Nucleic Acid Metabolism - Biochem

Question 1

In the IMP biosynthesis pathway, where does PRPP come from and what is the final product?

Answer 1

Ribose-5-P and ATP

IMP

Question 2

What are the major key regulatory steps in the IMP biosynthesis pathway?

Answer 2

Inhibitors: NTP, NDP, NMP
activators: PRPP

Question 3

What is Inosinate (IMP) a derivative of?

Answer 3

Adenylate (AMP), Guanylate (GMP)

Question 4

What is added to IMP to create adenylosuccinate?

Answer 4

aspartate, GTP, adenylosuccinate synthetase

Question 5

What is added to adenylosuccinate to create adenylate (AMP), and what is removed?

Answer 5

adenylosuccinate lyase

fumarate is removed

Question 6

What is added to IMP to make XMP?

Answer 6

H20, NAD+

Question 7

What is added to XMP to create GMP? WHat is removed?

Answer 7

Gln, and ATP

Glu, AMP + PPi

Question 8

In the IMP biosynthesis pathway, glutamine is turned to glutamate with what enzyme?

Answer 8

glutamine-PRPP amidotransferase

Question 9

What are building blocks of IMP?

Answer 9

○ Co2
		○ Glycine
		○ Formyl-THF
		○ Glutamine
		○ Aspartate

Question 10

What are 2 major Enzymes in the IMP biosynthesis pathway?

Answer 10

glutamine-PRPP amidotransferase

adenylosuccinate lyase

Question 11

What does adenylosuccinate lyase do?

Answer 11

Creates AMP and fumarate in the IMP biosynthesis pathway. In addition it incorporates an aspartate

Question 12

What does glutamine-PRPP amidotransferase do?

Answer 12

conversts glutamine to glutamate in the IMP biosynthesis pathway

Question 13

How do the products of the IMP pathway (GMP and AMP) balance each other out?

Answer 13

GMP conversts to GTP which drives the other reaction. AMP turns into ATP which drives the other reaction. Buildup of either reaction inhibits itself and drives the other

Question 14

Each product of IMP (GMP or AMP) utilizes how many Energy equivalents?

Answer 14

one (either GTP or ATP)

Question 15

Does GMP utilize ATP or GTP?

Answer 15

ATP

Question 16

Does AMP utilize ATP or GTP?

Answer 16

GTP

Question 17

In the creation of IMP and the regulation of GMP and AMP Synthesis what inhibits PRPP from turning into 5 phosphoribosylamine via glutamine PRPP amido transferase.

Answer 17

AMP, GMP, IMP

Question 18

In the creation of IMP and the regulation of GMP and AMP Synthesis what inhibits IMP dehydrogenase ( turning IMP to XMP)

Answer 18

GMP

Question 19

In the creation of IMP and the regulation of GMP and AMP Synthesis what inhibits adenylosuccinate synthetase ( turning IMP to AMP)

Answer 19

AMP

Question 20

In pyrimidine biosynthesis, what contributes to the ring structure?

Answer 20

glutamine, CO2 (via carbamoyl phosphate), Ribose 5-phosphate and aspartate.

Question 21

What are the 2 main components of the UMP synthesis pathway?

Answer 21

carbamoyl phosphate and Aspartate

Question 22

The purine ring is synthesized on ribose, while the pyrimidine is synthesized when?

Answer 22

before the ribose is added

Question 23

The carbamoyl phosphate for pyrimidine synthesis is made where?

Answer 23

in the cytoplasm

Question 24

In UMP synthesis, apartate transcarbamoylase (ATCase) is inhibited by what?

Answer 24

CTP

Question 25

The UMP synthesis pathway begins with what three things?

Answer 25

carbamoyl phosphate, aspartate, and orotic acid

Question 26

In the UMP synthesis pathway, what enzyme utilizes aspartate to convert Carbamoyl phosphate?

Answer 26

Aspartate transcarbamoylase (ATCase)

Question 27

When does PRPP come into the UMP synthesis pathway?

Answer 27

after orotate

Question 28

ATP + AMP -> 2ADP | What is this?

Answer 28

an adenylate kinase

Question 29

ATP + NMP ->ADP + NDP | What is this?

Answer 29

nucleoside monophosphate kinases

Question 30

ATP + NDP ->ADP + NTP | What is this?

Answer 30

Nucleoside diphosphate kinases

Question 31

UTP->CTP | What is this?

Answer 31

cytidylate synthetase

Question 32

ATP + AMP -> 2ADP ATP + NMP ->ADP + NDP ATP + NDP ->ADP + NTP UTP->CTP These are all ways to form what?

Answer 32

NTPs

Question 33

There is a large sequence of (blank) reactions that occur in the process of removing the oxygen to make dNDP for DNA.

Answer 33

oxidation reduction

Question 34

The heterocyclic ring systems of purines and pyrimidines are assembled form (blank), whereas the ribose portion of the nucleotides comes from (blank).

Answer 34

Simple precursors. | PRPP

Question 35

(blank) is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides.

Answer 35

ribonucleotide reductase

Question 36

the ribonucleotide reductase consists of a large RNR1 and small RNR2 subunits which associate to form an active heterodimeric tetramer What are they and what do they do?

