Nucleotide Metabolism

Question 1

Nucleotide functions

Answer 1

1. Structural component of DNA AND RNA
2. Carriers of activated intermediates (UDP-glucose)
3. Structural components of coenzymes used in metabolism
4. Secondary messengers in signal transduction (cAMP)
5. Energy (ATP)
6. Regulate pathways (using energy)

Question 2

Structure of nucleotides

Answer 2

Nitrogenous base

Sugar

Question 3

Purines

Answer 3

• dicyclic

- adenine and guanine

Question 4

Pyrimidines

Answer 4

• monocyclic

- cytosine, thymine(DNA) and uracil(RNA)

Question 5

Sugar is nucleotides

Answer 5

RNA:ribose
DNA: deoxyribose

Question 6

Why is DNA more stab,e than RNA?

Answer 6

DAN uses deoxyribose which lacks an oxygen so it is more stable

Question 7

Difference between nucleotides and nucleoside

Answer 7

Nucleoside: nitrogenous base and sugar
Nucleotides: nucleoside plus a phosphate group

Question 8

What provides the energy to drive these reaction So?

Answer 8

• anhydride bond links 2 and 3 phosphate on nucleotides
• high energy bond that drives biochemical reactions
• ATP AND GTP

Question 9

Where does the ribose 5p come from for purine synthesis?

Answer 9

HMP shunt

Question 10

What is a key difference in purine and pyramides metabolism?

Answer 10

Purines directly build the nitrogenous base ONTO the sugar

-pyramides build the base then attach it to the sugar

Question 11

PRPP synthase in purine metabolism

Answer 11

• catalyze so formation of the activated pentose

- uses energy

Question 12

Regulation of PRPP SYNTHASE

Answer 12

Activator: inorganic phosphate
Inhibitor: purine ribonucleotides

Question 13

What is the default of purine nucleotides synthesis?

Answer 13

-produces ribonucleotides(not deoxyribose

Question 14

What is the rate limiting step of purine synthesis?

Answer 14

PRPP amidotransferase

Question 15

PRPP AMIDOTRANSFERASE REGULATION

Answer 15

Activated: PRPP (substrate)
Inhibitors: purine nucleotides(end products)

Question 16

What does folate do?

Answer 16

• required for subsequent steps as a carbon donor

- active form is THF

Question 17

What enzyme makes THF

Answer 17

-dihydrofolate reductase turns folate into THF

Question 18

Who makes their own folate?

Answer 18

-bacteria make their own folate, we cant.

Question 19

What does THF turn into?

Answer 19

• THF acts as a carbon donor and makes IMP

- IMP can then turn into AMP and GMP

Question 20

6-Mercaptopurine

Answer 20

• purine analog that acts as a product inhibitor
• inhibits PRPP amidotransferase
• if base is formed, it will have mutations

Question 21

Methotrexate

Answer 21

• folic acid analog
• inhibits digydrofolate reductase so no THF can be made
• works ONLY IN MAMMALS
• selectively inhibits rapidly dividing cells

Question 22

Sulfonamides

Answer 22

• structural analog of para-aminobenzoic acid (PABA)
• competitive inhibitor of bacteria producing folic acid
• bacteria purine synthesis inhibited

Question 23

What is the rate limiting enzyme for pyrimidine synthesis?

Answer 23

-CPS II

Question 24

Regulators of CPS II

Answer 24

• activated by PRPP

- Inhibited by UTP(end product)

Question 25

What are the two amino acids used in nitrogenous base structure of pyrimidines?

Answer 25

-glutamine and aspartate

Question 26

What does PRPP provide for pyrimidine synthesis?

Answer 26

-pentose

Question 27

ribonucleotide reductase

Answer 27

- ribonucleotides are converted into deoxyribonucleotides | - hydroxyurea inhibits it

Question 28

Hydroxyurea

Answer 28

- inhibits ribonucleotide reductase | - also treats sickle cell by promoting fetal hemoglobin

Question 29

convert dUMP into dTMP

Answer 29

-use thymidylate synthase

Question 30

5-FU

Answer 30

-anti tumor drug that inhibits thymidylate synthase

Question 31

what do 5-FU and hydroxyurea target?

Answer 31

- affect production of DNA, but not RNA | - so really good at targeting rapidly dividing cells

Question 32

Trimethoprim

Answer 32

-antibiotic that is selective for the prokaryotic version of dihydrofolate reductase

Question 33

Pyrimidine breakdown

Answer 33

- they are not salvaged to a significant degree | - no high yield disease from breakdown so not important

Question 34

Why is it important to recycle purines?

Answer 34

- purine bases are more complex than pyrimimdines - take more steps to make it - salvaging it is more important because it takes too much energy to make them

Question 35

salvage pathway of purine general

Answer 35

- base is recovered by removing phosphate and sugar moieties - this yields hypoxanthine or guanine - those are shuttled back into synthesis

Question 36

adenosine deaminase deficiency

Answer 36

- causes SCID - immune system(T and B cells) are primarily affected - patients are super susceptible to inflection (bubble) - it cannot be recycled, so youre excreting too much

Question 37

treatment of SCID

Answer 37

-bone marrow transplant or enzyme replacement

Question 38

Xanthine oxidase

Answer 38

- excretion pathway of purines | - produces uric acid which is then excreted as urine

Question 39

Gout

Answer 39

- result of hyperuricemia - accummulation of uric acid crystals in the joints - gouty arthritis

Question 40

What causes gout?

Answer 40

- overproduction of uric acid | - problem with excretion

Question 41

Allopurinol

Answer 41

- inhibits xanthine oxidase | - helps overproducers of uric acid stop making it

Question 42

Lesch-Nyhan syndrome

Answer 42

- X linked - deficiency in purine salvage pathway - defect in HGPRT - you end up excreting like 90% - extreme hyperuricemia

Question 43

Gout and eyeballs

Answer 43

- deposits of tophi in cornea, iris, sclera, lens - formation of transparent vesicles(metalic) - bleeding in subjunctiva