Nucleotide Metabolism

Question 1

What are DNA and RNA made from?

Answer 1

Nucleotides

Question 2

What roles do nucleotides play?

Answer 2

• Carriers of activated intermediates in synthesis of carbs, lipids and conjugated proteins
• Structural components of several essential coenzymes (CoA, FAD, NAD + NADP, UDP-glucose)
• Second messengers (cAMP, cGMP)
• Energy currency (ATP)
• Regulatory compounds (ATP when E high, AMP when E low)

Question 3

Why do we need to get nucleotides de novo or through salvage pathways?

Answer 3

We eat a ton of nucleotides but we don’t absorb them -> intestines eliminate them

Question 4

What are the purines?

Answer 4

Adenine and guanine

-2 rings

Question 5

What are the pyrimidines?

Answer 5

Thymine, cytosine, and uracil (RNA)

-1 ring

Question 6

What are nucleosides?

Answer 6

Pentose sugar (from PPP) + base (through glycosidic bond)

Question 7

What are nucleotides?

Answer 7

1 or more phosphate group + nucleoside

• Named by # of phosphates (adenosine monophosphate = AMP, adenosine diphosphate = ADP…)
• Phosphates have high-energy bonds

Question 8

What is the nucleoside of base adenine?

Answer 8

Adenosine

Question 9

What is the nucleoside of base guanine?

Answer 9

Guanosine

Question 10

What is the nucleoside of base cytosine?

Answer 10

Cytidine

Question 11

What is the nucleoside of base thymine?

Answer 11

Thymidine

Question 12

What is the nucleoside of base uracil?

Answer 12

Uridine

Question 13

What is the nucleoside of base hypoxanthine?

Answer 13

Inosine

Question 14

What is purine made from?

Answer 14

3 AAs (Aspartate, Glycine and Glutamine) + CO2 + N-Formyl Tetrahydrofolate (FH4)

Question 15

What happens first in the making of a purine?

Answer 15

Activate Ribose 5-phosphate by PRPP Synthetase using ATP -> PRPP
-Regulated step, but NOT committed

Question 16

What is the committed step in the making of a purine?

Answer 16

PRPP reacts w/ glutamine to form phosphoribosylamine -> nitrogen 9 of purine ring

• Catalyzed by glutamine phosphoribosyl amidotransferase
• Uses H2O and Glutamine -> Glutamate

Question 17

What is the first final purine product?

Answer 17

IMP (contains the base hypoxanthine joined to sugar)

-From here we either make Adenine or Guanine (purines)

Question 18

What does the drug Methotrexate do?

Answer 18

Blocks the use of tetrahydrofolate -> limits purine synthesis -> blocks DNA replication

• Useful in treating cancer but is not specific to just cancer cells
• Ex. of folic acid analog

Question 19

How are the majority of dietary nuclei acids degraded in the small intestine?

Answer 19

Converted to uric acid in intestinal mucosal cells -> blood -> urine

Question 20

Are dietary bases used for synthesis of tissue nucleic acids?

Answer 20

No, but the small intestine can use a small amount of it for its own need (regeneration of intestinal lining) -> the rest converted to uric acid

Question 21

What is gout?

Answer 21

Disorder of hyperuricemia w/ recurrent attacks of acute arthritis joint inflammation, caused by deposition of mono-sodium urate crystals

Question 22

What does gout result from?

Answer 22

Under excretion of uric acid

Question 23

What enzyme is important in the conversion of purines to uric acid?

Answer 23

Xanthine oxidase

Question 24

What is used to treat acute attacks of gout?

Answer 24

Anti-inflammatory agents (colchicine, steroidal drugs-prednisone, non-steroidal drugs-indomethacin)

Question 25

What is used for long-term therapeutic strategies for gout?

Answer 25

Allopurinol - structural analog of hypoxanthine | -Inhibits xanthine oxidase -> reduces uric acid production

Question 26

What is required for an official diagnosis of gout?

Answer 26

Arthrocentesis of joint fluid | -Helps define causes of joint swelling/arthritis (infection, gout, rheumatoid disease)

Question 27

What do you require for the making of a pyrimidine?

Answer 27

CO2 + Glutamine + Aspartate

Question 28

What is the main difference between making a pyrimidine and making a purine?

Answer 28

In making pyrimidine you make the base alone and then you add it to a sugar -In purine you start by activating the sugar and adding to it

Question 29

What is the regulated step in the making of a pyrimidine?

Answer 29

Glutamine + CO2 -> Carbamoyl phosphate | -Catalyzed by carbamoyl phosphate synthetase (CPS) II

Question 30

What are the differences of CPS II and CPS I?

Answer 30

- CPS I: in mitochondria, in urea cycle, FIXES free ammonia | - CPS II: in cytosol, in pyrimidine synthesis, N from gamma-amide group of glutamine (NOT FREE AMMONIA)

Question 31

What is essential for making of DNA and development of neural tube in fetus?

Answer 31

When you make UMP to make TMP for DNA synthesis, difference between U and T is methyl Group, donated by tetrahydrofolate

Question 32

What are 3 carbons in our body specialized in transferring?

Answer 32

Tetrahydrofolate, Vitamin B12 & S-AM (adenosyl methionine)

Question 33

What causes neural tube defects?

Answer 33

In pregnant woman the need for tetrahydrofolate is increased because greater need to make this as fetus grows -Inhibition of dUMP to dTMP -> neural tube defect

Question 34

What is 5-fluorouracil?

Answer 34

Chemotherapy medication | -Inhibits dUMP to dTMP -> stops DNA replication