of chromosomal anomalies
**vs Karyotyping it is higher resolution and can be done in interphase
218
A(n) {{c1::microdeletion}} is detected with FISH as no fluorescence on a chromosome compared to fluorescence at the same locus on the second copy of that chromosome
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219
A(n) {{c1::translocation}} is detected with FISH as fluorescence outside the original chromosome
"white arrows in image [A] show fragments of chromosome 17 that have been translocated to chromosome 19
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220
A(n) {{c1::duplication}} is detected with FISH as an extra site of fluorescence on one chromosome relative to its homologous chromosome
"Can result in a trisomy or tetrasomy (blue arrows in image [A])
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221
What protein is defective in Marfan syndrome?
{{c1::Fibrillin (scaffold for elastin)}}
"connective tissue disorder affecting skeleton, heart, and eyes ![]()
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222
What pathology is associated with long, tapering fingers and toes (arachnodactyly) and subluxation of lenses?
{{c1::Marfan syndrome}}
"other findings include tall with long extremities, pectus carinatum or excavatum, hypermobile joints, and cystic medial necrosis of the aorta ![]()
"
223
Marfan syndrome typically presents with subluxation of the lenses {{c1::upward::direction}} and {{c1::temporally::direction}}
versus homocystinuria which is usually downward and inward
224
Marfan syndrome is associated with a floppy {{c1::mitral}} valve
also associated with aortic incompetence and dissecting aortic aneurysms
225
What is the mode of inheritance of Marfan syndrome?
{{c1::Autosomal dominant}}
chromosome 15
missense=dominant
226
What class of diseases is Huntington disease a part of?
{{c1::Trinucleotide repeat expansion diseases}}
Try (trinucleotide) hunting for my fried eggs (X)
227
What class of diseases is Friedreich ataxia a part of?
{{c1::Trinucleotide repeat expansion diseases}}
Try (trinucleotide) hunting for my fried eggs (X)
228
The influx of calcium during the plateau phase of a myocardial action potential triggers release of Ca2+ from the {{c1::sarcoplasmic reticulum}}, causing myocyte {{c2::contraction}}
Ca2+-induced Ca2+ release
229
A defect in left-right dynein during heart morphogenesis can result in {{c1::dextrocardia}}
e.g. Kartagener syndrome (primary ciliary dyskinesia)
230
In the {{c1::peroxisome}}, ethanol may be converted to acetaldehyde via the enzyme {{c2::catalase}}
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231
Cystic fibrosis most commonly occurs due to a(n) {{c2::in-frame}} deletion of {{c1::Phe508}}
"- This results in a impaired post translational processing: improper folding and glycolyslation of CFTR results in misfolded protein that gets retained in the RER and marked for proteasomal degradation
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- thus there is decreased CFTR transported to the cell membrane; decreased Cl secreted at mucosal epithelium, decrease Cl reabsorbed at sweat glands
232
Following binding of LDL to its LDL receptor, the ligand-receptor complex is endocytosed in {{c1::clathrin}}-coated pits
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233
The LDL-containing clathrin-coated pits fuse with {{c1::lysosomes}}, which break down cholesterol ester into cholesterol
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via the enzyme lysosomal esterase
234
Sickle cell anemia occurs due to a point mutation that substitutes {{c1::glutamic acid}} (hydrophilic) with {{c1::valine}} (hydrophobic)
"glutamic acid (HbA) is negatively charged; valine (HbS) is neutral "
235
{{c1::Paroxysmal nocturnal hemoglobinuria}} may be confirmed via {{c3::flow cytometry}}, which detects a lack of CD-{{c2::55}} and CD-{{c2::59}}
"DAF and MIRL![]()
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236
Aplastic anemia may be caused by {{c2::Fanconi}} anemia, which occurs due to a(n) {{c1::dsDNA repair}} defect, resulting in bone marrow failure
"- defect in homologous recombination (double stranded break repair)
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- dsDNA breaks can be detected by the FA Core Complex, acting as a nidus to recruit BRCA repair enzymes
237
The {{c3::cell body}} and {{c3::dendrites}} of a neuron can be seen histologically with {{c1::Nissl}} staining, which stains {{c2::RER}}
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RER is not present in the axon
238
Lynch syndrome and some sporadic colorectal carcinomas arise via the {{c1::microsatellite}} instability pathway
i.e. the serrated polyp pathway
239
The {{c2::microsatellite}} instability pathway of colorectal cancer is characterized by mutations or methylation of {{c1::mismatch repair}} genes
e.g. MLH1, MSH2
240
Free radicals cause cellular injury via {{c1::peroxidation}} of lipids and {{c2::oxidation}} of DNA and proteins
DNA damage is implicated in aging and oncogenesis
241
During phagocytosis, pseudopods extend from leukocytes to form {{c1::phagosomes}}, which are internalized and merged with {{c2::lysosomes}}
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thus producing a phagolysosome
242
{{c2::Ataxia-Telangiectasia}} is due to defects in the {{c1::ATM}} gene
failure in nonhomologous end joining
243
Which immunodeficiency is caused by failure to repair DNA double strand breaks?
