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Integrated - Block 1 Exam 1 > BCH - Samuelson lec 8/13 part 1 > Flashcards

BCH - Samuelson lec 8/13 part 1 Flashcards

1
Q

Nucleic acids relevance to life - function?

A

organism maintenance

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2
Q

What are nucleic acids

A

molecules of information

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3
Q

what are the 2 types of nucleic acids

A

RNA (ribonucleic acid) and DNA (deoxyribonucleic acid)

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4
Q

What do nucleic acids contain

A
  1. pentose sugar (ribose, 2’-deoxyribose)
  2. phosphate (mono, di or tri)
  3. Base (purine or pyrimidine)
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5
Q

Nomenclature wise, what is a nucleotide

A

Sugar + base + phosphate

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6
Q

Nomenclature wise, what is a nucleoside

A

sugar + base

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7
Q

How are bases numbered

A

with numbers

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8
Q

how is sugar numbered

A

primed numbers (3’)

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9
Q

how are phosphates numbered

A

alpha, beta, gamma

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10
Q

What are the 2 types of sugar backbones (DNA/RNA)

A
  1. Nucleotides in DNA/RNA
  2. Phosphates (mono, di, tri)
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11
Q

What are the 2 types of sugars in nucleotides

A

Ribose (RNA) and 2’-deoxyribose (DNA)

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12
Q

What are the 2 types of bases in DNA and RNA

A

Purines and Pyrimidines

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13
Q

The purines?

A

A and G

pure As Gold

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14
Q

The pyrimidines?

A

C, U, T

Cut the PY

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15
Q

Where is Adenine found

A

DNA and RNA

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16
Q

Where is Guanine found

A

DNA and RNA

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17
Q

Where is Cytosine found

A

DNA and RNA

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18
Q

Where is Uracil found

A

RNA

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19
Q

Where is Thymine found

A

DNA

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20
Q

Phosphodiester bonds link nucleotides to form

A

nucleic acids

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21
Q

Nucleic acids - strong acids, example?

A

Phosphate group pKa of ~1

Gives a negative charge

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22
Q

Nucleic acids are polymers of

A

nucleotides

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23
Q

DNA is a polymer of

A

deoxyribionucleotides

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24
Q

RNA is a polymer of

A

ribonucleotides

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25
Q

DNA is most often used as the genetic material, explain how

A

Stability - double helix

Copying mechanisms (exception: RNA viruses)

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26
Q

DNA Structure - polarity

A

nucleotides are joined by a 5’-3’ phosphodiester linkage

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27
Q

What direction is DNA and RNA written

A

5’ –> 3’

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28
Q

The backbone of the nucleic acid strands are alternating

A

pentose and phosphates

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29
Q

Explain DNA being double stranded

A

Two polymer strands running anti-parallel and are COMPLEMENTARY

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30
Q

Most common form of DNA

A

B form (right)

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31
Q

Chargraff’s rule?

A

amount of purines (AG) = pyrimidines (CT) and A = T and G = C

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32
Q

Double helix is held together by?

A

hydrogen bonds between complementary base pairs

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33
Q

Force stabilizing nucleic acid structures?

A

G-C: 3 hydrogen bonds
A-T: 2 hydrogen bonds

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34
Q

Physical properties of DNA - explain melting

A

DNA can melt/denature which means it becomes single stranded

This happens when the temperature is increased

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35
Q

Physical properties of DNA - explain anneal / hybridize

A

The double stranded form is energetically more favorable under mild conditions, so double helix forms SPONTANEOUSLY

Complementary strands reanneal

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36
Q

Base composition and DNA - what is it?

A

It affects melting temperature

Tm = the temperature at which half the DNA is denatured to a single stranded state

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37
Q

Hyperchromic effect

A

striking absorbance increases as DNA denatures or melts

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38
Q

Biological Consequences and Biotechnial Utility of DNA Structural Properties - name the 3

A
  1. each strand is template for other strand - DNA replication and DNA repair
  2. DNA is used to store, disseminate, and pass on information
  3. Nucleic acid sequences can be determined
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39
Q

How is DNA packaged inside a nucleus

A

by wrapping DNA around a protein core

this base unit is a nucleosome

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40
Q

Discuss the details of DNA being packaged inside a nucleus

A

Chromatin = DNA and protein core

Protein core made up of histones
- core histones: H2A, H2B, H3, H4
-linker histone: H1

Histones are highly basic (positively charged) mainly because high amount of Lysine

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41
Q

Chromatin Structure

A

Supercoiling of Chromosomal DNA starts with nucleosome, but there are increasing levels of supercoiling to produce chromatin

