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Cancer Biology > Test I > Flashcards

Test I Flashcards

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1
Q

Albinism

A

Defective melanin synthesis - lack of pigmentation, white hair, pink skin

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2
Q

Homocystinuria

A

Defective methionine degradation - faulty bone development, mental retardation

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3
Q

Branched-chain ketoaciduria (Maple syrup urine disease)

A

Defective isoleucine, leucine, valine degradation - vomiting, convulsions, mental retardation, early death

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4
Q

PKU (phenylketonuria)

A

Defective conversion of phenylalanine to tyrosine - vomiting, mental retardation, seizures

Aspartame ingestion restricted

Typical (defective phenylalanine hydroxylase) and Atypical (defective dihydrobiopterin reductase) - atypical treated by Sapropterin (Kuvan)

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5
Q

Tyrosine-derived biomolecules

A

thyroid hormones, catecholamines, melanin, fumarate+acetoacetate

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6
Q

Sapropterin (Kuvan)

A

treats atypical PKU (caused by dihydrobiopterin reductase deficiency) - tetrahydrobiopterin analog, pushes phenylalanine hydroxylase reaction forward to convert more phenylalanine to tyrosine

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7
Q

Translation inhibitors of prok & euk, prok only, euk only

A

p+e: puromycin

p: streptomycin, tetracycline and chloro-/erythro-mycin
e: cycloheximide and diptheria toxin

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8
Q

Tetracycline

A

translation inhibitor of prokaryotes but not eukaryotes, blocks binding of aa-tRNA to A site of ribosome

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9
Q

Streptomycin

A

translation inhibitor of prokaryotes but not eukaryotes, prevents translation initiation complex from forming causes miscoding

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10
Q

Cycloheximide

A

translation inhibitor of eukaryotes by not prokaryotes, blocks translocation on ribosome

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11
Q

Puromycin

A

translation inhibitor of prokaryotes and eukaryotes, adds to polypeptide and can’t be extended, causing premature ejaculation of polypeptide fro ribosome

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12
Q

Diptheria toxin

A

kills cells - blocks eukaryotic translation, blocks translocation on ribosome by adding ADP-ribosyl to EF2, causes cell death

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13
Q

Polio virus mechanism

A

causes proteolysis of cap binding protein (eIF4E) for host mRNA, allowing its own mRNA to be translated by host machinery

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14
Q

Diseases from premature termination of translation

A

CF (CFTR - Cystic Fibrosis Transport Regulator), beta-thalassemia (beta globin), DMD (Duchene Muscular Dystrophy - dystrophin), Hurler Syndrome

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15
Q

miRNAs

A

21-25 nts long, affect expression of 60% of protein encoding genes, often bind 3’UTR of mRNAs (though can affect RNAs involved at any point), usually act by degrading mRNA - though some cases of activating translation have been reported

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16
Q

CF

A

most common cause: deletion of F508 in CFTR - gets marked for degradation by proteosome via ERAD even though protein is often still functional -> possible treatment: inhibit Aha1 to prveent ERAD & save some CFTR

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17
Q

vCJD

A

variant Creutzfeld-Jakob Disease - psychiatric problems, behavioral changes, painful sensations - prion disease, bovine spongiform encephalopathy (BSE / madcow)-like prions - alpha to beta reversible interconversion normally, and in disease a beta crystal induces other alpha helices to convert to beta sheets & beta aggregates form

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18
Q

hemophilia A

A

congenital bleeding disorder of varying severity - deficient or defective Factor VIII in clotting

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19
Q

ALS - Amyotrophic Lateral Sclerosis (Lou Gherig’s Disease)

A

muscle weakness, spasms, difficulty speaking, eventually death - mutated SOD1 (Cu/Zn superoxide dismutase), functional dimers don’t form, leading to aggregation

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20
Q

M2-PK / Warburg effect

A

M2PK converted in cancers to two dimers instead of normal tetramer, preventing PEP->pyruvate, allowing redirection to pentose phosphate pathway

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21
Q

Prader-Willi Syndrome

A

intellectual impairment, behavior/eating disorders, delayed/incomplete puberty - Maternal imprinting, deletion on portion of paternal chromosome 15

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22
Q

Angelman Syndrome

A

excitable, ataxia, hyperactive, delayed development, mentally retarded, speech impairment, microcephaly - Paternal imprinting, deletion on portion of maternal chromosome 15

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23
Q

I-cell disease

A

coarse facial features, skeletal abnormalities, mentally retarded - cannot mark proteins w/ M6P for lysosomal degredation due to defect in GlcNAc phosphotransferase

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24
Q

Kennedy’s Disease (Spinal and Bulbar Muscular Atrophy)

A

twitching, infertility, throat problems, muscle weakness - aggregation of protein w/ polyQ expansion androgen receptor (AR) in cytoplasm since nuclear importin (RAN) can’t bind -> no transcription of genes responsive to androgen hormones, X-linked neurodegenerative disorder

