13: Nucleotide Metabolism

Question 1

Purine vs pyrimidine rings

Answer 1

Purine: 2 rings
Pyrimidine: 1 ring

Question 2

Nucleoside vs nucleotide parts

Answer 2

Nucleoside: N base + sugar
Nucleotide: N base + sugar + phosphate

Question 3

Two places where nucleosides play roles

Answer 3

Adenosine, vitamin B12

Question 4

De novo synthesis of pyrimidines vs purines

Answer 4

Pyrimidines: form ring structure then add PRPP
Purines: form PRPP and form the rings on top of that

Question 5

Salvage pathway of purines

Answer 5

Adding R5P to the pre-formed purine base

Question 6

Salvage pathway of pyrimidines

Answer 6

Forming pyrimidines from pyrimidine bases in RNA/DNA

Question 7

Site for de novo synthesis vs salvage pathways

Answer 7

De novo: cytosol (+mito for pyrimidines)

Salvage: organelles

Question 8

What organ does de novo synthesis take place in?

Answer 8

Liver

Question 9

What is notable about all intermediates of purine de novo synthesis

Answer 9

All intermediates are phosphorylated due to phosphate group on R5P

Question 10

Carbon sources for purine de novo synthesis

Answer 10

1. 2C from folate
2. 1C from CO2
3. Rest of Cs: Gln, Gly, Asp

Question 11

Major regulatory process in purine de novo synthesis and which four enzymes it affects

Answer 11

Feedback inhibition

1. PRPP synthetase
2. Phosphoribosyl pyrophosphate aminotransferase
3. Adenylosuccinate synthase
4. IMP dehydrogenase

Question 12

What does elevated carbamoyl phosphate cause?

Answer 12

Hyperammonemia with orotic acid

Question 13

What are the major branching points in pyrimidine and purine synthesis?

Answer 13

Purine: IMP
Pyrimidine: UMP

Question 14

dUMP loop purpose

Answer 14

Is wasteful, but occurs so that dUTPase keeps dUTP low to prevent incorporation into DNA

Question 15

Organs where PPP takes place

Answer 15

RBCs, liver, testes, mammary glands, adrenal cortex

Question 16

Oxidation of purines during de novo synthesis

Answer 16

Oxygen is added to molecules as the pathway progresses, making them more and more polar

Question 17

Four molecules in the purine de novo synthesis pathway that exhibit oxidation levels increasing

Answer 17

1. Adenosine = 0 Oxygen
2. Guanine / hypoxanthine = 1 oxygen
3. Xanthine = 2 oxygen
4. Uric acid = 3 oxygen

Question 18

Primary vs secondary hyperuricemia

Answer 18

Primary: overproduction of uric acid
Secondary: underexcretion of uric acid

Question 19

Why does gout occur in more distal joints?

Answer 19

Decreased temp in extremities = decreased uric acid solubility

Question 20

What does overproduction of ADA (adenosine deaminase) cause?

Answer 20

Hemolytic anemia

Question 21

Which is more dominant for purines, de novo synthesis or salvage pathway?

Answer 21

Salvage pathway

Question 22

Purine salvage pathway: enzyme that generates AMP

Answer 22

APRT (adenosine phosphoribosyltransferase

Question 23

Purine salvage pathway: generates GMP or IMP

Answer 23

HGPRT (hypoxanthine-guanine phosphoribosyltransferase)

Question 24

What is Lesch-Nyhan Syndrome called when there is 8%+ of HGPRT still function + the symptoms

Answer 24

Kelley-Seegmiller syndrome - no neurologic symptoms, gout, kidney