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Evan's Step 1 Prep Material > Molecular EC > Flashcards

Flashcards in Molecular EC Deck (110):
1

Which is transcriptionally active: heterochromatin or euchromatin?

Euchromatin is active

HeteroChromatin is Highly Condenced

2

What do DNA methylation and acetylation do?

Methylation makes DNA Mute (inactive)
Acetylation makes DNA Active

3

What amino acids are required for purine synthesis?

GAG

Glycine, Aspartate, Glutamine

4

What does ribonucleotide reductase do?

reduces nucleotides to deoxy forms

5

What cofactors are required for ribonucleotide reductase action?

thioredoxin and NADPH

*oxidized thioredoxin reduced/recycled by tioredoxin reductase

6

What is the rate limiting step of purine synthesis?

PRPP synthetase

*converts Ribose-5-P to PRPP

7

What ensures balance is maintained in purine synthesis? (2 things)

Cross regulation (GMP requires ATP and vice versa)

Each pathway has end-product inhibition

8

What is the rate-limiting step of pyrimidine synthesis?

CPS-II (formation of carbamoyl phosphate from CO2, glutamine and ATP)

9

What nucleotides is IMP a precursor to?

AMP and GMP

10

What nucleotides are UMP a precursor to?

CTP and TMP

11

What converts dUMP to dTMP?

Thymidylate synthase

12

What causes Orotic aciduria?

How does it present?

What is the treatment?

Defect in UMP synthase (converts orotic acid to UMP)

Presents as megaloblastic anemia UNRESPONSIVE to B12 or folate

Treat with lifetime uridine supplementation

13

What is the sequence from AMP to Uric acid?

AMP-->Adenosine-->Inosine-->Hypoxanthine-->Xanthine--> Uric acid

14

What is the sequence from GMP to Uric acid?

GMP-->Guanine-->Xanthine-->Uric acid

15

What is SCID?

What is its mechanism?

Severe Combined Immunodeficiency Disease

Adenosine deaminase deficiency (inability to convert adenosine to inosine)
*ATP/GTP imbalance inhibits ribonucleotide reductase
*prevents DNA synthesis
*decreased lymphocytes count

16

What is Lesch-Nyhan syndrome?

What is its mechanism?

What are the findings?

Absence of HGPRT (& thus purine salvage)
"He's Got Purine Recovery Troubles"

Results in excess uric acid production

Retardation
Self-mutilation
Aggression
Hyperurecemia/gout
Choreoathetosis

17

What is a silent point DNA mutation?

a mutation that codes for the same amino acid

often a change in the 3rd a.a. (tRNA wobble)

18

What is a missense mutation?

Wrong amino acid but similar chemical structure

19

What is a Nonsense mutation?

Change resulting in easly STOP codon

"STOP the NONSENSE"

20

What is a frameshift mutation?

Misreading all nucleotides downstream

21

Where are the p53 and RB genes located?

p53 is on chromosome 17

RB is on chromosome 13

22

Describe Mismatch Repair

Mismatch repair enzymes recognize mismatched nucleotides

GATC endonuclease makes incision in daughter strand
Removed and gap filled

23

Mutations in mismatch repair enzymes gives rise to what disease?

HNPCC (hereditary nonpolyposal colorectal cancer)

24

Describe base excision repair

Cytosine is spontaneously deaminated to uracil

Uracil DNA glycosylase removes Uracil

AP endonucleases cut DNA and nucleotide is replaced

25

Describe nucleotide excision repair

thymidine dimmers caused by UV light are removed by excision endonucleases

26

What is Xeroderma pigmentosum

Caused by a mutation in excision endonucleases responsible for repairing thymidine dimers

27

Describe direct DNA repair

Alkylation agents (temozolide) cause methylation of Guanine.

MGMT repairs (permanently inactivated and can be depleted)

28

What is nonhomologous end joining?

Repair of double stranded DNA breaks

Caused by iodinizing radiation or free radical oxidation

Mutated in ataxia telangiectasia

29

What phase of the cell cycle to 5-FU and Methotrexate act?

What is the mechanism?

S-phase specific

Inhibit dTMP synthesis to block DNA replication
(5-FU inhibits thymidylate synthase)
(Methotrexate inhibits DHF reductase)

30

In what part of the cell cycle do Bleomycin and Etoposide act?

