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Flashcards in Bicohem Deck (194):
1

Histones are rich in what two amino acids making it positively charged?

lysine and arginine

2

What phase do DNA and histone synthesis occur in?

S phase

3

Inactive DNA and histone morphology?

Heterochromatin. Deacetylated and methylated histones allows for tight association and transcriptionally inactive)

4

Active DNA and histone morphology?

Euchromatin. Acetylated and non-methylated histones allow for loose association and transcriptionally active)

5

What is methylated in promoter region that can lead to silencing and decreased transcription?

CpG island

6

What is methylated in prokaryotic DNA replication to allow for mismatch repair enzymes to distinguish between old and new prokaryotic strands?

Cytosine and Adenine

7

5 parts needed for purine synthesis

Glycine, aspartate, glutamine ("PURe girls still gag"), THF, CO2

8

2 parts needed for pyrimidine synthesis

Carbomyl phosphate, aspartate

9

What is carbomoyl phosphate derived from?

Glutamine + CO2

10

Nucleoside vs Nucleotide?

Nucleoside-base + (deoxy)ribose
Nucleotide-base + (deoxy)ribose + phosphate; linked by 3'-->5' phosphodiester bond

11

Cytosine deamination-->

Uracil

12

Thymine has a ______

Methyl group

13

Guanine vs. Adenine?

Guanine has a =O and can be thought of as "OG"

14

Rings in purines?

2 rings

15

Rings in pyrimidines?

1 ring

16

Rate limiting step for pyrimidine production

Glutamine+ CO2-->Carbomyl phosphate (via CPS II)

17

Leflunomide inhibits...

Dihydroorotate dehydrogenase

18

Mycophenolate and ribavirin inhibit..

IMP dehydrogenase

19

Hydroxyurea inhibits..

ribonucleotide reductase

20

6 MP and its prodrug azothioprine inhibits...

de novo purine synthesis

21

5 FU inhibits

Thymidilate synthase

22

Metotrexate, Trimethoprim, and pyrimethamine inhibit...

DHF reductase

23

How are ribonuclotides converted to deoxyribonucleotides?

ribonucleotide reductase

24

Draw the purine/pyrimidine synthesis pathway

p. 63 FA

25

What is the salvage pathway for thymidylate synthase inhibition?

Thymidine kinase requires thymidine supplementation and normally accounts for 5-10% of dTMP synthesis

26

Draw the purine salvage pathway

p. 64 FA

27

Inheritance of adenosine deaminase deficiency?

Auto recessive

28

Inheritanc of Lesch nyhan syndrome?

X-linked recessive

29

symptoms of HGPRT deficiency

Hyperuricemia, Gout, Pissed off (aggression, self mutilation) Retardation, DysTonia

30

Treatment for HGPRT?

Can't treat other symptoms but can treat hyperuricemia/gout with allopurinol and febuxostat

31

Each codon specifies only 1 amino acid

Unambiguous

32

Most amino acids are coded by multiple codons?

Degenerate/redundant

33

What are the exceptions to AA being coded by multiple codons?

Methionine (AUG)
Tryptophan (UGG)

34

What is commaless, nonoverlappying genetic code?

Read from a fixed starting point as a continuous sequence of bases (exception: viruses)

35

What is a universal genetic code?

genetic code convserved throughout evolution (exception: mitochondria)

36

2 enzymes that increase activity of de novo purine synthesis?

PRPP synthetase (Ribose 5-Phosphate-->PRPP) and PRPP amidotransferase (PRPP-->5-phosphoribosylamine)

37

Rate limiting enzyme of purine synthesis

Glutamine PRPP amidotransferase

38

Carbon sources in purine synthesis?

Glycine, THF, CO2 (Aspartate, glutamine nitrogen sourceS)

39

Consensus sequence of base pairs in genome where DNA replication begins. Difference in prokaryotes and eukaryotes?

Origin of replication
Multiple (eukaryotes), single (prokaryotes)

40

Y-shaped region along dna template where leading and lagging strands are synthesized

Replication fork

41

Unwinds DNA template at replication fork

Helicase

42

Prevents strands from reannealing after unwinding

Single-stranded binding proteins

43

Create a single-or double-stranded break in the helix to add or remove supercoils

DNA topoisomerases

44

How do replication forks travel?

