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Molecules to Medicine > Unit 1 > Flashcards

Unit 1 Flashcards

1
Q

______ is an important precursor in the biosynthesis of Vitamin C, deficiency of which results in _______.

A

hydroxyproline; scurvy

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2
Q

_______ (HDACs) _______ the N-termini of histones, which restores the _______ charge on _______ residues

A

Histone deacetylases; deacetylate; positive; lysine

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3
Q

_______ acetylate _______ of histones, which neutralizes the _______ charge on _______ residues.

A

Histone acetyltransferases (HATS); N-termini; positive; lysine

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4
Q

_______ competitively binds to bcr-abl, a _______, and inhibits its activity.

A

Gleevec; tyrosine kinase

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5
Q

_______ induces eIF2A phosphorylation which inhibits ternary complex formation, thereby preventing initiation and translation globally

A

Interferon

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6
Q

_______ is a blood thinner by inhibiting modification to produce _______

A

Warfarin (coumadin); gamma-carboxyglutamate

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7
Q

_______ upregulates translation by binding to _______, which phosphorylates 4E-BP1, which can no longer bind 4E; 4E binds the Cap

A

Rapamycin; mTOR (mammalian target of Rapamycin)

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8
Q

53BP binds during _____ phase and dissociates during ____ phase or ___ phase.

A

G1; S; G2

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9
Q

Accumulation of purines of low solubility can help describe the symptoms of which two pathologies?

A

Lesch-Nyhan disease, gout

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10
Q

Actinomycin and doxorubicin (Adriamycin) have what biochemical effect?

A

The intercalate with DNA and interfere with DNA function

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11
Q

CDK2-cycE inhibits _______ protein which promotes cell division.

A

retinoblastoma

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12
Q

CDK2-cycE inhibits retinoblastoma protein which _______ cell division.

A

promotes

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13
Q

Chk1 and Chk2 are activated by _______; they then activate DNA repair and _____ cell cycle progression.

A

ATR/ATM; inhibit

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14
Q

Cisplatin

A

This is an alkylating-like compound: it forms covalent adducts and inhibits transcription

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15
Q

Defective Nucleotide Excision Repair mechanisms result in which two pathologies?

A

Cockayne’s Syndrome and Xeroderma Pigmentosum

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16
Q

Define the function of hMLH and hMSH.

A

Enzymes involved in mismatch repair DNA repair mechanism

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17
Q

Define the function of MutS and MutL.

A

Enzymes involved in mismatch repair DNA repair mechanism

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18
Q

Describe the high energy bond types

A

thioester (C-S), phosphoanhydrides, P-N bonds, C-O-P bonds

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19
Q

Dimethylnitrosamine, nitrogen mustard, and dimethylsulfide affects DNA in what way?

A

These are alkylating agents: they form covalent adducts that inhibit transcription

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20
Q

Exome sequencing is useful in diagnosing diseases with ____ patterns of inheritance, such as _______.

A

Mendelian; Miller’s Syndrome

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21
Q

Hepatitis A and C, HIV, and Polio cleave _____ to shut down cap-dependent translation

A

eIF4G

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22
Q

How is the activity of Beta-catenin regulated?

A

GSK3 (with APC and Axin) phosphorylates Beta-catenin and targets it for degradation via ubiquitin-proteasome pathway; Wnt destabilizes the Axin/APC/GSK3 complex to allow beta-catenin to persist

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23
Q

How is the activity of CREB regulated?

A

CREB (cAMP Response Element Binding protein) requires phosphorylation to be activated

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24
Q

How is the activity of NF-AT regulated?

A

NF-AT is phosphorylated which blocks the NLS; Under high calcium conditions, calineurin dephosphorylated NF-AT and permits nuclear entry

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25
Q

How is the activity of Nf-kB regulated?

A

I-kB binds to Nf-kB and blocks the NLS; Phosphorylation of I-kB causes dissociation and permits nuclear entry

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26
Q

How is the activity of p53 regulated?

A

MDM2 binds to p53 and masks its activation domain and targets it for destruction; high levels of p53 activate transcription of MDM2

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27
Q

How is the activity of the glucocorticoid receptor regulated?