By what mechanism?

S and G2 phases

Inhibit topoisomerase II (preventing strand sepparation)

31

What is the mechanism of Cyclophosphamide and Nitosoureas?

Alkylating agents that lead to copying errors and expression of abnormal proteins

32

What is the mechanism of Doxorubicin and Actinomycin D?

Intercalated into DNA rand block DNA/RNA polymerases

33

What phase of the cell cycle do vinca alkaloids (vincristine and paclitaxel) work?

What are their mechanisms?

M-phase specific

Vincristine inhibits mitotic spindle formation

Paclitaxel inhibits mitotic spindle breakdown

34

BCL2 proto oncogene function and associated tumors

Inhibits apoptosis

Mutated in follicular B cell lymphoma

35

ERBB2 proto oncogene function and associated tumors

Binds epidermal growth factor

Breast
Ovarian
Stomach

36

MYC proto oncogene function and associated tumors

Activates transcription

Burkitt's Lymphoma
Neuroblastoma

37

RAS proto oncogene function and associated tumors

G protein that transducers growth factor signals

Bladder
Lung
Colon
Pancreas

38

APC tumor suppressor gene function and associated tumors

Inhibits MYC expression

FAP (familial Adenomatous Polyposis)
Colorectal cancer

39

BRCA1 and BRCA2 tumor suppressor gene function and associated tumors

DNA repair

BRCA1
Breast
Ovary
Colon
Prostate

BRCA2
Male and female breast

40

NF1 and NF2 tumor suppressor gene function and associated tumors

Control intra cellular signaling

Neurofibromatosis: optic nerve gliomas, meningioma, acoustic neuroma, pheochromocytoma

41

TP53 tumor suppressor gene function and associated tumors

Mediates G1 arrest and apoptosis

Li-Fraumeni
Breast
Brain
Leukemia
Sarcoma

42

RB1 tumor suppressor gene function and associated tumors

Mediates G1 arrest

Retinoblastoma
Osteosarcoma
Breast cancer

43

WT1 tumor suppressor gene function and associated tumors

Represses transcription in developing kidney

Wilm's tumor

44

Ataxia telangiectasia

Defective DNA repair (double stranded breaks)

Lymphoma

Cerebellar ataxia; dilation of blood vessels in skin and eyes
Immunodeficiency (B and T cells)

45

Bloom's syndrome

Defective DNA repair

Carcinomas, Leukemias, Lymphoma

Facial telangiectasia
Growth retardation
Immunodeficiency

46

Fanconi's anemia

DNA repair defect

Leukemia

Aplastic anemia
Pancytopenia
Congenital abnormalities

47

HNPCC (hereditary nonpolyposis colorectal cancer)

Defective DNA repair (mismatch repair)

Colon, ovary

Tumors before 40

48

Xeroderma pigmentosum

Defective DNA repair (nucleotide excision repair of thymidine dimers)

BCC, SCC, malignant melanoma

Severe skin lesions

49

What is a pseudogene?

Produced by a retrovirus DNA from mRNA

Cannot be expressed (lack promoter and introns)

50

What is a Transposon (jumping gene)?

DNA sequences that insert themselves into different areas of the genome

51

What is a Retrotransposon?

What are examples of genetic diseases caused by Retrotransposons?

Jumping genes that use reverse transcriptase

Can prevent the expression of normal proteins

ei. Hemophilia and Duchenne Muscular Dystrophy

52

What are some drugs that inhibit the G2 phase of the cell cycle?

Etoposide and Bleomycin

inhibit the synthesis of tubulin

53

What are some drugs that inhibit the S phase of the cell cycle?

5-FU and Methotrexate

Inhibit DNA synthesis

54

What are some drugs that inhibit the M phase of the cell cycle?

Colchicine
Paclitaxel
Vinca alkaloids

55

What are CDKs and Cyclins?

CDKs phosphorylate proteins and activate them to promote cell cycle progression

Cyclins bind CDKs and activate them

56

What are p53 and RB?

p53 inhibits G1 to S progression

UN-phosphorylated RB also inhibits G1 to S progression

57

What is DNA Gyrase (topoisomerase II)?

Relaxes NEGATIVE supercoils in DNA replication

58

What is DNA Helicase?

Separates DNA strands

59

What are Single Stranded Binding Proteins?

