DNA basics Flashcards

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1
Q

Nucleosome core consists of what histones?

A

H2A (2)
H2B (2)
H3 (2)
H4 (2)

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2
Q

Histones are positively charged due to what

A

Lysine
Arginine

Allows association with negatively charged DNA

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3
Q

Deamination of cytosine results in what chemical?

A

Uracil

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4
Q

How many H bonds between C+G

A+T?

A
C+G = 3 (Cee and Gee has Three)
A+T = 2
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5
Q

What kind of composition results in higher melting temperature in DNA?

A

More C+G bonds = higher melting temperature due to three hydrogen bonds per C+G bond

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6
Q

Amino acids required for purines?

A

Glycine
Aspartate (I always confuse with the other ‘A’)
Glutamine (not -ate, glutamINE)

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7
Q

Vitamin required for purine synthesis?

A

tetrahydrofolate (active form of folate)

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8
Q

Sources of Carbons in Purines?

A

Glycine
Tetrahydrofolate
CO2

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9
Q

Sources of Nitrogens in Purines?

A

GlutamiNe

Aspartate

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10
Q

Needed to make pyrimidines:

A
Aspartate
Carbamoyl phosphate (CO2, Glutamine, ATP)
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11
Q

Describe chemical structure of CARBAMOYL PHOSPHATE

A

1 carbon, 1 nitrogen

Central carbon with 3 bonds. (comes from CO2)
A bond with NH2 (N comes from glutamine)
A double bond with Oxygen
And a bond with a Phosphate group (from ATP)

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12
Q

Synthesis of what nucleotide requires ATP?

A

Pyrimidines

Carbamoyl phosphate has 1 phosphate group that phosphorylates

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13
Q

Sources of nitrogen in pyrimidines

A

glutamine

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14
Q

Sources of phosphate in pyrimidines

A

ATP

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15
Q

Sources of carbon in pyrimidines

A

CO2

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16
Q

Drug inhibiting dihydrofolate reductase

A

Prokaryotes: trimethoprim
Eukaryotes: methotrexate

17
Q

Drug inhibiting thymidylate synthase

A

5-fluorouracil

18
Q

Drug inhibiting ribonucleotide reductase

A

Hydroxyurea (sickle cell, cancer)

19
Q

Autosomal recessive disease: deficiency of UMP synthase

A

Orotic aciduria

No conversion of oritic acid to UMP

Elevated orotic acid in urine
Ammonia blood levels normal

20
Q

Elevated orotic acid + hyperammonemia

A

Ornithine transcarbamoylase deficiency (OTC deficiency)

21
Q

Elevated orotic acid, with NO hyperammonemia

A

Orotic aciduria

22
Q

Megaloblastic anemia

A

B12, Folate deficiency

If no response to B12, Folate supplementation, think of:
Pyrimidine synthesis disorder (orotic aciduria)
DNA synthesis disorders
Toxins, drugs (methotrexate, 6-mercaptopurine, phenytoin, NO)

23
Q

Treatment for Orotic aciduria

A

Supplemental dietary uridine

Since UMP synthase is deficient, bypass this step.

24
Q

Drug that inhibits Glutamine PRPP Amidotransferase?

What process is disrupted?

A

6-mercaptopurine disrupts production of IMP in PURINE SYNTHESIS

25
Q

Drug that inhibits IMP dehydrogenase?

What chemical deficiency results?

A
Mycophenolate
GMP synthesis (from IMP) is disrupted
26
Q

Purine de novo synthesis RLE?

A

Glutamine PRPP amidotransferase

27
Q

Pyrimidine synth. RLE?

A

Carbamoyl phosphate synthase II (CPSII)

28
Q

Drugs METABOLIZED BY xanthine oxidase?

A

azathioprine
6-mercaptopurine

THEREFORE: inhibiting XO results in increased toxicity of THESE DRUGS

29
Q

Drugs inhibiting xanthine oxidase?

A

Allopurinol
Febuxostat

Patients on these drugs are susceptible to INCREASED azathioprine or 6-mercaptopurine toxicity.

30
Q

Xanthine oxidase inhibition results in decreased metabolism of these drugs.

A

azathioprine

6-mercaptopurine

31
Q

Deficiency of HGPRT

A

Lesch-Nyhan Syndrome

Hypoxanthine, Guanine are NOT recycled to IMP, GMP –> resulting in overproduction of URIC ACID

32
Q

Findings in Lesch-Nyhan Syndrome:

A
Gout
CNS problems:
Intellectual disability
Aggressive behavior
Self-mutilation (lip biting)
Choreoathetosis
33
Q

Treatment of Lesch-Nyhan Syndrome:

A

allopurinol (treats gout)

Cannot treat CNS features.

34
Q

Adenosine deaminase deficiency results in what

A

SCID

35
Q

What cells are affected in SCID?

A

T-cells and B-cells

36
Q

Clinical triad of SCID?

A

Severe recurrent infections
Chronic diarrhea
Failure to thrive
*no thymic shadow of newborn x-ray

37
Q

What accounts for negative charge in DNA?

A

phosphate groups