Travel bidirectionally away from origin of replication as DNA polymerase synthesizes complementary daughter DNA strands

45

Makes an RNA primer on which DNA pol III can initiate replication

Primase

46

What is ori identified and bound by that locally allows it do dissociate from dsDNA into ssDNA?

DNA A protein. SSB proteins then bind to ssDNA and stabilize and prevent premature reannealing. Helicase then binds ssDNA at ori, moves into rep fork and proceeds to seperate and unwind DNA

47

What protein triggers DNA replication in bacteria?

DNA A

48

5'-->3' synthesis on leading and lagging strand (until reaches primer of preceeding fragment) and proofreads with 3'-->5' exonuclease

DNA polymerase III

49

5'-->3' synthesis of leading and lagging strand with 3'-->5' exonuclease and also excises RNA primer with 5'-->3' exonuclease+repair of damaged parent DNA

DNA polymerase I

50

Catalyzes formation of phosphodiester bond within a strand of dsDNA (ie. joins Okazaki fragments)-->seals

DNA ligase

51

RNA dependent DNA polymerase (reverse transcriptase) that adds DNA to 3' ends of chromosomes to avoid loss of genetic material with every duplication?

Telomerase

52

Inhibit prokaryotic enzyme topoisomerase II (DNA gyrase) and topoisomerase IV

Fluoroquinolones

53

Makes up DNA helicase and primase complex

Primosomes

54

Coes for tRNA and rRNA and resembles bacterial (prokaryotic) chromosome

Mitochondrial DNA (small circular chromosome similar to bacterial chromosome)

55

What is an exonuclease?

Removes nucleotides at the end of DNA molecule so it has a particular direction

56

Sequence added to 3' DNA ends of chromosomes

TTAGGG

57

Telomeres are expressed in what 3 types of cells

Stem cells-long telomeres and act ve telomerase, telomeres shorten with each cell division
Cancer cells-upregulate telomerase activity, preventing cell death by maintaining length of telomeres. Cancer cells immportal b/c cells continue to divide w/o aging and shortening of telomeres
Somatic cells-terminally differentiated and

58

Transversion and transition apply to which type of mutations?

Point mutations (silent, missence, nonsence)

59

Transition mutation

purine to purine or pyrimidine to pyrimidine "same"

60

Transversion mutation

purine to pyrimidine or pyrimidine to purine

61

Sickle cell disease is a type of what mutation and what happens?

Point mutation that is missence (GAG (glutamic acid) substitution with GTG (valine))

62

Where is the base change in a silent mutation?

Often base change in the 3rd position of codon (tRNA wobble)

63

What is it called if new AA is similar in structure to old in missence mutation?

Conservative

64

Duchenne muscular dystrophy is what type of mutation?

Frameshift mutation (deletion of dystrophin gene)

65

Slapped strand mispairing can lead to what?

Insertion and frameshift mutation

66

What causes the formation of a larger nonfunctional protein, but usually the immunoreactivity of normal proteins (i.e.binding to antibodies?

Splice site mutations (type of point mutation) where mutation of splice sites (not removing all introns from hnRNA in formation of mature mRNA). This is a type of point mutation

67

Eukaryotic lagging strand building

DNA pol. alpha

68

Eukaryotic leading strand building

DNA pol. delta

69

Eukaryotic DNA repair (specifically base excision repair)

DNA pol. beta

70

replicates mitochondrial DNA

DNA pol. gamma

71

Mechanism defective in xeroderma pigmentosum

nucleotide excision repair

72

Repair important in spontaneous/toxic deamination

base excision repair

73

Mechanism defective in HNPCC

Mismatch repair

74

Mechanism defective in ataxia telangiectasia; fanconi anemia

Nonhomologous end joining

75

What is an endonuclease?

Cut DNA specific DNA sequences within the molecules with no particular direction

76

When does nucleotide excision repair occur and when does base excision repair occur and when does mismatch repair occur?

G1 phase-NER
Throughout cell cycle-BER
G2 phase-Mismatch repair

77

Steps in nucleotide excision repair

Specific endonucleases release oligonucleotides by creating a nick on either side. DNA polymerase and ligase fill and reseal gap respectively.

78

Steps in base excision repair

Base-specific glycosylase (specific endo nuclease) removes base creating an AP site. Following that, one or more nucleotides are removed via AP endonuclease on 5' end and lyase and 3' end. After that DNA polymerase beta adds DNA and is sealed via ligase.

79

Steps in mismatch repair

Newly synthesized strand is recognized. Mismatched nucleotides are removed. Gap is filled and resealed.