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42
Q

Nucleotide Synthesis - nucleotides are the monomers of

A

nucleic acids

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43
Q

What are the 2 metabolic sources of nucleotides

A

De novo biosynthesis

Salvage

44
Q

Explain de novo biosynthesis

A

Almost ALL organisms synthesize nucleotides

Purines: amino acids, bicarbonate, tetrahydrofolate, energy

Pyrimidines: amino acids, bicarbonate, energy

45
Q

Explain salvage

A

Turnover or recycling of cellular nucleic acids

Digestion of ingested nucleic acids

46
Q

What is PRPP synthetase

A

enzyme responsible for the synthesis of activated ribose which is necessary for de novo synthesis of purine and pyrimidine nucleotides

47
Q

PRPP is required for

A

synthesis of both purines and pyrimidines and nucleotide salvage

48
Q

Purine Biosynthesis - what do amino acids provide

A

the “Ns”
Glutamine 2N
Aspartate 1N
Glycine 1N, 2C

49
Q

Purine Biosynthesis - committed step?

A

Glutamine-PRPP amidotransferase

50
Q

Purine Biosynthesis - first nucleotide?

A

Inosinate or Inosine monophosphate (IMP)

51
Q

What is IMP converted to

A

A and G

52
Q

What do IMP, AMP, and GMP depend on

A

GTP

53
Q

How is purine nucleotide biosynthesis regulated

A

IMP pathway control points and Branch point control

54
Q

Explain IMP pathway control points

A
  • feedback inhibition
    —ADP and GDP
  • Feedforward activation
    —allosteric activation by PRPP
55
Q

Explain branch point control

A

Rates of AMP and GMP are coordinated

AMP and GMP are competitive inhibitors of IMP

56
Q

Key points of purine ribonucleotide synthesis

A
  1. purines are synthesized by assembling a purine base on PRPP, a molecule produced from R5P and ATP
  2. IMP is the first purine nucleotide synthesized
  3. PRPP, amino acids, folate, and ATP are used to synthesis purines
  4. AMP and GMP are synthesized from IMP. The biosynthesis of ATP and GTP are reciprocally regulated by the concentration of the other
  5. Kinases convert AMP and GMP to ATP and GTP
  6. Purine synthesis is regulated by feedback inhibition and feedforward activation to maintain a concentration of purines. Branchpoint control regulation is used to maintain a balance of each purine
57
Q

Pyrimidine Biosynthesis - 6 steps to UMP, what are they?

A

Carbamoyl phosphate, carbamoyl aspartate, dihydroorotate, orotate, OMP, UMP

58
Q

When is PRPP added in pyrimidine biosynthesis

A

with Orotate

59
Q

What gets added to PRPP in pyrimidine biosynthesis

A

OMP

60
Q

De novo Biosynthesis ingredient list

A

Glutamine, aspartate, HCO3- (bicarbonate), energy (ATP), PRPP - activated sugar

61
Q

Pyrimidine biosynthesis steps

A

HCO3- + glutamine + 2 ATP –> carbamoyl phosphate + 2 ADP + Pi + glutamate

62
Q

Pyrimidine Biosynthesis (U and C) - 1st pyrimidine?

A

Orotate

63
Q

Steps of pyrimidine biosynthesis (U and C)

A

Orotate (add PRPP) –> OMP –> UMP –> –> UTP (glutamine and ATP added) –> CTP

64
Q

Remember we get CTP from

A

UMP

65
Q

Animal pyrimidine biosynthesis - explain

A

Feedback inhibition to prevent energy use

66
Q

Animal pyrimidine biosynthesis - what is PRPP doing

A

feedback activation

67
Q

Convergence of Purine and Pyrimidine Nucleotide Biosynthesis to make dNTPs - know how to draw!!!!

What does RR stand for?

A

RR = ribonucleotide reductase: 1 enzyme produces 2’-deoxy (d) ribonucleoside diphosphate: dADP, dGDP, dCDP, and dUDP

68
Q

Synthesis of 2’-deoxy-ribonucleotides for DNA

A

a. catalyzed by ribonucleotide reductase (RR)
b. NDP is reduced (2’ position) to form the dNDP
c. NADPH provides reducing power, via a protein intermediate, thioredoxin (glutaredoxin can be used in place of thioredoxin)

69
Q

Regulation of dNTP synthesis - goal of RR enzyme regulation?

A

to produce correct ratios of the 4 dNDPs

70
Q

Regulation of dNTP synthesis doesn’t make what

A

dTTP

71
Q

Ribonucleotide Reductase

A

regulation of overall activity (reaction velocity)

regulation of substrate specificity (which substrate binds) –> look at picture it is slide 50

72
Q

Thymidylate synthase and thymidine kinase make what together from dUMP

A

dTTP

73
Q

Production of Deoxythymidine - for DNA only

A

a. Add methyl group to dUMP!
b. methyl donated by N5, N10
c. no ribothymidylate so dTMP, dTDP, dTTP used, always deoxy, which are often written as TMP, TDP, and TTP!