{{c1::Ataxia-telangiectasia}}
results in unrestricted cell cycle progression (resulting in mutations accumulating) and DNA hypersensitivity to ionizing radiation
VDJ recombination requires double strand breaks to occur, without ATM these are hard to repair (resulting in a weakened immune system)
244
"
Ataxia-TelangiectasiA presents with a triad of:
- {{c1::cerebellar defects (Ataxia)}}
- {{c2::spider angiomas (Telangiectasia)}}
- {{c3::IgA deficiency}}
"
lymphopenia and cerebellar atrophy
- Toddlers wobble and sway when walking (almost appear drunk)
- patients present also with slurred distorted speech, swallowing, dysarthria, and oculomotor apraxia
- Telangiectasias erupt on skin and eye, early aging (premature greying of hair)
245
What type of tissue is comprised of stem cells that can continuously cycle to regenerate tissue?
{{c1::Labile}}
e.g. small and large bowel, skin, bone marrow
246
{{c1::Duchenne}} muscular dystrophy is typically due to frameshift or non-sense mutations, resulting in a truncated or absent dystrophin protein
"""Duchenne = Deleted Dystrophin"" (vs. Becker, where dystrophin is mutated) "
247
{{c1::Liposarcoma}} is a malignant tumor of adipose tissue
characterized histologically by nuclear indentations and scalloping of the nuclear membrane
248
{{c1::Ubiquitin}}-ation of proteins recruits the {{c2::proteasome}} to degrade them
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249
Irinotecan, a(n) {{c2::Topoisomerase I}} inhibitor, is used to treat {{c1::Colon}} Cancer
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250
Vinca Alkaloids are antineoplastics that prevent cell cycle progression at the {{c2::M}} phase
"ex. include Vinblastine and Vincristine![]()
"
251
A general rule of chemotherapeutic side effects is that they will affect all {{c1::rapidly}} dividing cells
These are known as Labile cells; thus side affects at the skin, GI tract, bone marrow
252
Growth Factors induce cellular {{c1::growth}}
vs mitogen
- Examples include EGF, IGF-1, NGF
253
The Cell Cycle is regulated by Cyclins and Cyclin-Dependent Kinases (CDKs) which when {{c2::complexed}} allow cells to bypass {{c1::restriction points (checkpoints)}}
"- Thus, these proteins are an important point of regulation by the cell in order to avoid tumorigenesis
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- restriction points occur near the end of G1, near the end of G2, and within M metaphase
254
The G1 restriction point of the cell cycle is regulated by the tumor suppressors {{c1::p53}} and {{c1::Rb}}
"
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This allows the cell to verify:
- should I be going into S phase?
- would I be carrying any mutations into S phase?
255
p53 restricts the cell cycle to G1 by engendering the inhibition of {{c2::CDK4}}, maintaining the {{c1::hypo}}phosphorylated state of Rb
"However when stimulated, CDK4 binds Cyclin D1 to initiate the hyperphosphorylation of Rb (**this leads to Rb leaving and E2F acting as a transcription factor for things needed in S phase)
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256
In response to DNA damage, p53 initially attempts to {{c1::halt}} the cell cycle and facilitates the activity of {{c2::DNA repair}} enzymes
*bonus-what does it induce that inhibits the cell cycle?