80

Cause and symptoms of xeroderma pigmentousm?

Most commonly due to absence of UV-specific endonuclease. This is responsible for normally excising thymine dimers by nicking the strand at the thymine dimer.
Symptoms include photosensitivity, poilkiloderma, and hyperpigmentation in sun exposed areas--> increase risk of skin cancer

81

What brings together 2 ends of DNA fragments to repair ds breaks?

Nonhomologous end joining

82

DNA and RNA is synthesized in what direction?
mRNA is read in what direction?
Protein synthesis?

5'-->3'
5-->3'
N terminus-->C terminus

83

What is the mechanism behind drugs that block DNA replication?

modified 3' OH, preventing addition of next nucleotide (i.e. cant attach 5' end triphosphate)--> "chain termination"

84

Mutations in what 2 genes account for 90% of lynch syndrome?

MSH2 and MLH1 genes code for MutS and Mut L homologs. Normally, mismatch repair beings with MutS homolog detecting a mis-match on new daughter strand, which is distinguished from parent strand with occasional nicks in phosphodiester bonds. Mut L recruited slides along complex until nick is recgonized. Exonuclease I loaded onto and activated by repair complex. Daughter strand degraded. DNA pol. delta creates new strand and ligase seals

85

mRNA start codons (eukaryotes vs. prokaryotes)

Eukaryotes-codes for methionine, which may be removed before translation is completed
Prokaryotes-codes for N-formylmethionine (fMet). fMet stimulates neutrophil chemotaxis.

86

RNA pol binding?

Promoter region

87

CAP binding in lac operon (prokaryotic)

At CAP site upstream of promoter

88

lac l transcribes?

Repressor protein (known as regulatory gene)

89

lac z codes for?

B-galactosidase (responsible for hydrolysis of lactose into glucose and galactose)

90

lac y codes for?

Permease (allowing lactose to enter bacterium)

91

lac A encodes?

B galactosidease transacetylase

92

Repressor protein binds to (prokaryotic)?

operator region

93

Toxin Inhibits RNA pol II and side effect?

a-amanitin (found in amanita phalloides death cap mushrooms)
Severe hepatotoxicity (increase ALT, AST, bilirubin)

94

Inhibits RNA pol in prokaryotes

Rifampin

95

Inhibits RNA pol in eukaryotes and prokaryotes

Actinomycin D

96

What opens DNA at promoter site?

RNA pol II

97

What are specific foci involved in mRNA regulation/turnover in the cytoplasm?

P bodies

98

Antibodies to spliceosomal snRNPs

Anti-smith antibodies in SLE

99

Anti-U1 RNP antibodies

MCTD

100

Single gene coding for multiple proteins when same gene is organized differently in different tissues

Alternative splicing

101

Abnormal splicing variants implicated in what?

Oncogenesis, genetic disorders (B-thalassemia)

102

3' end of tRNA

CCA

103

D arm (dihydrouracil residues)

Recognizes specific aminoacyl tRNA synthetase for each AA

104

T arm (thymine, psuedouracil, cytosine)

Recognizes sequence necessary for tRNA-ribosome binding

105

Hsp60 in yeast is example of a?

Chaperone protein (facilitating and/or maintaining protein folding)

106

What helps incoming tRNA bind to A site?

elongation factors

107

What catalyzes peptide bond formation, transferring growing peptide to AA in A site?

rRNA ("ribozyme") mediates peptidyl transferase activity

108

How does prokaryotic protein synthesis begin and what is first step for initiation?

mRNA (Shane-Dalgarno sequence) binds to complementary to 16S rRNA (part of 30S ribosomal subunit) and this is necessary for initiation of protein translation.

109

AA linked by covalent peptide bonds

Primary structure

110

alpha helix, B-sheet

Secondary structure

111

Compact folding of secondary structure with ionic hdyrophobic hydrogen disulfide stabilizing

Tertiary structure

112

Arrangement of multiple folded protein into a multi-subunit complex

Quarternary structure

113

Constitutive and inactive regulation of cell cycle

CDKs

114

Regulatory proteins that control cell cycle events; phase specific

Cyclins

115

Phosphorylate other proteins to coordinate cell cycle progression; must be activated and inactivated at appropriate times for cell cycle to progress

Cyclin-CDK complexes

116

2 cells rich in RER

Mucus-secreting goblet cells of small intestine and antibody-secreting plasma cells

117

3 cells rich in SER

Liver hepatocytes, steroid hormone producting cells of adrenal cortex, gonads

118

Functions in lipid synthesis and carbohydrate metabolism

SER

119

Functions in synthesis of proteins (exported)

RER

120

Two subunits of ribosomes?

