Nucleotides

Question 1

Purine base production requires

1. 2.
   3.
   4.

Pyrimidine base production requires

1.

Answer 1

THF, glutamine, glycine, aspartate

aspartate

Question 2

PRPP + amino group = _______, which is then converted to either AMP or GMP in purine de novo synthesis

Answer 2

IMP

Question 3

Carbamoyl phosphate is converted to _________ in the pyrimidine base de novo pathway

Answer 3

orotic acid, a temporary pyrimidine base

Question 4

Carbamoyl phosphate is involved in these two metabolic pathways

Answer 4

1. De Novo Pyrimidine Synthesis

2. Urea Cycle

Question 5

OTC enzyme deficiency in the urea cycle leads to the accumulation of _____________ in the mitochondria, which leaks out and is shunted to the pyrimidine de novo pathway, creating high levels of _____________ and _________________

Answer 5

Carbamoyl phosphate

Orotic acid and ammonia (no urea cycle)

Question 6

5-FU inhibits this enzyme in de novo pyrimidine synthesis

Answer 6

Thymidylate Synthase

Question 7

Orotic acid is converted to _______ , which is converted to UDP in the de novo pyrimdine pathway

Answer 7

UMP

Question 8

UDP is converted to dUDP by this enzyme, which requires NADPH in the de novo pyrimdine pathway

Answer 8

Ribonucleotide Reductase

Question 9

Hydroxyurea blocks this enzyme in the de novo pyrimdine pathway

Answer 9

Ribonucleotide Reductase

Question 10

dUDP is converted to dUMP, which is then converted to dTMP

Answer 10

Thymidylate Synthase

Question 11

5-FU blocks this enzyme in the de novo pyrimdine pathway

Answer 11

Thymidylate Synthase

Question 12

These three drugs block DHFR, which converts DHF to THF (N-5, N-10), which is cofactor for thymidylate synthase

Answer 12

1. MTX
2. TMP
3. Pyrimethamine

Question 13

Inability to convert orotic acid to UMP because of a defect in _______________ causes orotic aciduria

Answer 13

UMP synthase

Autosomal recessive

Question 14

This disease causes megaloblastic anemia that does not improve with administration of B-12 or folic acid, failure to thrive, and increased orotic acid in urine

Answer 14

Orotic aciduria, defect in UMP Synthase in de novo pyrimidine pathway

NO HYPERAMMONIA (vs OTC deficiency)

Question 15

Treat orotic aciduria with ____________

Answer 15

Oral uridine administration to maintain nucleotide synthesis

Question 16

Unlike purine degradation products, pyrimidine degradation products are _______________

Answer 16

soluble

Question 17

B-aminoisobutyrate levels, which are a byproduct of _____________ are often used in urinanaysis as ain indication of _______________

Answer 17

Pyrimidine turnover

DNA turnover

Question 18

Those taking allopurinol (often used to prevent gout) are at risk for ____________ toxicity. The dose should be reduced or allopurinol should be discontinued.

Answer 18

6-MP - is normally metabolized by xanthine oxidase

Question 19

In adenosine deaminase deficiency, there is excess _________, which feedback inhibits ____________, preventing DNA synthesis and manifesting in SCID.

Answer 19

ATP and dATP
Ribonucleotide Reductase (feedback inhibited by all purines - AMP, IMP, GMP

Question 20

In Lesch-Nyhan Syndrome, there is absence of ______, which converts hypoxanthine to ________ and guanine into _________. Without the production of these in the salvage pathway, the ____________ enzyme is not under negative feedback, resulting in greater flux through the de novo pathway –> gout.

Answer 20

HGPRT
IMP
GMP
PRPP Synthetase