A

Hsp90 is bound preventing entry to nucleus; binding of a hormone causes dissociation from Hsp90 and permits nuclear entry

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28
Q

In _______, Ku recognizes the DSB and recruits DNA PK-cs.

A

Non-homologous End Joining (NHEJ)

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29
Q

In multiple myeloma, proteasome activity is _______.

A

high

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30
Q

In Non-homologous End Joining (NHEJ), _______ recognizes the DSB and recruits _______.

A

Ku; DNA PK-cs

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31
Q

Ink4 and Cip/Kip inhibit _______, which _______ cell cycle progression

A

CDKs; inhibits

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32
Q

Interferon induces _______ phosphorylation which inhibits ternary complex formation, thereby preventing initiation and translation globally

A

eIF2A

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33
Q

Interferon induces eIF2A phosphorylation which inhibits ternary complex formation, thereby preventing _______.

A

translation

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34
Q

Monoclonal ab infusion, bapineuzamab, solanezumab, and IVIg are strategies to…

A

Increase Beta-amyloid clearance

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35
Q

Name 3 pathologies associated with mutations of TFIIH.

A

Xeroderma Pigmentosum, Cockayne’s Syndrome, and Trichothiodystrophy

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36
Q

Name 4 compounds that form covalent adducts with DNA to inhibit transcription

A

Dimethylnitrosamin, nitrogen mustard, dimethylsulfide, and cisplatin

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37
Q

Name 4 viruses that shut down cap-dependent translation?

A

Hepatitis A and C, HIV, and Polio

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38
Q

Name the cause of Fragile-X Syndrome and some of the clinical observations.

A

An increase in CGG repeats in the FMR gene; mental retardation, craniofacial defects, and macroorchidisim

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39
Q

Name the DNA-binding region category for the following DNA binding proteins: Androgen receptor, MyoD, Pit1, c-fos

A

Zn finger; Helix-loop-helix; Helix-turn-helix; bZIP

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40
Q

Name the DNA-binding region category for the following DNA binding proteins: c-fos, c-jun

A

Basic Leucine Zipper (bZIP)

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41
Q

Name the DNA-binding region category for the following DNA binding proteins: c-jun, Myf5, Msx

A

bZIP; Helix-loop-helix; helix-turn-helix

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42
Q

Name the DNA-binding region category for the following DNA binding proteins: estrogen receptor, androgen receptor, retinoic acid receptor

A

Zinc Finger

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43
Q

Name the DNA-binding region category for the following DNA binding proteins: Hox family, Pit1, Msx

A

Helix-turn-helix

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44
Q

Name the DNA-binding region category for the following DNA binding proteins: Hox family, retinoic acid receptor, Myogenin

A

Helix-turn-helix; Zn Finger; Helix-loop-helix

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45
Q

Name the DNA-binding region category for the following DNA binding proteins: MyoD, Myogenin, Myf5

A

Helix-loop-Helix

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46
Q

Name the homologs of MutS and MutL.

A

hMSH and hMLH

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47
Q

Name the three enzymes (in order) involved in installing the 5’ cap

A

Triphosphatase; Guanylyltransferase; Guanine 7-methyltransferase

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48
Q

Name two ATP-dependent ATPases.

A

SWI and SNF

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49
Q

Name two classes of proteins that inhibit CDKs

A

Ink4 and Cip/Kip

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50
Q

Name two drugs that interfere with DNA function via intercalation

A

Actinomycin and doxorubicin (adriamycin)

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51
Q

Name two drugs that interfere with DNA function via topoisomerase inhibition.

A

Camptothecin and etoposide

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52
Q

Provide an example for each of the high energy bond types.

A

Acetyl CoA, Phosphoenolpyruvate, ATP, Creatine

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53
Q

Rad 17 senses damaged DNA, which activates the transducers _______, which activate the effectors _______, which inhibit _______.