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25
Q

Penetrance and Frequency (High and Low) Examples:

A

HP/LF: HNPCC(colon cancer), BRCA 1 & 2 (breast cancer), MODY 1,2,3 (diabetes), α-synuclein (parkinsons disease)

LP/HF: APC I1307K (cancer), ApoE (alzheimers), Factor V Leiden(thromboembolic events/stroke), CCR5 (HIV)

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26
Q

Alcohol flush reaction

A

red flush, caused by accumulation of acetaldehyde due to point mutation in aldehyde dehydrogenase (increased Km, slower binding)

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27
Q

HGPS (Hutchinson-Guillford progeria syndrome)

A

rapid aging, stunted growth, full body hair loss - due to extra splicing inclusion (or incomplete lipidation) in lamin A

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28
Q

ALL (Acute Lymphoblastic Leukemia )

A

cancer in precursor of T/B cells, 9q/22q philadelphia chromosome rearrangement, Abl kinase gene overexpressed - treated by Imatinib (Gleevec) which inhibits Abl kinase, only long term treatment a bone marrow transplant

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29
Q

Holoprosencephaly

A

developmental abnormalities (e.g., cyclopsia), due to mutation in SHH pathway, can be caused by lack of proper cholesterol synthesis/modification (precursor to SHH)

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30
Q

Hurler Syndrome

A

skeletal abnormalities, mental retardation, heart disease - nonsense mutation in alpha iduronase, lysosomal storage disease, aggregation of GAGs/mucopolysaccharides

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31
Q

Beta Thalassemia

A

fatigue, SOB, slow growth - nonsense mutation of beta globin

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32
Q

Duchenne Muscular Dystrophy (DMD)

A

loss of muscle - nonsense mutation in dystrophin

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33
Q

Sickle cell anemia

A

fatigue, pain, frequent infections - glu-val mutation in beta chains, proteins aggregate

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34
Q

Bcl-xl

A

allows cancer cells to avoid apoptosis - changed 5’ splice site, larger protein, prevents apoptosis

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35
Q

BRCA1

A

breast and ovarian cancer - exon skipped due to mutation in ESE (exon splicing enhancer) binding site

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36
Q

Spinal Muscular Atrophy

A

neurodegeneration - introduction of hnRNP prevents inclusion of an exon, shortened protein is dysfunctional

37
Q

46BR Patient

A

hypersensitivity to DNA-damaging agents, genome instability - defective DNA ligase I

38
Q

Fanconi anemia Groups A-G

A

congenital abnormalities, leukemia, genome instability - impaired DNA interstrand crosslink repair

39
Q

Bloom Syndrome

A

stunted growth, various cancers, genome instability - accessory DNA helicase affected

40
Q

Werner Syndrome

A

premature aging, various cancers, genome instability - accessory 3’ exonuclease & DNA helicase affected

41
Q

AT (Ataxia Telangiectasia)

A

leukemia, lymphoma, gamma ray sensitibvity, genome instability - ATM (protein kinase) affected

42
Q

BRCA2

A

breast, ovarian and prostate cancer - homologous repair affected

43
Q

XP (xeroderma pigmentosum) variant

A

UV sensitivity, skin cancer - translesion synthesis by DNA polymerase eta affected

44
Q

XP (xeroderma pigmentosum) groups A-G

A

UV sensitivity, skin cancers, neurological abnormalities - NER (nucleotide excision repair) affected

45
Q

MSH 2,3,6; MLH1; PMS2

A

colon cancer- mismatch repair affected

46
Q

Tay-Sachs

A

mental deterioration starting @ 6 months, blindness, paralysis, death by age 4 - mutation in HEXA gene on chromosome 15, dysfunctional hexosaminidase lysosomal protein, buildup of lipids in brain

47
Q

Zellweger Syndrome

A

death in first decade, dysfunctional peroxisomes

48
Q

Cholera

A

diarrhea, dehydration - causes CFTR to transport lots of Cl- into intestine, Na+ and water follow - treated by isotonic saline and glucose

49
Q

Marfan Syndrome

A

Tall, long limbs, mitral valve prolapse, aortic dissection - due to mutated fibrillin-1 protein

50
Q

Primary Cilia Dyskinesia

A

chronic respiratory problems, otitis, infertility, ectopic pregnancy, hydrocephalus - dysfunction of cilia / flagella

51
Q

EDS (Ehlers-Danlos Syndrome)

A

hyper-flexible skin w/ no tensile strength - due to mutations in collagen types I and III

52
Q

MERRF (Myoclonic Epilepsy w/ Ragged Red Fibers)

A

epilepsy, ataxia, weakness, dementia - mitochondrial disorder, mutation in mitochondrial lysine tRNA prevents ATP production

53
Q

LHON (Leber’s Hereditary Optic Neuropathy)

A

degeneration of retinal ganglion cells, predominantly in young males - mitochondrial disorder

54
Q

Azidothymidine (AZT)

