DNA basics

Question 1

Nucleosome core consists of what histones?

Answer 1

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

Question 2

Histones are positively charged due to what

Answer 2

Lysine
Arginine

Allows association with negatively charged DNA

Question 3

Deamination of cytosine results in what chemical?

Answer 3

Uracil

Question 4

How many H bonds between C+G

A+T?

Answer 4

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

Question 5

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

Answer 5

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

Question 6

Amino acids required for purines?

Answer 6

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

Question 7

Vitamin required for purine synthesis?

Answer 7

tetrahydrofolate (active form of folate)

Question 8

Sources of Carbons in Purines?

Answer 8

Glycine
Tetrahydrofolate
CO2

Question 9

Sources of Nitrogens in Purines?

Answer 9

GlutamiNe

Aspartate

Question 10

Needed to make pyrimidines:

Answer 10

Aspartate
Carbamoyl phosphate (CO2, Glutamine, ATP)

Question 11

Describe chemical structure of CARBAMOYL PHOSPHATE

Answer 11

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)

Question 12

Synthesis of what nucleotide requires ATP?

Answer 12

Pyrimidines

Carbamoyl phosphate has 1 phosphate group that phosphorylates

Question 13

Sources of nitrogen in pyrimidines

Answer 13

glutamine

Question 14

Sources of phosphate in pyrimidines

Answer 14

ATP

Question 15

Sources of carbon in pyrimidines

Answer 15

CO2

Question 16

Drug inhibiting dihydrofolate reductase

Answer 16

Prokaryotes: trimethoprim
Eukaryotes: methotrexate

Question 17

Drug inhibiting thymidylate synthase

Answer 17

5-fluorouracil

Question 18

Drug inhibiting ribonucleotide reductase

Answer 18

Hydroxyurea (sickle cell, cancer)

Question 19

Autosomal recessive disease: deficiency of UMP synthase

Answer 19

Orotic aciduria

No conversion of oritic acid to UMP

Elevated orotic acid in urine
Ammonia blood levels normal

Question 20

Elevated orotic acid + hyperammonemia

Answer 20

Ornithine transcarbamoylase deficiency (OTC deficiency)

Question 21

Elevated orotic acid, with NO hyperammonemia

Answer 21

Orotic aciduria

Question 22

Megaloblastic anemia

Answer 22

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)

Question 23

Treatment for Orotic aciduria

Answer 23

Supplemental dietary uridine

Since UMP synthase is deficient, bypass this step.

Question 24

Drug that inhibits Glutamine PRPP Amidotransferase?

What process is disrupted?

Answer 24

6-mercaptopurine disrupts production of IMP in PURINE SYNTHESIS

Question 25

Drug that inhibits IMP dehydrogenase? | What chemical deficiency results?

Answer 25

``` Mycophenolate GMP synthesis (from IMP) is disrupted ```

Question 26

Purine de novo synthesis RLE?

Answer 26

Glutamine PRPP amidotransferase

Question 27

Pyrimidine synth. RLE?

Answer 27

Carbamoyl phosphate synthase II (CPSII)

Question 28

Drugs METABOLIZED BY xanthine oxidase?

Answer 28

azathioprine 6-mercaptopurine THEREFORE: inhibiting XO results in increased toxicity of THESE DRUGS

Question 29

Drugs inhibiting xanthine oxidase?

Answer 29

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

Question 30

Xanthine oxidase inhibition results in decreased metabolism of these drugs.

Answer 30

azathioprine | 6-mercaptopurine

Question 31

Deficiency of HGPRT

Answer 31

Lesch-Nyhan Syndrome Hypoxanthine, Guanine are NOT recycled to IMP, GMP --> resulting in overproduction of URIC ACID

Question 32

Findings in Lesch-Nyhan Syndrome:

Answer 32

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

Question 33

Treatment of Lesch-Nyhan Syndrome:

Answer 33

allopurinol (treats gout) Cannot treat CNS features.

Question 34

Adenosine deaminase deficiency results in what

Answer 34

SCID

Question 35

What cells are affected in SCID?

Answer 35

T-cells and B-cells

Question 36

Clinical triad of SCID?

Answer 36

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

Question 37

What accounts for negative charge in DNA?

Answer 37

phosphate groups