Purine Metabolism

Question 1

Hypoxathine

Answer 1

Base found in inosine monophosphate, and intermediate in purine synthesis and degradation

Question 2

Xanthine

Answer 2

Found in xanthosine MP, an intermediate in purine synthesis

Question 3

Nucleoside

Answer 3

Nitrogenous base+pentose sugar

Question 4

Nucleotide

Answer 4

Nucleoside+phosphate groups

Question 5

In humans, where are the enzymes necessary for de novo purine synthesis found?

Answer 5

The cytoplasm

Question 6

De novo Purine Synthesis

Answer 6

Adding carbon and nitrogen to a preformed ribose-5-phosphate

Question 7

Where do you get the ribose for purine synthesis?

Answer 7

The HMP pathway gives you the ribose-5-phosphate

Question 8

What amino acids donate the nitrogens for purine synthesis?

Answer 8

Glycine, glutamine, and aspartate.

Question 9

What donates the carbon needed for purine synthesis?

Answer 9

Tetrahydrofolate (THF)

Question 10

PRPP

Answer 10

5-phosphoribosyl-1-pyrophosphate. Involved in the synthesis of purines, pyrimidines, and their degradation.

Question 11

What is the rate limiting/committed step for de novo purine synthesis?

Answer 11

PRPP being helping to create 5’-phosphoribosylamine.

Question 12

What controls the first step in de novo purine synthesis?

Answer 12

Concentrations of glutamine and PRPP

Question 13

What is the first nucleotide made in de novo purine synthesis?

Answer 13

IMP

Question 14

Why do sulfa drugs not interfere with human purine synthesis?

Answer 14

Humans can’t synthesize folic acid. (Sulfa drugs affect the synthesis of folic acid in bacteria). They are competitive inhibitors.

Question 15

How does methotrexate work?

Answer 15

Inhibit the synthesis of THF, which slows DNA replication (not enough purines available). Helps treat cancer. Competitively inhibits the enzyme dihydrofolate reductase. It is a structural analog of folic acid.

Question 16

Trimethoprim

Answer 16

Inhibits THF synthesis via dihydrofolate reductase in prokaryotes only

Question 17

Megablastic Anemias

Answer 17

First sign of a folate deficiency. Hemoglobin levels are low and bone marrow shows abnormally high number of megaloblastic cells.

Question 18

Sulfonamides

Answer 18

PABA analogues that inhibit the synthesis of folate in bacteria.

Question 19

What do you need to synthesize AMP from IMP?

Answer 19

GTP and adenylosuccinate synthetase

Question 20

What do you need to convert IMP to GMP?

Answer 20

ATP and GMP synthetase

Question 21

Mycophenolic Acid

Answer 21

Inhibits inosine monophosphate dehydrogenase. Anti-rejection drug as it stops B and T cells from proliferating.

Question 22

Purine salvage: What two enzymes are involved?

Answer 22

HGPRT and APRT

Question 23

Lesch-Nyhan Syndrome and the salvage pathway

Answer 23

LN is caused by a deficiency of HGPRT, meaning it can’t salvage hypoxanthine or guanine, leading to an increase of uric acid.

Question 24

What was HGPRT do?

Answer 24

Converts hypoxanthine to IMP and guanine to GMP

Question 25

What does APRT do?

Answer 25

Convert adenine to AMP

Question 26

what is characteristic of Lesch-Nyhan in babies?

Answer 26

Orange crystals in diaper due to excess uric acid.

Question 27

What are purines degraded to?

Answer 27

Uric acid

Question 28

What happens to ribose and deoxyribose during purine degradation?

Answer 28

They are absorbed into the intestinal mucosa and returned to the circulation

Question 29

ADA and SCIDS

Answer 29

Adenosine deaminase deficiency. Without ADA you cannot turn adenosine into inosine, leading to a buildup of dATP which stops DNA synthesis in T and B cells.

Question 30

PNP Deficiency

Answer 30

Purine nucleoside phosphorylase deficiency causes impairment of T-cell function. Decrease uric acid production and increase in purine production.

Question 31

Colchicine

Answer 31

Microtubule inhibitor that inhibits migration of white cells to joins where uric acid crystals are phagocytized.

Question 32

Allopurinol

Answer 32

Treatment of gout. Non-competitive inhibitor of xanthine oxidase. Causes excretion of hypoxanthine and xanthine instead of urate.

Question 33

Where do you get the carbons for pyrimidine synthesis?

Answer 33

Aspartic acid

Question 34

Where do you get the nitrogen for pyrimidine synthesis?

Answer 34

Glutamine

Question 35

What is the rate limiting step for pyrimidine synthesis?

Answer 35

Synthesis of carbamoyl phosphate from glutamine and CO2 CPS II

Question 36

Carbamoyl Phosphate Synthetase II

Answer 36

CPS II. Involved in pyrimidine synthesis. Used glutamine as the source of nitrogen. Occurs in the cytoplasm of all nucleated cells. Inhibited by UDP and UTP.

Question 37

Orotic Aciduria

Answer 37

Causes abnormal growth, megaloblastic anemia, and excretion of large amounts of orotic acid in urine. Caused by a deficiency in orotate phosphoribosyltransferase and OMP.

Question 38

Synthesis of CTP from UTP

Answer 38

UMP–>UDP–>UTP (by kinases)—>CTP by CTP synthase

Question 39

Ribonuelctoide Diphosphate Reductase

Answer 39

Enzyme that catalyzes the reaction of ribonuelceotides to deoxyribonucleotides

Question 40

What inhibits ribonuelceotide Diphosphate reductase?

Answer 40

dATP and hydroxyurea

Question 41

Synthesis of thymidine MP

Answer 41

Thymidylate synthase uses THF to produce dTMP from dUMP

Question 42

5-Fluorouracil

Answer 42

Uracil analog. Anti-cancer drug that blocks dTMP production.