Biochem

Question 1

What amino acids are necessary for purine synthesis?

Answer 1

Glycine (carbon)
Aspartate (nitrogen)
Glutamine (nitrogen)

(also need CO2 and THF)

Question 2

What is the rate limiting step of purine synthesis?

Answer 2

Glutamine PRPP amidotransferase

Question 3

What drugs inhibit glutamine PRPP amidotransferase?

Answer 3

6-mercaptopurine

Azathioprine (6-MP prodrug)

Question 4

What type of drug is azathioprine?

Answer 4

Azathioprine is an immunosuppressant

Question 5

What are some possible toxicities of azathioprine?

Answer 5

Leukopenia
Anemia
Thrombocytopenia

Question 6

What enzyme degrades 6-MP?

Answer 6

Xanthine oxidase…allopurinol inhibits this enzyme…FYI

Question 7

When is 6-MP used?

Answer 7

Leukemia

IBD

Question 8

What is needed for pyrimidine synthesis?

Answer 8

Aspartate
Carbamoyl phosphate
THF

Question 9

What is the rate limiting step of pyrimidine synthesis?

Answer 9

Carbamoyl Phosphate Synthetase II (CPS 2)

Requires ATP

Question 10

UMP synthase is another necessary enzyme in pyrimidine synthesis. What happens when this enzyme is deficient?

Answer 10

Orotic Aciduria

Question 11

What are the signs of orotic acuduria?

Answer 11

Increased orotic acid in urine
Normal urine ammonia level
Megaloblastic anemia that is NOT cured with folate/B12

Question 12

Ribonucleotide reductase is the enzyme that puts the d in dna. What drug inhibits this enzyme?

Answer 12

Hydroxyurea

Question 13

When is hydroxyurea used?

Answer 13

CML
Skin cancer
Sickle cell disease (increases HbF)

Question 14

What are the side effects of hydroxyurea?

Answer 14

Bone marrow suppression

GI upset

Question 15

What drug inhibits the methylation of dUMP to dTMP?

Answer 15

5-Fluorouricil (5-FU)

Flucytosine gets converted to 5-FU

Question 16

When is 5-FU used?

Answer 16

Colon cancer
Pancreatic cancer
Basal cell carcinoma

Question 17

What are the side effects of 5-FU?

Answer 17

Myelosupression

Photosensitivity

Question 18

When is flucytosine used?

Answer 18

Systemic fungal infections…given with amphotericin B

Question 19

DHFR is also necessary for the methylation of dUMP. What drugs inhibit DHFR?

Answer 19

Methotrexate (humans)
Trimethoprim (bacteria)
Pyrimethamine (protozoa)

Question 20

What enzyme is necessary for the conversion of adenosine to inosine (for the purine salvage pathway)?

Answer 20

Adenosine deaminase (ADA)

Question 21

What is the metabolic effect of ADA deficiency?

Answer 21

A build up of ATP and dATP causes a feedback inhibition on ribonucleotide reductase…NO DNA synthesis

Question 22

What is the medicinal effect of ADA deficiency?

Answer 22

SCID (No B cells or T cells)
Chronic diarrhea
FTT
No thymic shadow on CXR

Question 23

Lesch-Nyhan syndrome is a purine salvage disease. What enzyme is deficient with this disease?

Answer 23

HGPRT

Question 24

What are the s/s of Lesch-Nyhan syndrome?

Answer 24

"HGPRT"
H- Hyperuricemia
G- Gout
P- Pissed off (aggression, self-mutilation)
R- Retardation (intellectual disability)
T- dysTonia

Question 25

What cancer gene includes a MMR mutation?

Answer 25

HNPCC

Question 26

What is an effect of mutated NER?

Answer 26

Xeroderma pigmentosa | easy to remember because UV rays cause thymine dimers...and NER fixes thymine dimers

Question 27

What syndrome is caused by a helicase mutation?

Answer 27

Bloom syndrome

Question 28

What process is mutated with ataxia telangiectasia?

Answer 28

NHEJ

Question 29

BRCA1&2 are mutations in what process?

Answer 29

dsDNA break repair