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Biochemistry > Purines and Pyrimidines > Flashcards

Purines and Pyrimidines Flashcards

1
Q

What are the purines?

A
  • 2 rings
  • adenine
  • guanine
  • xanthine
  • hypoxanthine
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2
Q

What are the pyrimidines?

A
  • one ring
  • cytosine
  • uracil (in RNA)
  • thymine
  • orotic acid
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3
Q

What are nucleosides?

A

sugar moiety added to purine or pyrimidine

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4
Q

What are nucleotides?

A

phosphate group on sugar of nucleoside

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5
Q

What are the important signaling molecules?

A
  • cyclic adenosine monophosphate (cAMP)
  • guanosine tripohosphate (GTP)
  • guanosine diphosphate (GDP)
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6
Q

What are the types of sources of energy in cells?

A
  • GTP -> in protein metabolism
  • CTP -> in lipid metabolism
  • UTP -> in glucose and galactose activation
  • NADH -> electron tranpsort chain
  • FADH2 -> redox factor
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7
Q

What 2 things are the stimulatory ingredients in coffee/tea?

A

caffeine and purines

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8
Q

Where does purine metabolism occur?

A

in liver -> cytoplasm

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9
Q

Where does pyrimidine metabolism occur?

A

in liver/other tissues -> cytoplasm and mitochondria

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10
Q

Where do the de novo and salvage pathways occur?

A
  • salvage: extrahepatic tissue
  • de novo: in liver
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11
Q

What are the steps of the purine de novo pathway?

A
  1. starts from pentose 5-phosphate
  2. catalyzed by PRPP synthetase to create PRPP
  3. PRPP catalyzed by glutamine PRPP-amidotransferase to create PRA
  4. PRA catalyzed by amino acids Gln, Gly, and Asp
  5. PRA creates IMP -> GMP and AMP
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12
Q

What is the committed step in the purine de novo pathway?

A

PRPP -> glutamine PRPP-amidotransferase -> PRA; high energy consuming step

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13
Q

What is the first nucleotide formed in purine biosynthesis?

A

IMP which can create GMP and AMP

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14
Q

How is GMP formed from IMP?

A

IMP -> IMP dehydrogenase -> XMP -> GMP synthetase with ATP -> GMP

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15
Q

How is AMP formed from IMP?

A

IMP -> adenylosuccinate synthetase with GTP -> adenylosuccinate sAMP -> adenylosuccinase -> AMP

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16
Q

Where do all purine nitrogens come from?

A

amino acids glutamine, aspartate, and glycine

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17
Q

When does a feed-forward activation occur in the regulation of de novo purine synthesis?

A

when PRPP is increased

18
Q

What happens in feedback inhibition in the regulation of de novo purine synthesis?

A
  • when there is too much product
  • GMP inhibits IMP dehydrogenase and glutamine PRPP-amidotransferase
  • AMP inhibits adenylosuccinate synthetase and glutamine PRPP amidotransferase
19
Q

The purine salvage pathway accounts for how much of daily nucleotide biosynthesis?

A

90%

20
Q

Which pathway is highly efficient and requires litte energy?

A

purine salvage pathway

21
Q

What is the purine salvage pathway?

A

free purine bases attached to PRPP use APRT and HGPRT to form purine nucleoside monophosphates

22
Q

What is the pathway of purine catabolism?

A

hypoxanthine -> xanthine oxidase -> xanthine -> xanthine oxidase -> uric acid

23
Q

What is uric acid excreted by?

A

kidneys

24
Q

What are the 2 diseases associated with purine metabolism?

A

gout and Lesch-Nyhan syndrome

25
Q

What is gout?

A
  • excess urate forms crystals in joints
  • high urate causes kidney stones
  • symptoms: inflammation, intense joint pain, limited range of motion
26
Q

What are the treatments for gout?

A
  • inhibit xanthine oxidase and reduce production of uric acid
  • allopurinol as a protein inhibitor of xanthine oxidase
  • probenecid
  • NSAIDs, colchine, corticosteroids reduce inflammation
27
Q

What is Lesch-Nyhan syndrome?

A
  • x-linked recessive
  • deficiency of HGPRT enzyme
  • symptoms: sand-like uric acid crystals
28
Q

What is the treatment for Lesch-Nyhan syndrome?

A

allopurinol -> DOES NOT resolve neurological and behavioral symptoms

29
Q

What are the steps in the pyrimidine de novo pathway?

A
  1. carbamoyl phosphate is produced from bicarb. and ammonia OR glutamine and CO2
  2. carbamoyl phosphate -> aspartate transcarbamylase (ACTase) -> N-carbamoylaspartate
  3. N-carbamoylaspartate -> dihydroorotase -> dihydroorotate -> dihydroorotate dehydrogenase -> orotic acid
  4. orotate phospho ribosyl -> O-PRT -> orotidine 5 monophosphate -> OMP decarboxylase -> UMP
30
Q

What enzyme is carried out by N and C terminal?

A
  • N terminal -> O-PRT
  • C-terminal -> OMP decarboxylase
31
Q

What is the first nucleotide of the pyrimidine de novo pathway?

A

UMP

32
Q

What is the first product of the pyrimidine de novo pathway?

A

orotic acid

33
Q

What is the role of uridine 5’monophosphate synthase in the pyrimidine de novo pathway?

A
  • bifunctional enzyme
  • N-terminal orotate phosphoribosyl transferase converts orotic acid to orotidine 5’ monophosphate
  • C-terminal OMP decarboxylase converts orotidine 5’ monophosphate to UMP
34
Q

What is the main difference purine and pyrimidine de novo pathways?

A
  • purine ring built on PRPP
  • pyrimidine ring formed FIRST and then transferred to PRPP
35
Q

What is the pyrimidine salvage pathway for UMP?

A

free bases + PRPP -> pyrimidine nucleoside phosphorylases -> uridine/cytidine -> uridine kinase -> UMP

36
Q

What is the pyrimidine salvage pathway for TMP?

A

thymine + PRPP -> pyrimidine nucleoside phosphorylases -> uridine/cytidine -> thymidine kinase -> TMP

37
Q

What is the process of RNA pyrimidine catabolism?

A

RNA -> nucleases -> CMP & UMP -> uracil -> NADP -> beta alanine (product)

38
Q

What is the process of DNA pyrimidine catabolism?

A

DNA -> nucleases -> dCMP & dTMP -> dUMP -> thymine -> NADP -> beta-aminoisobutyrate (product)

39
Q

What is the disease associated with pyrimidines?

A
  • uridine monophosphate synthase deficiency
  • accumulation of orotic acid
40
Q

What is the treatment for uridine monophosphate synthase deficiency

A

Xuriden: oral uridine supplementation

Biochemistry (20 decks)

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