Prevent strand from re-annealing

60

What is DNA primase?

Makes RNA primer

(DNA polymerase III can initiate from)

61

What is DNA polymerase III?

Elongates leading strand

Exonuclease activity "proofreads"

62

What is DNA ligase?

Seals Okazaki fragments

63

What is telomerase?

Adds DNA to 3' end to maintain chromosome length

*somatic cells do not have telomerase-aging*

64

Types of RNA and polymerases used to synthesize

rRNA (rampant) >> RNA polymerase I
mRNA (massive) >> RNA polymerase II
*inhibited by alpha-amanitin
tRNA (tiny) >> RNA polymerase III

65

What antibiotic inhibits prokaryotic RNA polymerase?

Rifampin

66

What are 3 common sequences in the eukaryotic promoter?

TATA (binds TBP)
CAAT (binds NF1)
CG (binds SP1)

67

hnRNA

primary mRNA transcript containing coding and noncoding sequences
(before introns are removed via splicing)

68

What is the purpose of the cap and tail of the mRNA?

7-methylguanosine CAP orients mRNA on the ribosome

Poly(A) tail increases the half life

69

snRNPs

aggregate at introns forming spliceosomes

SLE - autoantibodies against snRNPs

70

lac operon: Low lactose, low glucose

No transcription

Repressors inhibit expression

71

lac operon: High lactose, low glucose

Transcription

Allolactose inducer
No glucose --> cAMP elevated --> CAP-cAMP complex stimulates transcription

72

lac operon: High lactose, High glucose

No transcription

Allolactose inducer
Glucose-->cAMP low--> no transcription stimulation

*allows glucose to be used up first*

73

Describe drugs resistance in cancer cells due to amplication

The gene for dihydro folate reductase can be increased to levels 3000 times the lethal dose of methotrexate in normal cells.

74

Name two examples of alternative splicing

Fibronectin : extracellular matrix, cell surface, and soluble all from same mRNA
*Removal of carboxy-terminal converts from membrane to soluble protein

IgG heavy chain in B cells

75

mRNA editing of apolipoprotein B

In the GUT: ApoB-48 do not bind LDLR, encoded not to include binding domain

In the LIVER: Apo-100 has LDLR binding domain

76

What are some examples of autosomal dominant diseases?

Familial hypercholesterolemia,
Marfan's,
Osteogenesis imperfecta,
Huntington's
von Williebrand's
Hereditary spherocytosis
Adult poly cystic kidney disease
Neurofibromatosis

77

What are some examples of autosomal recessive diseases?

Inborn errors of metabolism
Sickle cell
Cystic fibrosis
Adrenogenital syndrome
Wilson's disease

78

What are some examples of X lined diseases?

Duchenne's muscular dystrophy
Fabry's disease
Hemophilia A and B
Hunter's syndrome
Lesch-Nyhan syndrome
G6PD deficiency

79

What antibiotics work on the 30S subunit?

Tetracyclins: Bind 30S and block incoming aminoacyl tRNA

Aminoglycosides: Inhibit 30S subunit

Streptomycin: Inhibit 30S subunit

80

What antibiotics work on the 50S subunit?

Chloramphenicol:Inhibits peptidyltransferase activity of 50S

Erythromycin: Inhibits 50S translocation along mRNA

Clindamycin: Inhibits 50S translocation along mRNA

81

What are some antibiotics that work on eukaryotic 60S subunit?

Shiga toxin
Shiga-like toxin (EHEC)
Ricin

~All cleave 28S of 60S subunit which prevents binding of aminoacyl tRNA

82

How does diptheria toxin inhibit protein synthesis?

Inhibits EF-2 (elongation factor 2), inhibiting ribosome translocation

83

What antibiotic targets eukaryotic peptidyl transferase?

Cyclohexamide: fungicidal and rat repellant

84

Describe polypeptide translocation to the RER

Ribosome attaches to ER membrane via SRP

Translocon: directs into ER lumen

Amino end enters first, signal sequence cleaved

Msy be glycosylated in lumen

85

I-Cell disease

Cannot form mannose-6-phosphate on enzymes targeted for lysosomes
~deficient in phosphotransferase needed to add M6P

Enzymes produced normally, but secreted into blood instead of lysosome

*presents with coarse facial features, clouded corneas, restricted joint movement.