A

ATR/ATM; p53/p21; CDKs

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54
Q

Rapamycin upregulates _______ by binding to mTOR (mammalian target of Rapamycin), which phosphorylates _______, which can no longer bind _______ –> _______ binds the Cap

A

translation; 4E-BP1; 4E; 4E

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55
Q

T/F Binding of the IRE is required for expression of ferritin.

A

F

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56
Q

T/F Binding of the IRE is required for expression of the transferrin receptor.

A

T

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57
Q

T/F HATs promote transcription.

A

T

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58
Q

T/F HDACs promote transcription.

A

F

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59
Q

What Alzheimer’s treatment method seeks to increase glucose uptake and synaptogenesis?

A

Intranasal Insulin

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60
Q

What are the biochemical effects of etoposide and camptothecin?

A

They interfere with topoisomerase activity which results in irreparable breaks in DNA

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61
Q

What are the homologs of Hsp70/Hsp40?

A

DnaK/DnaJ

62
Q

What are the names of the eukaryotic polymerases?

A

Polymerase delta (lagging) and Polymerase epsilon (leading)

63
Q

What causes Lesch-Nyhan disease?

A

Accumulation of purines of low solubility

64
Q

What chaperone uses ATP to fold proteins correctly?

A

GroES/GroEL

65
Q

What drug can be used to inhibit HIV protease?

A

Crixivan

66
Q

What drug can be used to reduce blood pressure?

A

Captopril

67
Q

What drug is involved in inhibition of protein methylation and acetylation?

A

Verinostat

68
Q

What drug is used to treat Chronic Myelogenous Leukemia (CML)?

A

Gleevec

69
Q

What drug mimics the structure of an aminoacyl-tRNA to inhibit translation?

A

Puromycin

70
Q

What drug prevents the binding of estrogen to the estrogen receptor?

A

Tamoxifen

71
Q

What drug prevents transcription by blocking the RNA exit site?

A

Rifampicin

72
Q

What enzyme is responsible for installation of the Poly A tail?

A

Polyadenylate Polymerase

73
Q

What is an X-linked disorder that affects blood clotting

A

Hemophilia B Leyden

74
Q

What is targetted for degradation by the Axin/APC/GSK3 complex?

A

Beta-catenin

75
Q

What is the 3’ splice site consensus sequence?

A

AG

76
Q

What is the 5’ splice site consensus sequence?

A

GU

77
Q

What is the biochemical cause of CDG-1?

A

Defect in N-linked glycosylatio of Asn

78
Q

What is the biochemical cause of craniosynosis?

A

A proline to histidine mutation in the MSX2 gene that leads to activation of suture closure genes

79
Q

What is the biochemical cause of Hemophilia B Leyden?

A

Mutation in the Factor IX gene that interferes with the binding of transcriptional activators

80
Q

What is the biochemical cause of Rubinstein-Taybi Syndrome?

A

Haploinsuffiency of CREB Binding Protein (CBP)

81
Q

What is the biochemical consequence of haploinsufficiency of CBP?

A

CBP is an activator for many transcription processes and has HAT activity

82
Q

What is the biochemical effect of a mutation in a binding domain of the androgen receptor?

A

Decreased response to androgens/Androgen Insensitivity Syndrome

83
Q

What is the biochemical effect of puromycin?

A

It mimics aminoacyl-tRNA, (1) binds the active site of the ribosome, (2) is transferred to the growing polypeptide chain, and (3) prevents completion of translation

84
Q

What is the biochemical effect of rapamycin?

A

Rapamycin upregulates translation by binding to mTOR (mammalian target of Rapamycin), which phosphorylates 4E-BP1, which can no longer bind 4E –> 4E binds the Cap

85
Q

What is the biochemical function of BRCA2?

A

Sense double strand breaks in damaged DNA

86
Q

What is the biochemical function of ferritin?

A

Sequesters excess iron

87
Q

What is the biochemical function of Hsp70/Hsp40?

A

Prevent protein aggregation by binding to hydrophobic residues and transporting unfolded proteins across membranes

88
Q

What is the biochemical function of Id?

A

Id heterodimerizes with bHLH domains and prevents binding of DNA binding proteins

89
Q

What is the biochemical function of IRE-BPs?

