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Block 1 W5 > Nucleic Acid Metabolism - Biochem > Flashcards

Nucleic Acid Metabolism - Biochem Flashcards

1
Q

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

A

Ribose-5-P and ATP

IMP

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2
Q

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

A

Inhibitors: NTP, NDP, NMP
activators: PRPP

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3
Q

What is Inosinate (IMP) a derivative of?

A

Adenylate (AMP), Guanylate (GMP)

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4
Q

What is added to IMP to create adenylosuccinate?

A

aspartate, GTP, adenylosuccinate synthetase

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5
Q

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

A

adenylosuccinate lyase

fumarate is removed

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6
Q

What is added to IMP to make XMP?

A

H20, NAD+

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7
Q

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

A

Gln, and ATP

Glu, AMP + PPi

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8
Q

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

A

glutamine-PRPP amidotransferase

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9
Q

What are building blocks of IMP?

A 
○ Co2
		○ Glycine
		○ Formyl-THF
		○ Glutamine
		○ Aspartate
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10
Q

What are 2 major Enzymes in the IMP biosynthesis pathway?

A

glutamine-PRPP amidotransferase

adenylosuccinate lyase

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11
Q

What does adenylosuccinate lyase do?

A

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

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12
Q

What does glutamine-PRPP amidotransferase do?

A

conversts glutamine to glutamate in the IMP biosynthesis pathway

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13
Q

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

A

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

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14
Q

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

A

one (either GTP or ATP)

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15
Q

Does GMP utilize ATP or GTP?

A

ATP

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16
Q

Does AMP utilize ATP or GTP?

A

GTP

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17
Q

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.

A

AMP, GMP, IMP

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18
Q

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

A

GMP

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19
Q

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

A

AMP

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20
Q

In pyrimidine biosynthesis, what contributes to the ring structure?

A

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

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21
Q

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

A

carbamoyl phosphate and Aspartate

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22
Q

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

A

before the ribose is added

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23
Q

The carbamoyl phosphate for pyrimidine synthesis is made where?

A

in the cytoplasm

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24
Q

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

A

CTP

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25
Q

The UMP synthesis pathway begins with what three things?

A

carbamoyl phosphate, aspartate, and orotic acid

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26
Q

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

A

Aspartate transcarbamoylase (ATCase)

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27
Q

When does PRPP come into the UMP synthesis pathway?

A

after orotate

28
Q

ATP + AMP -> 2ADP

What is this?

A

an adenylate kinase

29
Q

ATP + NMP ->ADP + NDP

What is this?

A

nucleoside monophosphate kinases

30
Q

ATP + NDP ->ADP + NTP

What is this?

A

Nucleoside diphosphate kinases

31
Q

UTP->CTP

What is this?

A

cytidylate synthetase

32
Q

ATP + AMP -> 2ADP
ATP + NMP ->ADP + NDP
ATP + NDP ->ADP + NTP
UTP->CTP

These are all ways to form what?

A

NTPs

33
Q

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

A

oxidation reduction

34
Q

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

A

Simple precursors.

PRPP

35
Q

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

A

ribonucleotide reductase

36
Q

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?

A 
RNR1= have regulatory sites and allosteric sites, binds ATP, dGTP,dATP,dTTP,dATP
RNR2= active site
37
Q

The creation of deoxyribonucleoside diphosphates are highly what?

A

regulated

38
Q

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

A

5-fluorouracil

39
Q

In the thymidylate synthesis, how is dTMP formed?

A

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

40
Q

THF requires what?

A

folic acid

41
Q

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

A

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

42
Q

What are the steps in cytosine and uracil degradation?

A

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

43
Q

What is important about thymine degradation?

A

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

44
Q

What is the common product between GMP and AMP degredation?

A

Xanthine

45
Q

Why is the GMP and AMP degredation clinically relevant?

A

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

46
Q

What are three treatments to gout?

A

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

47
Q

WHat is gout?

A

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

48
Q

B12 is required by what?

A

methylmalonyl CoA mutase and methionine synthetase

49
Q

If B12 is lacking what clinically will occur?

A

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

50
Q

B12 is utilized in what three types of reactions?

A

methionine synthesis, thymine degredation, valine isoleucine threonine degredation

51
Q

What does B12 do in the methionine synthesis pathways?

A

converts homcysteine and metyhl-THF into THF and methionine

52
Q

What does B12 do in the Thymine degredation?

A

methylmalonylsemialdehyde to succinyl-SCoa

53
Q

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

A

turns methylmalonyl-coa into succinyl coa

54
Q

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

A

purine

55
Q

Folic acid is important in what?

A

THF

56
Q

What does THF do?

A

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

57
Q

Where do we get folic acid?

A

yeast, liver, fruits, green vegetables

58
Q

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

A

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.

59
Q

Explain how folic acid deficiency influences purine synthesis

A

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.

60
Q

What is the ATP requirement for purine biosynthesis?

A

5

61
Q

What are the key regulated steps in purine synthesis?

A

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

62
Q

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

A

pyrimidine

63
Q

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

A

Methotrexate

64
Q

(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.

A

Thymidylate synthase

Thymidylate synthase

65
Q

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

A

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.

Block 1 W5 (11 decks)

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