74
Q

Folate derivative acts as 1 carbon donor –>

N5, N10 - methylene-tetrahydrofolate must be regenerated by

A

Dihydrofolate reductase, a key enzyme in the biosynthetic production of dTMP

75
Q

Nucleotide salvage and degradation summed up

A

Nucleotide salvage = reuse of bases

Nucleotide degradation = catabolize bases

76
Q

Nucleotide Metabolism - nucleotides and phosphates yield

A

nucleosides

77
Q

Nucleosides are absorbed through

A

the intestine or further degraded by nucleosidases and nucleoside phosphorylases

78
Q

Nucleotide Degradation

A

Purines are broken down to uric acid

Pyrimidines are converted to CoA derivatives for catabolism

79
Q

Nucleotide degradation and salvage - purine degradation (end product Uric acid)

A

Degradation proceeds by removing base from
nucleotides, then sugars.

Deficiency of adenosine deaminase causes SCIDs
(bubble boy, gene therapy)

80
Q

Nucleotide degradation and salvage - purine salvage (recycling of bases)

A

Bases added to PRPP by HGPRT (HPRT)

Deficiency of HGPRT (HPRT) causes Lesch-Nyhan
syndrome, lethal disease.
-Uric acid crystals
-feedback inhibition PRPP synthase causing deficiency in all nucleotides

81
Q

Purine Salvage - free purines are reconverted to

A

corresponding nucleotides

82
Q

Explain gout

A

Gout is the excess of uric acid

purines are broken down to uric acid

Allopurinol treats gout by irreversibly inhibiting xanthine oxidase which inhibits hypoxanthine from producing uric acid

83
Q

Chemotherapy - cytotoxic

A

kills dividing cells

84
Q

Antimetabolite Drugs: not just for cancer therapy, list the 4 drugs

A

6-mercaptopurine

Allopurinol

Fluorouracil

Methotrexate

85
Q

Antimetabolite Drug: 6-mercaptopurine use?

A

acute lymphocytic leukemia (ALL)

86
Q

Antimetabolite Drug: Allopurinol

A

Gout

87
Q

Antimetabolite Drug: Fluorouracil

A

Anticancer

88
Q

Antimetabolite Drug: Methotrexate

A

Anticancer autoimmune

89
Q

Chemical structure of methotrexate

A

folate analog

90
Q

chemical structure of 6-mercaptopurine

A

purine analog

91
Q

What is 5-Fluorouracil used for

A

it is an antimetabolite used to treat cancer

92
Q

Drug administration of 5 fluorouracil

A

Drug administered must be converted to 5F-dUMP to be efficacious

93
Q

5 FU and methotrexate inhibit synthesis of

A

dTMP

94
Q

List the 4 multi-drug cocktails that are used to treat cancer

A

ABVD, CHOP, FOLFOX, TIP

95
Q

DNA damage response

A

apoptosis - programmed cell death

96
Q

Chemotherapeutic drugs - DNA damaging agents

A

bleomycin, cyclophosphamide, dacarbazine, melphalan, chlorambucil, carboplatin/cisplatin, temozolomide

97
Q

What is the therapeutic index

A

Drug selectivity, which leads to therapeutic indices larger than 1, implies that cancer cells are hypersensitive to a therapeutic agent

Lack of selectivity and the absence of a significant therapeutic index simply imply that cancer cells are as sensitive to an agent as are cells in normal tissues

98
Q

Chemoresistance Mechanism?

A

Increased DNA repair

99
Q

DNA repair pathways, common damaging agents? (2)

A

Alkylating agents and Ionizing Radiation

100
Q

Ionizing Radiation DNA Damage - Xrays

A

Low LET (linear energy transfer)

single-strand breaks caused by X-rays for example

101
Q

Double stand DNA damange

A

A non-damaged chromosome can be used to repair its double-strand DNA damaged homologous chromosome

102
Q

Homology directed repair (HDR) of double-strand DNA damage - inherited mutations

A

Inherited mutations in BRCA1 or BRCA2 greatly increase lifetime risk of developing breast and ovarian cancer

103
Q

Homology directed repair (HDR) of double-strand DNA damage - uses recombination ?

A

Uses recombination between DNA of the
undamaged and damaged homologous chromosomes to repair the damaged chromosome

104
Q

IMP + GTP = ?

A

AMP (adenosine monophosphate)

105
Q

IMP + ATP = ?

A

GMP (guanosine monophosphate)

106
Q

The genetic code is used to

A

translate information stored in DNA into proteins

107
Q

the genetic code is

A

evolutionary conserved

Integrated - Block 1 Exam 1 (5 decks)

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