A

When Fe is high, they bind to Fe; when Fe is low, they bind to IRE

90
Q

What is the biochemical function of IRE?

A

IRE (Iron Response Element) is a region on RNA that may be bound by IRE-BPs and then influence the expression of ferritin and transferrin

91
Q

What is the biochemical function of the transferrin receptor?

A

Transports transferrin/Iron into the cell

92
Q

What is the biochemical significance of ApoE4?

A

ApoE4 is associated with an increase in Alzheimer’s Disease by increasing amyloid deposition

93
Q

What is the biochemical target of aminoglycosidases (Ex. Stretpomycin) and tetracyclines?

A

The ribosome

94
Q

What is the biochemical target of macrolides (ex. erythromycin) and chloramphenicol?

A

The ribosome

95
Q

What is the cause of Beta thalassemia?

A

Mutation in promoter region of Beta-gobin gene that results in decreased expression

96
Q

What is the cause of Cockayne’s Syndrome?

A

Defect in NER

97
Q

What is the cause of Gamma-Delta-Beta thalassemia?

A

Deletion of Locus Control Region (LCR), which is required for transcription of genes in the cluster

98
Q

What is the cause of thalassemia?

A

Inherited anemia due to deficiency of Beta-globin in erythroid cells

99
Q

What is the cause of Xeroderma Pigmentosum?

A

Defect in NER

100
Q

What is the clinical consequence of chromosomal translocations that form functional fusion proteins?

A

Hematopoietic malgnancy (leukemia) due to altered activity of transcription regulators

101
Q

What is the consequence of a defect in N-linked glycosylation of Asn?

A

Congenital Disorder of Glycosylation 1 (CDG-1)

102
Q

What is the consequence of a mutation in the DNA-binding or ligand-binding domains of the androgen receptor?

A

Androgen Insensitivity Syndrome

103
Q

What is the consequence of a mutation in the microphthalmia associated transcription factor (MITF)?

A

Waardenburg Syndrome Type II

104
Q

What is the consequence of a mutation in the SMN1 gene?

A

Exclusion of exon 7 and Spinal Muscular Atrophy

105
Q

What is the consequence of a proline to histine mutation in MSX2?

A

Craniosynosis

106
Q

What is the function of ASO oligonucleotide?

A

Treatment of Spinal Muscular Atrophy by promoting inclusion of exon 7

107
Q

What is the function of DNA dependent ATPases (Ex. SWI/SNF)?

A

Disrupt histone octamers and DNA interactions

108
Q

What is the function of DNA glycosylase in DNA Repair?

A

DNA glycosylase cleaves the N-glycosidic bond to result in an apurinic site in Base Excision Repair

109
Q

What is the function of gyrase?

A

Topoisomerase in bacteria that relaxes supercoils in DNA

110
Q

What is the function of polymerase delta?

A

Lagging Strand analog of DNA polymerase III

111
Q

What is the function of polymerase epsilon?

A

Leading Strand analog of DNA polymerase III

112
Q

What is the function of TFIID?

A

Contains TBP (TATA Binding Protein) and directs assembly of the pre-initiation complex at the promoter

113
Q

What is the function of TFIIH?

A

Contains XPB helicase (opens DNA at the promoter region) and CDK7 which phosphorylates the CTD during clearance

114
Q

What is the function of the Beta subunit (prokaryotes) and PCNA (eukaryotes)?

A

These act as a sliding clamp that increases the processivity of DNA polymerase III

115
Q

What is the mode of action of alpha-amanitin?

A

Competitive inhibitor of RNA polymerase by binding to the bridge helix?

116
Q

What is the mode of action of Bortezomib?

A

Inhibits the proteasome and decreases rates of ubiquitination

117
Q

What is the mode of action of captopril?

A

Inhibits ACE (angiotensin converting enzyme)

118
Q

What is the mode of action of HDAC inhibitors?

A

Inhibit protein methylation/acetylation, which are important modifications in histone modifying proteins

119
Q

What is the mode of action of Rifampicin?

A

Blocks RNA exit site to inhibit transcription?

120
Q

What is the mode of action of Tamoxifen?