86

Ubiquitin

Tags proteins to be degraded in proteosome

87

Vesicular trafficking proteins

COP1: golgi>golgi (retrograde)
golgi>ER
COPII: golgi>golgi (anterograde)
ER>golgi
Clathrin:transGolgi>lysosomes
plasma membrane>endosomes

88

Molecular motor proteins

Dyenein: Retrograde microtubule (+>-)

Kinesin: Anterograde microtubule (->+)

89

Chediak-Higashi syndrome

Pyogenic infections
Partial albinism
Peripheral neuropathy

Mutation in lysosome trafficking regulatory gene (LYST)

90

Drugs that act on microtubules

Mebendazole/thiabendazole (antihelminthic)
Griseofulvin (antifungal)
Vincristine/vinblastine (anti-cancer)
Paclitaxel (anti breast cancer)
Colchicine (anti-gout)

91

Kartagener's syndrome

immotile cilia
Dyenein arm deficiency

Infertility
Bronchiectasis
Recurrent sinusitis
Associated with siatus inversus

92

Drugs that inhibit Na/K pump

Ouabain: inhibits binding to K site

Cardiac glycosides (digoxin/digitoxin)
directly inhibit ATPase
Leads to decreased Na/Ca exchange
Increased intracellular Ca and contractility

93

Collagen types

Type I: Bone, Skin, Tendon
Type II:Cartilage
Type III: Reticulin
Type IV: Basement membrane

"Be (So Totally) Cool, Read Books"

94

Type I collagen

Bone
Skin
Tendon
Dentin
Fascia
Cornea
Late wound repair

Defective in osteogenesis imperfecta

95

Type II collagen

Cartilage
Vitreous body
Nucleus pulposus

96

Type III collagen

Reticulin (skin, blood vessels, uterus, fetus, granulation tissue)

Defective in Ehlers-Danlos

97

Type IV collagen

Basement membrane

Defective in Alport syndrome

98

Collagen synthesis

1) Synthesis (RER): Gly-X-Y
2) Hydroxylation (ER): of proline and lysine (required vit. C)
3) Glocosylation (ER): of hydroxylysine, hydrogen and disulfide bond formation
4) Exocytosis into extracellular space
5) Cleavage: of terminal regions into insoluble tropocollagen
6) Cross-link: Forming fibrils

99

Multiple fractures, blue sclerae, hearing loss, dental imperfections

Osteogenesis imperfecta

100

Congenital nephritis, deafness, and ocular disturbances

Alport syndrome (type IV collagen)

101

Prader-Willi syndrome

Paternal allele not expressed

Retardation
Hyperphagia/obesity
Hypogonadism
Hypotonia

102

Angelman syndrome

Maternal allele not expressed

Retardation
Seizures
Ataxia
Inappropriate laughter

103

Trinucleotide repeat expansion diseases

Fragile X: (CGG)
Friedreich's ataxia: (GAA)
Huntington's: (CAG)
Myotonic dystrophy: (CTG)

"X-Girlfriends First-Aid Helped-Ace My-Test"

104

Autosomal trisomies

21-Downsyndrome
18-Edwards (rocker-bottom feet, small jaw)
13-Patau's (rocket-bottom feet, cleft palate, microophthalmia/cephaly, polydactyly)

"Drink at 21, Election at 18, Puberty at 13"

105

Robertsonian translocation

Nonreciprocal chromosomal translocations
13,14,15,21,22
Long arms fuse @ centromere and short arms are lost

106

Cri-du-chat syndrome

Microdeletion of short arm of chr 5

microcephaly, retardation, high-pitched crying/mewing, epicanthal folds, cardiac VSD

107

Williams syndrome

Microdeletion of long arm of chr. 7

Elfin facies
Intellectual disability
Hypercalcemia (increased vit. D def)
Well-developed verbal skills/extreme friendliness
Cardiovascular problems

108

22q11 deletion syndromes

Aberrant devo of 3rd and 4th branchial pouches

Cleft palate
Abnormal facies
Thymic aplasia
Cardiac defects
Hypocalcemia

"CATCH-22"

109

DiGeorge syndrome

22q11 deletion

Thymus
Parathyroid
Cardiac defects

110

Velocardiofacial syndrome

22q11 deletion

Palate
Facial
Cardiac defects

Decks in Evan's Step 1 Prep Material Class (72):