Molecular Biology

Question 1

Name the drugs that cause drug induced lupus

Answer 1

Isoniazid (tb drug)
Hydrolazine (vasondilatador for high blood pressure)
Procainamid (anti arritmic)

Question 2

What’s an histone

Answer 2

DNA protein (H1; H2A; H2B; H3; H4)
H1 keeps them together : the rest binds and form octameter (8 histones)

Question 3

What causes drug induced lupus?

Answer 3

Anti histones antibodies

Question 4

Which aa gives Nitrogen to Purines?

Answer 4

Glutamine (2 N)
Aspartate ( 1N to the 6th ring)
Glycine (carbons and N)

Question 5

What are the carbon sources of Purines?

Answer 5

CO2 (1 in 6C ring)
Tetrahydrofolate (2; 1 to each ring)
Glycine (2; each ring)

Question 6

Drugs that inhibit IMP dehydrogenase

Answer 6

Ribavirin
Mycophenolate

Question 7

Antiviral that blocks conversion of IMP to GMP

Answer 7

Rivabirin,
Inhibits guanine nucleotides

Question 8

Immunosuppressant that inhibits IMP dehydrogenase in white cells

Answer 8

Mycophenolate

Question 9

Chemotherapy agent that mimics hypoxantine/ guanine to inhibit the novo synthesis

Answer 9

Azathioprine -> 6-mercaptopurine [6-mp])
Creates thioniosinic acid
(Decreases DNA synthesis by decreasing IMP/GMP/AMP)

Question 10

Enzyme deficient or disfunctional in the severe combined immunodeficiency syndrome

Answer 10

Adenosine deaminase
(Purine -Adenine- breakdown pathway)

Question 11

Inhibits xanthine oxidase

Answer 11

Allopurinol
(Tx for gout )

Question 12

Lesch Nyhan syndrome

Answer 12

X linked deficiency of HGPRT

Question 13

Excess De Novo synthesis (PRPP -IMP)

Answer 13

Lesch nyhan syndrome

Question 14

Source of C an N of pyrimidine rings

Answer 14

Carbamoil Phospate - 1 C and 1 N
Aspartate - 3 C and 1 N

Question 15

Defect in UMP synthase

Answer 15

Orotic aciduria

Question 16

Synthesis of pyrimidine bases

Answer 16

Glutamine -> catbamoil phosphate -> Orotic acid ——-—->UMP -> CMP - TMP
———————————————————————UMP synthase

Question 17

Orotic Aciduria
(5 characteristics)

Answer 17

• Autosomal Recessive
• loss of pyrimidines
• Orotic acid in urine
• megaloblastic anemia (folate deficiency) that does NOT respond to folate treatment
• grow retardation

Question 18

Treatment for Orotic aciduria

Answer 18

Uridine (bc bypasses the UMP synthase)

Question 19

Ornithine transcarbamylase (OTC) deficiency

Answer 19

X-linked
Increases carbamoyl phosphate -> high Orotic acid -> Orotic aciduria
High amonia levels

Question 20

Differences between OTC deficiency and Orotic Aciduria

Answer 20

In OTC deficiency: - high Orotic acid levels both urine and plasma
- high ammonia (due to impaired urea synthesis)
-Encephalopathy

Orotic aciduria :- megaloblastic anemia non responding to folate
- high Orotic acid levels both plasma and urine

Question 21

Chemotherapy agent Ara-C (cytarabine) Mechanism of action

Answer 21

Mimics dCTP (pyrimidine analog)
Inhibits DNA polymerase

Question 22

Hydroxyurea mechanism of action

Answer 22

Inhibits ribonucleotide reductase

(Causes increased fetal hemoglobin by unclear mechanism )

Question 23

Uses of hydroxyurea

Answer 23

• polycythemia Vera; essential thrombocytosis -> blocks formation of deoxynucleotides
  -sickle cell anemia(increase hbF)

Question 24

How folate regulates the conversion of dUMP to dTMP

Answer 24

By giving 1 C through the enzyme thymidylate synthase; the C comes from N5; N10 tetrahydrofolate

[folate -> dehydrofolate -> Tetrahydrofolate -> N5 N10 tetrahydrofolate]

Question 25

Chemotherapy agent that inhibits thymidylate synthase and blocks dTMP

Answer 25

5-FU(floururacil) (Cancer cells can’t synthesize thymine so they die)

Question 26

Side effect of methotrexate use

Answer 26

Bone marrow suppression Can be rescue with Leucovorin (folinic acid converted into Tetrahydrofolate)

Question 27

Immunosuppressant that inhibits dihydrofolate reductase

Answer 27

Methotrexate (Dihydrofolate reductase converts dihytrofolate to Tetrahydrofolate and Tetrahydrofolate is needed to convert dUMP to dTMP)

Question 28

Antibiotics that blocks (bacterial DNA )Tetrahydrofolate synthesis

Answer 28

Sulfonamides -> inhibits dihydropteroate synthase Trimethoprim -> inhibits dihydrofolate reductase (the bacterial one)

Question 29

What’s required to generate THF from N5 Methyl THF

Answer 29

Vitamin B12

Question 30

Difference between folate and b12 deficiency

Answer 30

Fiolate: megaloblastic anemia ; no neurological impairment B12= demyelination . (Can overcome /b12 deficiency with high folate intake)

Question 31

How to tell apart a B12 vs a B9 deficiency

Answer 31

In both homocysteine levels will be high (bc you need them both to convert homocysteine to methionine) In B12 deficiency methymalonic, MMA, acid levels will be high ( bc you need B12 to convert MMA to succinyl coA)

Question 32

Drug induced Megaloblastic anemia

Answer 32

- Methotrexate - 5-Floururacil - hydroxyurea

Question 33

II; VII; IX;X

Answer 33

For vitamin K