A

deoxythimidine analog, toxic but taken up by HIV 100 times faster - NRTI

55
Q

Methotrexate

A

inhibits DNA synthesis (anti-cancer drug) - dihydrofolate reductase inhibitor, folic acid analog, blocks dTMP synthesis from dUMP - directly inhibits pyrimidine synthesis, indirectly inhibits purine synthesis

56
Q

MG98

A

DNMT1 inhibitor - cancer treatment

57
Q

Decitabine

A

global DNMT inhibitor - cancer treatment

58
Q

Azacitidine

A

global DNMT inhibitor - cancer treatment

59
Q

Rapamycin

A

activates autophagy

60
Q

Aspirin

A

irreversible inhibitor of COX-1 - NSAID

61
Q

Penicillin

A

irreversible inhibitor of bacterial transpeptidase (enzyme that forms crosslinks in bacterial cell wall) - a beta-lactam antibiotic

62
Q

Fluorouracil

A

irreversible “suicide” inhibitor of thimidylate synthase, uracil analog, inhibits thymidine synthesis and thus DNA replication - cancer therapy drug

63
Q

Allopurinol

A

inhibits xanthine oxidase, analog of hypoxanthine, reduces uric acid production - treatment for Gout

64
Q

Dexrazoxone

A

Topo-II inhibitor, prevents it from detaching from dsDNA

65
Q

Camptothecin

A

Topo-I inhibitor, leads to apoptosis

66
Q

Cisplatins

A

covalently binds DNA, intra-/inter-/protein-crosslinks (G-G crosslinks and kinks stall DNA repair), causes apoptosis - cancer treatment

67
Q

Bleomycins

A

ss and ds DNA breaks in presence of O2 and Fe(II)

68
Q

Phenoxazone Ring (e.g. Dactinomycin)

A

inhibits (stalls) DNA transcription, planar rings intercalate, side chains bind minor groove

69
Q

Kartagener’s Syndrom

A

absence of dynein arms - type of PCD (primary ciliary dyskisesia)

70
Q

Young’s Syndrome

A

malformation of radial spikes and dynein arms - type of PCD (primary ciliary dyskinesia)

71
Q

Anthracyclins (e.g., Doxorubicin)

A

block DNA replication - inhibits Topo-II, histone eviction

72
Q

Gentamicin

A

stop codon bypass - inhibits release factor @ stop codon in translation - treats Duchenne Muscular Dystrophy (nonsense mutation in dystrophin gene)

73
Q

Classify these proteases: Chymotrypsin, HIV protease, Thermolysin, Trypsin, Renin, Papain.
[What is the role of the main functional piece of each type of protease?]

A

Serine: Trypsin and Chymotrypsin [Ser = catalytic and covalent]
Cysteine: Papain [Cys = cat. and cov.]
Aspartyl: HIV protease and Renin [Asp = cat. only]
Metallo: Thermolysin [ion = cat. only]

74
Q

HIV protease inhibitors, Statins and Methotrexate are what type of inhibitors?

A

Tight binding

75
Q

5-Fluorouracil, Penicillin & Aspirin are what type of inhibitors?

A

Irreversible

76
Q

The 4 places proteins can go from free ribosomes in cytosol:

A

Nucleus, ER, Mitochondria, Cytosol

77
Q

Alzheimer’s, Parkinson’s, Huntington’s, ALS, CJD, SSA cardiomyopathy, Type II Diabetes can all be caused by:

A

Protein Aggregation

78
Q

CF, Marfan syndrome, Fabry disease, Gaucher’s disease, Retinitis pigmentosa, Cancer can all be caused by:

A

Protein Misfolding (CFTR, Fibrillin-1, alpha galactosidase, beta-glucocerebrosidase, rhodopsin, p53)

79
Q

Mediates entry of proteins from cytosol into mitochondrial matrix

A

TIM/TOM complex (proteins have N-terminal amphipathic helix, + charge on one end, hydrophobic on the other)

80
Q

HGPS, SMA, Cancer (CD44, BRCA1, & Bcl-xl) can all be caused by:

A

mutations producing incorrect splicing (BRCA1->breast & ovarian cancer, Bcl-xl->melanoma & SCLC)

81
Q

where protein glycosylation occurs

A

ER

82
Q

Colchicine, Vinblastine, Vincristine and Nocodazole

A

tubulin polymerization inhibitors

83
Q

Taxole

A

microtubuledepolymerization inhibitor

84
Q

Bortezomib

A

proteasome inhibitor, binds catalytic site of 26S core

85
Q

Chloramphenicol

A

prokaryotic translation inhibitor - binds 50S subunit & blocks peptidyltransferase activity

86
Q

Cindamycin

A

prokaryotic translation inhibitor - binds 50S subunit & blocks translocation

87
Q

Tamiflu

A

neuraminidase inhibitor - prevents influenza virus from infecting other cells

88
Q

SAHA (Vorinostat)

A

HDAT inhibitor - increases transcription of targeted genes

Cancer Biology (2 decks)

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