"- induces P21 which inhibits CDK complexes important for release of E2F from RB
- facilitates NER, BER, Mismatch Repair, dsDNA repair pathways
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257
If DNA repair is not possible, p53 induces {{c1::apoptosis}}
"![]()
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258
Growth Factors stimulate G1 phase by increasing the levels of the {{c1::Cyclins}}
"- Once cyclins (ex Cyclin D1) reach a sufficient level, these activate CDKs to stimulate progression past the G1 restriction point
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- growth factors include EGF, PDGF, EPO
259
Once levels of Cyclins reach an appropriate level, these complex with {{c1::Cyclin-Dependent Kinases}} to hyperphosphorylate Rb
"- Cyclin D / CDK4 monophosphorylate Rb, which is followed by hyperphosphorylation by Cyclin E / CDK2
- this causes a conformational change that releases sequestered E2F from Rb
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260
Tumor suppressor genes {{c1::regulate}} cell growth
"- These decrease (""suppress"") risk of tumor formation (ex. p53 / Rb)
- as opposed to proto-oncogenes which promote cell growth
"
261
When performing Immunohistochemistry; a(n) {{c1::Cytokeratin}} stain can be used to identify Epithelial tumors (ex Squamous Cell Carcinoma)
"
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- ex. SCC of the head and neck, cervical cancer, lung, skin, esophagus
262
When performing Immunohistochemistry; a(n) {{c1::Vimentin}} stain can be used to identify Sarcomas, Endometrial Carcinoma, RCC, Meningioma
"These are tumors of mesenchymal tissue
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"
263
When performing Immunohistochemistry; a(n) {{c1::Desmin}} stain can be used to identify Rhabdomyosarcomas, Leiomyomas, Leiomyosarcomas
"These are tumors of muscle tissue
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264
When performing Immunohistochemistry; a(n) {{c1::Glial Fibrillary Acidic Protein (GFAP)}} stain can be used to identify Astrocytomas, Glioblastomas, Oligodendrogliomas, Ependymomas
"
These are tumors of neuroglia
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265
When performing Immunohistochemistry; a(n) {{c1::Neurofilament}} stain can be used to identify neuroblastomas, medulloblastomas, retinoblastomas
"These are tumors of neurons
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266
Colchicine works by inhibiting intracellular {{c1::microtubule}} polymerization through binding and stabilizing {{c1::tubulin}}
"
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- this prevents polymerization of microtubules, thus cells that rely on microtubule polymerization (ex Neutrophils) will be strongly affected
267
The exotoxin Diphtheria toxin causes {{c2::ADP-ribosylation (and therefore inhibition)}} of {{c2::elongation factor-2 (EF2)}}
"EF2 is needed for protein synthesis, therefore protein synthesis is inhibited by the exotoxin![]()
"
268
Diagnosis of HIV *previously* was made initially with {{c1::ELISA}}; positive results are confirmed with a(n) {{c2::Western}} blot
"FA 2019: Western blot tests are no longer recommended by the CDC for confirmatory testing. Presumptive diagnosis is made with HIV-1/2 Ag/Ab immunoassays. These assays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2.
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269
{{c1::PCR}} is the gold standard used in the diagnosis of Herpes Simplex Virus
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270
Colchicine binds {{c1::tubulin}}, preventing polymerization of {{c2::microtubules}}
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271
Which gout drug binds tubulin and inhibits intracellular microtubule polymerization?
{{c1::Colchicine}}
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thus inhibiting neutrophil entry and inflammation due to MSU crystal deposition
272
What *used to be* the rule out test for HIV?
{{c1::ELISA}}
"
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FA 2019: Western blot tests are no longer recommended by the CDC for confirmatory testing. Presumptive diagnosis is made with HIV-1/2 Ag/Ab immunoassays. These assays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2.
sensitive (SNout)
273
{{c2::Ionizing}} radiation results in the formation of double-stranded breaks in DNA and {{c1::hydroxyl free radicals}} which damage DNA
"H2O in tissues hit with ionizing radiation -> *OH free radicals generated
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associated with AML, CML, and papillary thyroid carcinoma
274
{{c1::Xeroderma pigmentosum}} results from lack of excision endonuclease activity to remove pyrimidine dimers
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defective nucleotide excision repair
275
{{c1::Sarcoma}} implies the cancer is of mesenchymal origin
soft tissues (e.g. fat, musle, bone, etc)
276
Li-Fraumeni syndrome is characterized by multiple malignancies at a(n) {{c1::early}} age
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277
Which enzyme is inhibited by topotecan?
{{c1::topoisomerase I}}
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278
Which enzyme is inhibited by irinotecan?
{{c1::topoisomerase I}}
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279
Which of the cytotoxic microtubule inhibitors bind β-tubulin and inhibit polymerization?
{{c1::Vincristine; Vinblastine::2}}
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thus preventing mitotic spindle formation
280
Which of the cytotoxic microtubule inhibitors prevent mitotic spindle formation?
{{c1::Vincristine; Vinblastine}}
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via binding to β-tubulin and inhibit its polymerization
281
Which phase of the cell cycle do vincristine and vinblastine act at?
{{c1::M phase}}
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prevent mitotic spindle formation (specifically the prophase of mitosis)
282
Which of the cytotoxic microtubule inhibitors bind microtubules and inhibit their depolymerization?
{{c1::Paclitaxel (taxanes)}}
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283
Which of the cytotoxic microtubule inhibitors enhance mitotic spindle formation?
{{c1::Paclitaxel (taxanes)}}
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284
Which phase of the cell cycle does paclitaxel (taxanes) act at?
{{c1::M phase}}
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285
Which antifungal works by disrupting mitotic spindles?
{{c1::Griseofulvin}}
"
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286
{{c1::Mesenchyme}} is the embryonic connective tissue
- not found in adults except for mesenchymal stem cells
- mostly derives from mesoderm
287
The Mesenchyme gives rise to most {{c1::connective tissue}}
- bones, cartilage, lymphatic, and circulatory systems
- cells of the mesenchyme are surrounded by protein and fluid
288
Patients with Xeroderma Pigmentosum often present with freckled and dry skin, extreme {{c1::sunlight}} sensitivity, and {{c2::corneal}} ulcers
"- patients will typically be light skinned
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289
Patients with xeroderma pigmentosum are at risk for which type/s of skin cancer?