Answer 36

``` RNR1= have regulatory sites and allosteric sites, binds ATP, dGTP,dATP,dTTP,dATP RNR2= active site ```

Question 37

The creation of deoxyribonucleoside diphosphates are highly what?

Answer 37

regulated

Question 38

In thymidylate synthesis, what inhibits thymidylate synthase resulting in decreased amount of dTMP?

Answer 38

5-fluorouracil

Question 39

In the thymidylate synthesis, how is dTMP formed?

Answer 39

DHF is recycled via dihyrdofolate reductase which makes methylene THF which reacts with dUMP and thymidylate synthase to create dTMP

Question 40

THF requires what?

Answer 40

folic acid

Question 41

To salvage RNA and DNA molecules what 3 things do you need?

Answer 41

G/HX-PRT, A-PRT, Pyrimidines need orotic acid transferase

Question 42

What are the steps in cytosine and uracil degradation?

Answer 42

cytosine->uracil->dihydrouracil->carbamoyl beta-alanine-> acetyl-SCoA

Question 43

What is important about thymine degradation?

Answer 43

It makes methylmalonyl semialdehyde which is converted to succinyl sCOA which needs B12 so if you have a B12 deficiency you will have issues

Question 44

What is the common product between GMP and AMP degredation?

Answer 44

Xanthine

Question 45

Why is the GMP and AMP degredation clinically relevant?

Answer 45

because it results in uric acid and a build up of this can lead to gout. People treat gout by inhibiting Xanthine pathway

Question 46

What are three treatments to gout?

Answer 46

Colchicine: anti-inflammatory Probenecid: Increases uric acid excretion Allopurinol: Xanthine oxidase inhibitor

Question 47

WHat is gout?

Answer 47

the build up of uric acid at low ph which forms crystals that can irritate joints

Question 48

B12 is required by what?

Answer 48

methylmalonyl CoA mutase and methionine synthetase

Question 49

If B12 is lacking what clinically will occur?

Answer 49

pernicious anemia autoimmune disease that destroys parietal cells, megaloblastic anemia, neurological dysfunction, deficiency of folate.

Question 50

B12 is utilized in what three types of reactions?

Answer 50

methionine synthesis, thymine degredation, valine isoleucine threonine degredation

Question 51

What does B12 do in the methionine synthesis pathways?

Answer 51

converts homcysteine and metyhl-THF into THF and methionine

Question 52

What does B12 do in the Thymine degredation?

Answer 52

methylmalonylsemialdehyde to succinyl-SCoa

Question 53

What does B12 do in the valine, isoleucine, threonine degradation pathway?

Answer 53

turns methylmalonyl-coa into succinyl coa

Question 54

Folate deficiency decreases (blank) and dTMP synthesis, arresting cell cycle in the S-phase and resulting in megaloblastic anemia.

Answer 54

purine

Question 55

Folic acid is important in what?

Answer 55

THF

Question 56

What does THF do?

Answer 56

It is a one carbon carrier involved in amino acid metabolism and nucleotide synthesis

Question 57

Where do we get folic acid?

Answer 57

yeast, liver, fruits, green vegetables

Question 58

What are the clinical consequences of not having enough folic acid?

Answer 58

Impaired dTMP synthesis, megaloblastic anemia (arrests RBC’s in S phase). Hyperhomocysteinemia with increased risk for cardiovascular disease. Deficiency in pregnancy can lead to neural tube defects (spina bifida) in baby.

Question 59

Explain how folic acid deficiency influences purine synthesis

Answer 59

Folic acid is needed to create THF, since THF is a necessary reactant in the Purine synthesis pathway, this will decrease purine synthesis and arrest cell cycle in the S phase resulting in megablastic anemia.

Question 60

What is the ATP requirement for purine biosynthesis?

Answer 60

5

Question 61

What are the key regulated steps in purine synthesis?

Answer 61

Rate limiting step is the very first step of having glutamine to glutamate which is regulated by NTP, NDP, NMP. If a lot of these it will inhibit the pathway. If PRPP is elevated it will be upregulated. Folic acid deficiency will inhibit creation of THF

Question 62

The (blank) base is synthesized prior to addition of the ribose moiety. Whereas Purine synthesis begins with the ribose moiety.

Answer 62

pyrimidine

Question 63

(blank) inhibits dihydrofolate reductase competitively, thereby depleting the cell of tetrahydrofolate.

Answer 63

Methotrexate

Question 64

(blank) is inhibited by the antineoplastic agent 5-fluorouracil (5-FU). 5-FU is converted by (blank) to 5-FdMP, which remains bound to the enzymes, as a suicide inhibitor. 5-FU is an important agent in the treatment cancers such as breast and colon cancer.

Answer 64

Thymidylate synthase | Thymidylate synthase

Question 65

Allopurinol is used as a treatment for gout. Describe the mechanism in the context of GMP and AMP degradation. 

Answer 65

GMP and AMP degredation results in uric acid and a build up of this can lead to gout. People treat gout by inhibiting Xanthine pathway allopurinol is a Xanthine oxidase inhibitor.