Lecture 39

Question 1

What is a nucleoside?

Answer 1

N-containing base and ribose (no P)

Question 2

what is a nucleotide?

Answer 2

N-containing base, ribose, and phosphate

Question 3

What is the bond between the base and the ribose?

Answer 3

beta-N-glycosidic linkage

Question 4

What are the precursor molecules to make a purine nucleotide?

Answer 4

glutamine, glycine, aspartate and formyl tetrahydrofolate

Question 5

explain the pentose phosphate pathway?

Answer 5

1. ribose phosphate
2. PRPP synthetase enzyme
3. Phosphoribosyl pyrophosphate (PRPP)
4. Phosphoribosylamidotransferase with glutamate
5. Phosphoribosylamine
6. Other C and N atoms are added to make Inosine mono phosphate (IMP)
7. IMP can be converted into either AMP or GMP

Question 6

What is the regulated enzyme in the pentose phosphate pathway?

Answer 6

PRPP

Question 7

What enzyme is the committing step in the pentose phosphate pathway?

Answer 7

Phosphoribosylamidotransferase: Committed step

(Regulated step) – N donated by glutamine

Question 8

How is IMP converted into ATP

Answer 8

1. requires GTP
2. IMP + GTP will make AMP
3. AMP + kinase = ADP
4. ADP + kinase = ATP

Question 9

How is IMP converted into GTP

Answer 9

1. requires ATP
2. ATP + GTP = GMP
3. GMP + kinase = GDP
4. GDP + kinase = GTP

Question 10

How is the production of ATP and GTP managed?

Answer 10

They cross regulate each other with ensures that ATP and GTP are the same concentration in the cell

Question 11

What inhibits the conversion of IMP to GMP?

Answer 11

mycophenolic acid

Question 12

What enzyme in the pentose phosphate pathway is a feedforward activator?

Answer 12

PRPP

high PRPP in the cell leads to increased purine synthesis

Question 13

How does an abundance of pruine nucleotides impact the pentose phosphate pathway?

Answer 13

Feedback inhibition!

abundant purine nucleotides will inhibit the enzymes PRPP and phosphoribosylamidotransferase

Question 14

How is folate used in purine synthesis? (Humans)

Answer 14

1. must get folate in the diet
2. folic acid is converted to dihydrofolic acid by dihydrofolate reductase
3. dihydrofolic acid is converted to tetrahydrofolic acid by dihydrofolate reductase
4. THF or tetrahydrofolic acid is used for purine synthesis

Question 15

What drug can be used to inhibit dihydrofolic reducatse?

Answer 15

trimethoprim

anti-microbial

Question 16

What can trimethoprim be used for?

Answer 16

psoriasis

RA

cancer

Question 17

How to inhibit bacterial conversion of PABA to folate?

Answer 17

sulfonamide / sulfa drugs

anti-bacterial

Question 18

methotrexate?

Answer 18

folate analog; competitive inhibitor of dihydrofolate reductase

anti-cancer drug

less purine synthesis

Question 19

thiopurine and azathioprine

Answer 19

anti cancer drugs

Question 20

what occurs during folate deficiency?

Answer 20

macrocytic anemia and decreased cell division

can lead to neural tube defects in a fetus

Question 21

how do ribonucleotides get converted into deoxynucleotides?

Answer 21

ribonucleoside diphosphate is converted to deoxyribonucleoside diphosphate by ribonucleotide reductase

Question 22

what does the enzyme ribonucleotide reductase need?

Answer 22

thioredoxin and NADPH+H

Question 23

What can inhibit the conversion of ribo to deoxyribo?

Answer 23

a lot of dATP

Question 24

what drug can inhibit ribonucleotide reductase?

Answer 24

hydroxyurea

Question 25

What are the enzymes of the purine salvage pathway?

Answer 25

HGPRT and APRT

Question 26

What does the loss of the HGPRT enzyme cause?

Answer 26

lesch-nyhan syndrome

Question 27

symptoms of lesch- nyhan?

Answer 27

serum uric acid is high which results in orange crystals in the diapers

self-mutilation at the lips and fingers

intellectual disability