Pyrimidines

Question 1

substrates needed for synthesis of pyrimidine

Answer 1

glutamine, aspartic acid, and CO2 (NO FOLIC ACID!!!!)

Question 2

rate limiting step of pyrimidine synthesis

Answer 2

CPS II

Question 3

inhibitor of CPS II

Answer 3

its products UDP or UTP

Question 4

activator of CPS II

Answer 4

ATP and PRPP

Question 5

characteristics of CPS I

Answer 5

involved in urea synthesis, uses free NH3, happens in liver mito, activated by NAG, not affected by UDP or UTP

Question 6

characteristics of CPS II

Answer 6

involved in pyrimidine synthesis, use Gln, happens in cytosol, inhibited by UDP or UTP, not affected by NAG

Question 7

Orotic Aciduria occurs because of …?

Answer 7

deficiency in orotate phosphoribosyltransferase and OMP decarboxylase

or as a result of OTC deficiency

Question 8

difference between orotic acidura caused by OTC deficiency or one caused by deficiency of OMP decarboxylase and orotate phosphoribosyltransferase

Answer 8

orotic acidura with OTC deficiency also presents with hyperammonemia

and with the other two deficiency it is just orotic aciduria

Question 9

what does orotic aciduria cause

Answer 9

abnormal growth, megaloblastic anemia, excretion of orotic acid in urine

Question 10

treatment for orotic aciduria

Answer 10

with dietary uridine

Question 11

name the enzymes in each step: UMP –> UDP–>UTP

Answer 11

nucleoside monophosphate kinase and

nucleoside diphosphate kinase

Question 12

UTP is converted to CTP using what

Answer 12

CTP synthase and glutamine

Question 13

enzyme going from ribonucleoside diphosphate to deoxyribonucleoside diphosphate

ADP –> dADP
UDP –>dUDP
GDP –> dGDP

Answer 13

ribonucleotide diphosphate reductase

Question 14

inhibitor of ribonucleotide diphosphate reductase

Answer 14

dATP and hydroxyurea

Question 15

what occurs at the two activity sites of ribonucleotide diphosphate reductase

Answer 15

bind dATP which decreases activity (explains high dATP in ADA deficiency)

or can bind ATP which increases activity

Question 16

how do you maintain balance of DNA synthesis

Answer 16

bind an NTP which causes an increase in conversion of ribonucleotide to deoxynucleotide

Question 17

dUMP –> dTMP using what?

Answer 17

Thymidylate synthase and THF

Question 18

dUMP –> dTMP can be indirectly inhibited by?

Answer 18

MTX

Question 19

what drug can inhibit thymidylate synthase

Answer 19

5-fluorouracil

Question 20

what inhibits THF

Answer 20

methotrexate

Question 21

Drugs that can be used to treat cancer

Answer 21

methotrexate, 5 fluorouracil, AraC

remember if you can inhibit one of the nucleotides for synthesizing DNA, you completely stop the synthesis

Question 22

NOT A QUESTION but something impo about pyrimidines

Answer 22

pyrimidines unlike purines can be degraded into highly soluble structures that can be used for other biomolecules

Question 23

what salvages pyrimidine

Answer 23

pyrimidine phosphoribosyltransferase -

Question 24

what is the source of ribose phosphate when pyrimidine is being salvaged

Answer 24

PRPP

Question 25

CLICKER QUESTIONS: committed step of purine nucleotide synthesis is the formation of?

Answer 25

phosphoribosylamine

Question 26

CLICKER QUESTION: A 2 year old infant has orotic aciduria and megaloblastic anemia. what would improve her anemia?

Answer 26

uridine