{{c1::All :)}}
- Melanoma, Basal Cell Carcinoma, Squamous Carcinoma
290
Patients with Xeroderma Pigmentosum cannot repair {{c1::Thymidine Dimers}} formed as a result of UV-B exposure
"
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These patients either have a defective enzyme that recognizes helix distortions (XPC / XPA) or have a defective excision endonuclease (XPB, XPD-XPG)
291
Nonhomologous End Joining (NHEJ) occurs {{c1::before::before/after?}} S phase of the cell cycle
"- There is NO requirement for homology
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292
Is Nonhomologous End Joining error prone?
{{c1::Yes}}
HIGHLY error prone; this has no template strand to compare to
293
Nonhomologous End Joining is defective in {{c1::SCID}} and {{c2::Ataxia Telangiectasia}}
"- Ex. defect in the Artemis protein or ATM
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294
The intermediate filament Cytokeratin is found in {{c1::Epithelial}} cells
"- Thus IHC stains can be developed for tumors of epithelial cells
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- Keratin proteins are highly abundant in exposed stratified squamous epithelium (such as epidermis, oral mucosa) and are less abundant but still present in simple epithelium (such as liver, gut, pancreas)
295
The intermediate filament Vimentin is found in {{c1::mesenchymal}} tissue
"
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(ex fibroblasts, endothelial cells, macrophages)
- Thus IHC stains can be developed for tumors of mesenchymal origin
- endogenously, Vimentin's role is to maintain cell structure in mesenchymal cells
296
The intermediate filament Desmin is found in {{c1::muscle}} cells
"- Thus IHC stains can be developed for tumors of muscle cells
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- endogenously, Desmins role is to maintain cell structure in muscle cells (Smooth, cardiac, skeletal)
297
The intermediate filament Glial Fibrillary Acidic Protein (GFAP) is found in {{c1::neuroglial}} cells (ex. astrocytes, Schwann cells, oligodendrocytes)
"- Thus IHC stains can be developed for tumors of neuroglial cells; do not rely on this for schwannoma as it also has S-100
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- endogenously, GFAPs role is to maintain cell structure in Neuroglia
298
The intermediate filament Neurofilament is found in {{c1::neurons}}
- Thus IHC stains can be developed for tumors of neurons (ex. Neuroblastoma)
- endogenously, Neurofilaments role is to maintain cell structure in neurons
299
The Peroxisome is a cytosolic membrane involved in the β-oxidation of {{c1::Very-long-chain fatty acids (VLCFA)}}
- this is defective in Adrenoleukodystrophy - VLCFA build up and cause pathology
300
Which cellular organelle is responsible for catabolism of branched-chain fatty acids, amino acids, and ethanol?
{{c1::Peroxisome}}
An example of a branched-chain fatty acid = Phytanic Acid
301
A germline P53 mutation predisposes you to what tumor syndrome?
{{c1::Li-Fraumeni (SBLA) Syndrome}}
When patients develop a somatic hit of the normal P53, the absence of both alleles of this tumor suppressor results in pathology
302
"Li-Fraumeni Syndrome is also known as ""SBLA"" Syndrome, which stands for:
"
S - {{c1::Sarcoma}}
B - {{c2::Breast Cancer}}
L - {{c3::Leukemia}}
A - {{c4::Adrenal Gland tumor}}
Loss of the P53 tumor suppressor results in a constellation of tumors due to absence of G1-S checkpoint regulation
303
In regards to wrinkles of aging, there is {{c1::decreased}} synthesis of collagen fibrils and {{c2::increased}} crosslinking of collagen
"
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In contrast to FA2018, UWORLD says there is increased cross linking of collagen
- in aging, the atrophic dermis and increased collagen cross linking + dessication of stratum corneum produce the characteristic wrinkling of photoaged skin
304
A direct ELISA tests for a(n) {{c1::antigen}}, whereas the indirect ELISA tests for a(n) {{c2::antibody against an antigen}}
The antibodies for an indirect ELISA are easier to acquire
305
Patients with ataxia-telangiectasia have vitiligo, granulomas, and a high recurrence of {{c1::sinopulmonary}} infections
recurrent sinopulmonary infections can lead to bronchiectasis; due to being IgA, IgG, and IgE deficient
306
Anthracyclines (-rubicin) bind {{c1::topoisomerase II}} to cause cleavage of DNA
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in addition to binding Fe -> free radical formation
307
Depurination results in the loss of {{c1::purine}} bases
occurs thousands of times per day- sugar phosphate stays in the backbone