A

Binds to the estrogen receptor, preventing binding of estrogen, which inhibits recruitment of HATs

121
Q

What is the molecular basis of Spinal Muscular Atrophy?

A

Mutation of SMN1 which results in exclusion of exon 7

122
Q

What is the poly A site consensus sequence?

A

AAUAAA

123
Q

What is the role of MDM2 in regulation?

A

MDM2 binds to p53 and masks its activation domain and targets it for destruction; high levels of p53 activate transcription of MDM2

124
Q

What is the role of the Shine-Dalgarno sequence?

A

In translation, mRNA binds the 30S subunit using this sequence

125
Q

What is the role of Wnt signaling in Beta-catenin regulation?

A

Wnt signaling destabilizes the APC/Axin/GSK3 complex that targets Beta-catenin for degradation

126
Q

What is the sliding clamp referred to as in prokaryotes? Eukaryotes?

A

Beta subunit; PCNA

127
Q

What is the target of quniolones in the inhibition of DNA replication?

A

Quinolones inhibit topoisomerases

128
Q

What is transcribed by RNA polymerase I?

A

rRNA

129
Q

What is transcribed by RNA polymerase II?

A

mRNA, miRNA, siMRNA, lncRNA

130
Q

What is transcribed by RNA polymerase III?

A

tRNA, specialized RNA

131
Q

What pathology is characterized by a defect in the FMR1 gene with an increase in CGG repeats?

A

Fragile X Syndrome

132
Q

What pathology is characterized by an insertion of proline into an alpha helix structure?

A

Thalassemia

133
Q

What pathology is characterized by deafness and pigmentation defects of the eyes, hair, and skin?

A

Waardenburg Syndrome Type II

134
Q

What pathology is characterized by developmental defects, neurological abnormality, and brittle hair?

A

Trichothiodystrophy

135
Q

What pathology is characterized by feminization or undermascularization of external genitalia at birth, abnormal secondary sexual characteristic development at puberty, and infertility?

A

Androgen Insensitivity Syndrome

136
Q

What pathology is characterized by multisystem disorder: growth retardation, mental retardation, craniofacial defects, and abnormally broad thumbs and big toes?

A

Rubinstein-Taybi Syndrome

137
Q

What pathology is characterized by premature fusion of sutures in the skull that limits the brain’s ability to grow and craniofacial abnormalities?

A

Craniosynosis

138
Q

What pathology is characterized by sun hypersensitivity, premature aging, impaired development, impaired development, and neurological degeneration?

A

Cockayne’s Syndrome

139
Q

What pathology is characterized by sun hypersensitivity, skin neoplasms, and neurological degeneration (later)?

A

Xeroderma Pigmentosum

140
Q

What protein is involved in the balance of NEHJ and HR DSB repair?

A

53BP

141
Q

What toxin comptetitively binds to RNA polymerase to prevent transcription?

A

alpha-amanitin

142
Q

What types of RNA comprise the category of regulatory RNAs?

A

miRNA, siRNA, lncRNA

143
Q

What types of RNA comprise the category of structural RNAs?

A

tRNA, snRNA, snoRNA, rRNA

144
Q

What X-linked pathology is characterized by mental retardation, craniofacial defects, and macroorchidisim?

A

Fragile-X Syndrome

145
Q

When there is a vitamin K deficiency, modification to synthesize _______ cannot occur, which results in blood thinning

A

gamma-carboxyglutamate

146
Q

Which 3 trans acting factors are controlled by nuclear entry?

A

NF-AT, Nf-kB, and glucocorticoid receptor

147
Q

Which DNA repair mechanism uses DNA glycosylase?

A

Base Excision Repair

148
Q

Which transcription factor contains CDK7? What is the function of CDK7?

A

TFIIH; phosphorylates CTD during clearance

149
Q

Which transcription factor contains TBP?

A

TFIID

150
Q

Which transcription factor contains XPB helicase?

A

TFIIH

151
Q

Which two trans acting factors are regulated by their intracellular concentration?

A

p53 and Beta catenin

Molecules to Medicine (5 decks)

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