Small unit-binds mRNA (template for protein synthesis) and tRNA (carry amino acids)
Large unit-contains peptidyl transferase (catalyzes peptide bond formation in AA)

121

Membrane enclosed organelle involved in catabolism of very-long chain fatty acids, branched-chain fatty acids, and amino acids

Peroxisomes

122

Degrades damaged or uibiquitin-tagged proteins.

proteosome

123

Defects of ubiquitin proteoasome system in what disease?

Parkinson disease

124

N-oligosaccharides on what in post translational modification?

Asparagine amino group

125

O-oligosaccharides on what in post translational modification?

serine and threonine hydroxyl group

126

Mechanism for coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes

Failure of golgi to phosphorylate mannose residues on glyocoprotins so proteins are not delivered to lysososomes.

127

COP I

Golgi-->Golgi (Retrograde); cis golgi-->ER

128

COP II

ER-->cis-golgi (anterograde)

129

Clathrin

trans golgi-->lysosomes; plamsa membrane-->endosomes

130

Which AA can be modified by the golgi apparatus?

Asparagine, serine, threonine

131

Cyclin D binds to what?

CDK4-->phosphorylation of Rb protein-->Rb protein is released from transcription factor E2F-->w/ E2F unbound, cell is free to transcribe/synthesize components needed for progressing THROUGH S phase (DHF, cyclin E, thymidilate synthase, DNA polymerase)

132

Cyclin E binds to what?

CDK2-->allows progression INTO S phase.

133

Cyclin A binds to what?

CDK2 to allow progression from G2-->M (mitotic prophase)

134

Cyclin B binds to what?

CDK1 complex activated by Cdc 25-->breakdown of nuclear lamnins (skeletal framework) and initiation of mitosis

135

Nuclear localization signals rich in what AA?

Proline, Arginine, Lysine (PAL). Makes sense b/c histones are in nucleus and rich and lysine and arginine

136

What are the sorting centers of the cell?

Endosomes. For material from outside of cell or from Goligi, sending it to lysosomes for destruction or back to membrane/golgi for further use.

137

Stain: Vimentin
Cell type: ?

Connective tissue (stain used to identify sarcoma)

138

Stain: Desmin
Cell type?

Muscle (stain used to identify rhabdomyosarcoma for example)

139

Stain: Cytokeratin
Cell type?

Epithelial cell (cell used to identify carcinoma)

140

Stain: GFAP
Cell type?

Neuroglia (Astrocytoma)

141

Stain: Neurofilaments
Cell type?

Neurons (specifically axons. used to identify neuroblastoma)

142

Predominant function of microfilaments?

Muscle contraction, cytokinesis

143

Predominant function of intermediate filaments?

cell structure

144

Predominant function of microtubules?

Cell division, movement

145

Drugs that act on microtubules?

Mebendazole, Griseofulvin, Colchicine, Vincristine/Vinblastine, Paclitaxel (Microtubules Get Constructed Very Poorly)

146

ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets

Axonemal dynein

147

MOA of Ouabain?

Inhibits Na+ K+ ATPase by binding to K+ site.

148

Most abundant protein in human body

collagen

149

Inhibited by scurvy?

hydroxylation of specific proline and lysine residues

150

OI has problems forming what?

problems forming triple helix (procollagen)

151

Ehlers danlos, menkes disease has problems with what?

Cross-linking tropocollagen molecules to make collagen fibrils (secondary to lysyl oxidase covalently linking lysine-hydroxylysine cross-linkage)

152

Mature collagen is synthetized in what cells?

Fibroblasts, osteoblasts, and chondroblasts

153

Most abundant AA in collagen?

Glycine

154

What catalyzes cleavage of disulfide rich terminal regions of procollagen?

Extracellular precollagen peptidases

155

2 components of bone matrix

Inorganic hydroxyapatite crystals and organic type I collagen

156

Common mutations leading to ehlers danlos phenotypes include deficiencies in what two enzymes?

Lysyl hydroxylase (characteristic of kyphoscoliosis and ocular fragility) and pro-collagen peptidase (joint laxity, loos skin, and easy bruising)

157

3 major differences between collagen and elastin?

