Nucleotide Metabolism

Question 1

Nucleoside is composed of what 2 things?

Nucleotide is composed of what 2 things?

Answer 1

Nitrogenous base + sugar

Nucleoside + 1-3 phosphate groups

Question 2

What makes ATP/GTP high energy bonds that are able to drive many biochemical reactions

Answer 2

The anhydride bonds linking the 2nd and 3rd phosphate on a nucleoside triphosphate

Question 3

First step in purine nucleotide synthesis

Answer 3

Ribose-5-phosphate gets converted to PRPP by PRPP synthetase

Question 4

Where is the ribose-5-phosphate come from?

Answer 4

HMP shunt (well fed state)

Question 5

1. Activator of PRPP synthetase?

2. Inhibitor?

Answer 5

1. Inorganic phosphate

2. Purine ribonucleotides

Question 6

Where is the pyrophosphate attached?

What else will be attached here?

Answer 6

The first carbon

Nitrogenous base

Question 7

Purine synthesis is the default production of ___; in order to make ___, other steps with be taken

Answer 7

Ribonucleotides; deoxyribonucleotides

Question 8

Rate limiting step of purine nucleotide synthesis

Answer 8

PRPP amidotransferase

Question 9

What is the purpose of folate in purine nucleotide synthesis

Answer 9

Folate is required as a carbon donor

Question 10

What is the form in which folate is used?

What is required to make this form/what does it do

Answer 10

THF (tetrahydrofolate)

Dihydrofolate reductase/ it is the enzyme that converts dihydrofolate to trihydrofolate (THF)

Question 11

1. PRPP amidotransferse is activated by?

2. Inhibited by?

Answer 11

1. PRPP (substrate)

2. Purine nucleotides (end products)(IMP, AMP, and GMP) and 6-mercaptopurine

Question 12

What drug inhibits dihydrofolate reductase?

What type of analog is it?

Only works on what type of cells?

Answer 12

Methotrexate (an anti-tumor drug)

Folic acid analog

Mammalian

Question 13

Sulfonamides:

1. Structural analogs of ?
2. Competitive inhibitor of?
3. Only works in
4. What type of drugs are sulfa drugs

Answer 13

1. PABA (para-aminobenzoic acid)
2. Bacterial purine synthesis/production of folic acid
3. Bacteria (because humans get folate from their diet)
4. Antibiotics

Question 14

1. PYRIMIDINE nucleotide synthesis- what is the rate limiting enzyme
2. Activated by
3. Inhibited by
4. Where in the cell is the enzyme located

Answer 14

1. CPS II (carbamoyl phosphate synthetase II)
2. PRPP
3. UTP (end product)
4. Cytoplasm

Question 15

Which is higher, production of pyramidines or purines?

Answer 15

Production of pyramidines because they are smaller

Question 16

What provides the pentose for pyrimindine needed for synthesis?

Answer 16

PRPP - pyrimidine bases are produced then attached to PRPP

Question 17

Function of ribonucleotide reductase

What drug inhibits this enzyme?

What else does this drug treat? How?

Answer 17

Converts ribonucleotides to deoxyribonucleotides

Hydroxyurea (anti-tumor drug)

Sickle cell anemia; increases the synthesis of fetal hemoglobin

Question 18

Additional steps to convert dUMP to dTMP use which enzyme?

This enzyme is inhibited by?

Answer 18

Thymidylate synthase

5-fluorouracil (5-FU)

Question 19

Hydroxyurea and 5-FU affect production of?

What is significant about this?

Answer 19

Affects the production of DNA but not RNA

Those drugs are good at targeting rapidly dividing cells

Question 20

Thymidylate synthase requires?

Answer 20

Folate in the form of THF

Question 21

What does the drug trimethoprim do?

Answer 21

Antibiotic that inhibits the prokaryotic version of dihydrofolate reductase (eukaryotic version is inhibited by methotrexate)

Question 22

Purine salvage pathway:

Nitrogenous base is recovered after removing phosphate and sugar moieties yielding what 2 things?

Answer 22

Hypoxanthine or guanine

Question 23

1. What is one of the causes severe combined immunodeficiency disease (SCID)
2. What 2 cells are particularly affected by this deficiency
3. What does SCID cause for its patients?
4. Treatment
5. Whats significant about SCID clinically?

Answer 23

1. Adenosine deaminase deficiency
2. T-cells and B-cells
3. Requires them to live in a sterile bubble
4. Bone marrow transplant or enzyme replacement
5. First successful gene therapy trial

Question 24

After recovery of the nitrogenous base in the degradation/salvage pathway, what 2 things can happen to the base?

Answer 24

The base can be shuttled back into purine synthesis or degraded to uric acid

Question 25

Excretion pathway uses which intermediate and which enzyme to produce uric acid?

Answer 25

Intermediate xanthine and the enzyme xanthine oxidase

Question 26

1. What is a result of hyperuricemia?
2. Causes accumulation of?
3. 3 things that under-excretion of uric acid can be caused by?

Answer 26

1. Gout
2. Uric acid crystals in the joints
3. Poor kidney function, acid-base imbalance, and certain drugs (anti-tumor drugs)

Question 27

2 things that cause gout

What body part can gout affect besides joints

Answer 27

Under excretion of uric acid (most common) or overproduction of uric acid

The eye

Question 28

What drug is used if you over produce uric acid? What does it inhibit

Answer 28

Allopurinol - inhibits xanthine oxidase (which produces uric acid)

Question 29

Lesch-Nyhan syndrome

1. Deficiency in?
2. Caused by defect in?
3. Results in extreme, why?
4. Symptoms

Answer 29

1. Purine salvage pathway/purines
2. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
3. Hyperuricemia because purine degradation products are forced into uric acid production since they cannot do pathway
4. Severe mental retardation and self destructive behavior/self-mutilation