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Heme Midterm 1 > Pyrimidine Synthesis and Salvage Pathways > Flashcards

Pyrimidine Synthesis and Salvage Pathways Flashcards

1
Q

what are the 3 salvage pathways for nucleotides?

A

base to nucelotide
nucleoside to nucleotide
nuceloside to base to nucleotide

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2
Q

what enzyme turns adenine into AMP?

A

APRT

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3
Q

what enzyme turns hypoxanthine into IMP and guanine into GMP?

A

HGPRT

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4
Q

what do you need to help turn a base into a nucelotide?

A

PRPP

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5
Q

what enzyme turns a nucleoside into a free base?

A

purine nucleoside phosphorylase

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6
Q

if purine nuceloside phosphorylase is deficient…what builds up?

A

purine nucleosides, specifically toxic is build up of dGTP

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7
Q

What does buildup of dGTP come from and what does it cause?

A

purine nuceloside phosphorylase is deficienct so nucleoside building up

can lead to T cell issues

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8
Q

How does gout relate to PRPP synthetase?

A

if PRPP synthetase is mutated you can have over activity of it leading to extra PRPP and increased production of purines that can contribute to gout

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9
Q

how does glucose-6-phosphatase deficiency lead to gout? and what is the name of this disease?

A

it means you cannot send glucose into glycolysis and it forces more down pentose phosphate pathway leading to excess nucleotides and gout

von gierke disease

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10
Q

How does a problem with HGPRT lead to gout? What is this disease called? What is the diseases genetics?

A

you cannot salvage the guanine and hypoxanthine so these get broken down into uric acid instead

Lesch Nyhan

X linked recessive

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11
Q

allopurinol drug use and mechanism

A

treats gout by inhibiting uric acid synthesis by inhibiting Xanthine oxidase

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12
Q

febuxostate drug use and mechanism

A

also treats gout by inhibiting Xanthine oxidase and preventing uric acid synthesis

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13
Q

do purines or pyrimidines production start with a ribose backbone?

A

purines start with it and pyrimidines add it later

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14
Q

what is needed to make the pyrimidine ring?

A

aspartate, glutamine and CO2

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15
Q

what is the first step in pyrimidine synthesis?

A

glutamine, CO2 and phosphate turned into carbamoyl phosphate by CPS-II

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16
Q

what is the enzyme for the first step in pyrimidine synthesis?

A

CPS-II

17
Q

what are the second and third steps in pyrimidine synthesis?

A

turn carbamoyl phosphate into carbamoyl aspartate and then turn carbamoyl aspartate into orotic acid

18
Q

what is orotic acid?

A

the main precursor for pyrimidine molecules..it leads to UMP

19
Q

What is hereditary orotic aciduria?

A

when you have issue with enzyme that changes orotic acid into nucleotides you get build up of orotic acid

20
Q

What step is the committed step pyrimidine synthesis?

A

CPS II enzyme step…step 1

21
Q

what can activate and what can inhibit CPS-II in pyrimidine synthesis?

A

PRPP activates

nucleotides inhibit

22
Q

how do we make CTP from UTP?

A

using an enzyme called CTP synthetase

23
Q

What are CTP and UTP degraded into? and what is this molecule useful for?

A

malonyl CoA

Malonyl CoA is involved in fatty acid synthesis

24
Q

What is thymine degraded into? and what is this molecule used for?

A

methylmalonyl coa which can be made into succinyl CoA which can be used for krebs cycle

25
Q

What is the salvage pathway for pyrimidines?

A

bases turned into nucleosides and then nucleosides into nucleotides

26
Q

how do we turn nucleotides into deoxyribonucleotides?

A

using an enzyme call ribonucleotide reductase

27
Q

what is unique about ribonucelotide reductase?

A

it only works to reduce ribonucleotides with two phosphates

28
Q

what inhibits the ribonucleotide reductase?

A

hydroxyurea, which inhibits production of DNA…anti tumor

29
Q

What are the two pathways to turn UDP into dUMP?

A

can either go directly with UDP to dUDP to dUMP

or can turn into CDP then dCDP then dCMP then dUMP

30
Q

what molecule turns dCMP into dUMP?

A

dCMP deaminase

31
Q

what is needed to turn dUMP into dTMP?

A

tetrahydrofolate

32
Q

what molecule activates and what molecule inhibits ribonucleotide reductase?

A

ATP activated

dATP inhibits

33
Q

Why does ribonucelotide reductase have two specific binding sites?

A

one for either activation or inhibition by ATP or dATP

one for determining what the preferred substrate is…as different nucleotides bind it prefers other nucleotides

34
Q

mechanism of 5-fluorouracil?

A

anti tumor drug by inhibiting synthesis of thymidine

35
Q

mechanism of methotrexate?

A

inhibits dihydrofolate reductase so cannot make thymidine

36
Q

mechanism of 6-mercaptourine?

A

inhibits the glutamine phosphoribosyl amidotransferase that is committed step in purin synthesis so inhibits purines

37
Q

mechanism of leflunomide?

A

inhibits production of orotate so inhibits production of pyrimidines

Heme Midterm 1 (11 decks)

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