1) Very few proline, lysine residues hydroxylated in elastin (thought of as rich in nonhydroxylated proline, glycine, and lysine
2) Triple helix in collagen. No triple helix in elastin
3) Triple helix formation in collagen is initiated by hydroxylation, glycosylation, and inter-chain disulfide bridges @ C-terminus of procollagen. These modifications not happen in elastin molecules

158

Enzyme catalyzing elastin b linking vs collagen cross linking

Lysyl hydroxylase vs lysyl oxidase

159

What is unique about elastin crosslinking?

Unique form of desmosine crosslinking between 4 lysine residues between 4 different elastin chains.

160

Southern blot

DNA sample cleaved into smaller pieces (restriction endonuclease). Electrophoresed on gel. Transferred to filter and filter soaked in denaturant, which is than labeled by DNA probe that recognizes and anneals to complementary strand

161

Northern blot

Similar to Southern blot except RNA sample is electrophoresed and recognized by DNA probe

162

Western blot

Sample protein via gel electrophoresis and labeled antibody used to bind relevant protein

163

Southwestern blot

DNA binding proteins (TF, histones, nucleases) used labeled oligonucleotide probes

164

Describe HIV confirmatory test

Western blot. Antibodies to gp41, gp120/160, p24. Two positive necessary for confirmed positive diagnosis

165

Direct ELISA used for?

Test for antigen in patient blood

166

Indirect ELISA used for?

Test for antibody in patient blood

167

Constitutive insertion

Random insertion of gene into mouse genome

168

Conditional insertion

Targeted insertion or deletion of gene thorugh recombination with mouse gene

169

Inducibly manipulate genes at specific developmental points

Cre-lox system

170

dsRNA is synthesized that is complementary to the mRNA sequence of interest. When transfected into human cells., dsRNA seperates and promotes degradation of traget mRNA, "knocking down" gene expression

RNA interference.

171

What explains variable expression in mitochondrially inherited disease

Heteroplasmy due to presence of both normal and mutated mtDNA.

172

Mccune albright syndrome is an example of

somatic mosaicims that arises from mitotic errors after fertilization and propagates through multiple tissues or organs

173

4 assumptions of hardy weinberg

No net migration, no mutation at locus, completely random mating, natural selection is not occuring

174

X-linked recessive diseases:

"Oblivious female will give her boys x-linked disorders"
Ocular albinism, fabry disease, wiskott-aldrich, g6pd deficiency, hunter syndrome, bruton agammaglobulinemia, hemophilia A+B, lesch nyhan, duchenne muscular dystrophy

175

Hypophosphatemic rickets inheritance

x-linked dominant

176

Lifraumeni syndrome commonly causes:

SBLA cancer: sarcoma, brain/breast, leukemia, adrenal gland cancers

177

Deletion of what 3 nucleotides in cystic fibrosis coding for what?

Phe at position 508

178

Quad screen Downs, Edwards, Patau?

Down: Increase B-hCG, Decrease afp, decrease estriol, increase inhibin A
Edwards: Decrease b-hCG, decrease afp, decrease estriol, decrease or normal inhibin A
Patau: decrease bCG decrease PAPPA and increase nuchal translucency in 1st trimester screening (not quad screen)

179

Chromosome 3 disorders

VHL, renal cell carcinoma

180

Chromosome 4 disorders

ADPKD with PKD2 defect, Huntington disease

181

Chromosome 5 disorder

Cri-du-chat syndrome, FAP

182

Chromosome 7 disorders

williams syndrome, cystic fibrosis

183

Chromosome 9 disorder

Fredreich ataxia

184

Chromosme 11 disorder

Wilms tumor

185

Chromosome 13 disorder

Patau syndrome, wilson disease

186

Chromosome 15 disorder

Prader-willi, angelman

187

Chromosome 16 disorder

ADPKD with PKD1 defect

188

Chromosome 17 disorder

NF1

189

Chromsome 18 disorder

Edwards

190

Chromsome 21 disorder

downs

191

Chromsome 22

nf2, digeorge

192

X chromosome

Fragil x, klinefelter, x-linked agammaglobulinemia

193

what 5 chromosome pairs do robertsonian translocation occur in?

13,14,15,21,22

194

Trinucleotide expanision
Fragile X
Fredreich ataxia
Hungtinton
Myotonic dystrohy

CGG
GAA
CAG
CTG