Nucleotide Metabolism Flashcards

1
Q

What are DNA and RNA made from?

A

Nucleotides

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2
Q

What roles do nucleotides play?

A
  • Carriers of activated intermediates in synthesis of carbs, lipids and conjugated proteins
  • Structural components of several essential coenzymes (CoA, FAD, NAD + NADP, UDP-glucose)
  • Second messengers (cAMP, cGMP)
  • Energy currency (ATP)
  • Regulatory compounds (ATP when E high, AMP when E low)
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3
Q

Why do we need to get nucleotides de novo or through salvage pathways?

A

We eat a ton of nucleotides but we don’t absorb them -> intestines eliminate them

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4
Q

What are the purines?

A

Adenine and guanine

-2 rings

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5
Q

What are the pyrimidines?

A

Thymine, cytosine, and uracil (RNA)

-1 ring

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6
Q

What are nucleosides?

A

Pentose sugar (from PPP) + base (through glycosidic bond)

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7
Q

What are nucleotides?

A

1 or more phosphate group + nucleoside

  • Named by # of phosphates (adenosine monophosphate = AMP, adenosine diphosphate = ADP…)
  • Phosphates have high-energy bonds
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8
Q

What is the nucleoside of base adenine?

A

Adenosine

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9
Q

What is the nucleoside of base guanine?

A

Guanosine

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10
Q

What is the nucleoside of base cytosine?

A

Cytidine

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11
Q

What is the nucleoside of base thymine?

A

Thymidine

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12
Q

What is the nucleoside of base uracil?

A

Uridine

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13
Q

What is the nucleoside of base hypoxanthine?

A

Inosine

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14
Q

What is purine made from?

A

3 AAs (Aspartate, Glycine and Glutamine) + CO2 + N-Formyl Tetrahydrofolate (FH4)

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15
Q

What happens first in the making of a purine?

A

Activate Ribose 5-phosphate by PRPP Synthetase using ATP -> PRPP
-Regulated step, but NOT committed

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16
Q

What is the committed step in the making of a purine?

A

PRPP reacts w/ glutamine to form phosphoribosylamine -> nitrogen 9 of purine ring

  • Catalyzed by glutamine phosphoribosyl amidotransferase
  • Uses H2O and Glutamine -> Glutamate
17
Q

What is the first final purine product?

A

IMP (contains the base hypoxanthine joined to sugar)

-From here we either make Adenine or Guanine (purines)

18
Q

What does the drug Methotrexate do?

A

Blocks the use of tetrahydrofolate -> limits purine synthesis -> blocks DNA replication

  • Useful in treating cancer but is not specific to just cancer cells
  • Ex. of folic acid analog
19
Q

How are the majority of dietary nuclei acids degraded in the small intestine?

A

Converted to uric acid in intestinal mucosal cells -> blood -> urine

20
Q

Are dietary bases used for synthesis of tissue nucleic acids?

A

No, but the small intestine can use a small amount of it for its own need (regeneration of intestinal lining) -> the rest converted to uric acid

21
Q

What is gout?

A

Disorder of hyperuricemia w/ recurrent attacks of acute arthritis joint inflammation, caused by deposition of mono-sodium urate crystals

22
Q

What does gout result from?

A

Under excretion of uric acid

23
Q

What enzyme is important in the conversion of purines to uric acid?

A

Xanthine oxidase

24
Q

What is used to treat acute attacks of gout?

A

Anti-inflammatory agents (colchicine, steroidal drugs-prednisone, non-steroidal drugs-indomethacin)

25
Q

What is used for long-term therapeutic strategies for gout?

A

Allopurinol - structural analog of hypoxanthine

-Inhibits xanthine oxidase -> reduces uric acid production

26
Q

What is required for an official diagnosis of gout?

A

Arthrocentesis of joint fluid

-Helps define causes of joint swelling/arthritis (infection, gout, rheumatoid disease)

27
Q

What do you require for the making of a pyrimidine?

A

CO2 + Glutamine + Aspartate

28
Q

What is the main difference between making a pyrimidine and making a purine?

A

In making pyrimidine you make the base alone and then you add it to a sugar
-In purine you start by activating the sugar and adding to it

29
Q

What is the regulated step in the making of a pyrimidine?

A

Glutamine + CO2 -> Carbamoyl phosphate

-Catalyzed by carbamoyl phosphate synthetase (CPS) II

30
Q

What are the differences of CPS II and CPS I?

A
  • CPS I: in mitochondria, in urea cycle, FIXES free ammonia

- CPS II: in cytosol, in pyrimidine synthesis, N from gamma-amide group of glutamine (NOT FREE AMMONIA)

31
Q

What is essential for making of DNA and development of neural tube in fetus?

A

When you make UMP to make TMP for DNA synthesis, difference between U and T is methyl Group, donated by tetrahydrofolate

32
Q

What are 3 carbons in our body specialized in transferring?

A

Tetrahydrofolate, Vitamin B12 & S-AM (adenosyl methionine)

33
Q

What causes neural tube defects?

A

In pregnant woman the need for tetrahydrofolate is increased because greater need to make this as fetus grows
-Inhibition of dUMP to dTMP -> neural tube defect

34
Q

What is 5-fluorouracil?

A

Chemotherapy medication

-Inhibits dUMP to dTMP -> stops DNA replication