Lecture 39 Flashcards Preview

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Flashcards in Lecture 39 Deck (27)
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1

What is a nucleoside?

N-containing base and ribose (no P)

2

what is a nucleotide?

N-containing base, ribose, and phosphate

3

What is the bond between the base and the ribose?

beta-N-glycosidic linkage

4

What are the precursor molecules to make a purine nucleotide?

glutamine, glycine, aspartate and formyl tetrahydrofolate

5

explain the pentose phosphate pathway?

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

6

What is the regulated enzyme in the pentose phosphate pathway?

PRPP

7

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

Phosphoribosylamidotransferase: Committed step
(Regulated step) – N donated by glutamine

8

How is IMP converted into ATP

1. requires GTP

2. IMP + GTP will make AMP

3. AMP + kinase = ADP

4. ADP + kinase = ATP

9

How is IMP converted into GTP

1. requires ATP

2. ATP + GTP = GMP

3. GMP + kinase = GDP

4. GDP + kinase = GTP

10

How is the production of ATP and GTP managed?

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

11

What inhibits the conversion of IMP to GMP?

mycophenolic acid

12

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

PRPP

high PRPP in the cell leads to increased purine synthesis

13

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

Feedback inhibition!

abundant purine nucleotides will inhibit the enzymes PRPP and phosphoribosylamidotransferase

14

How is folate used in purine synthesis? (Humans)

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

15

What drug can be used to inhibit dihydrofolic reducatse?

trimethoprim

anti-microbial

16

What can trimethoprim be used for?

psoriasis

RA

cancer

17

How to inhibit bacterial conversion of PABA to folate?

sulfonamide / sulfa drugs

anti-bacterial

18

methotrexate?

folate analog; competitive inhibitor of dihydrofolate reductase

anti-cancer drug

less purine synthesis

19

thiopurine and azathioprine

anti cancer drugs

20

what occurs during folate deficiency?

macrocytic anemia and decreased cell division

can lead to neural tube defects in a fetus

21

how do ribonucleotides get converted into deoxynucleotides?

ribonucleoside diphosphate is converted to deoxyribonucleoside diphosphate by ribonucleotide reductase

22

what does the enzyme ribonucleotide reductase need?

thioredoxin and NADPH+H

23

What can inhibit the conversion of ribo to deoxyribo?

a lot of dATP

24

what drug can inhibit ribonucleotide reductase?

hydroxyurea

25

What are the enzymes of the purine salvage pathway?

HGPRT and APRT

26

What does the loss of the HGPRT enzyme cause?

lesch-nyhan syndrome

27

symptoms of lesch- nyhan?

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

self-mutilation at the lips and fingers

intellectual disability