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DEMS Unit 2 Part 2 > Purines and Pyrimidines > Flashcards

Purines and Pyrimidines Flashcards

1
Q

Describe the function of the antiporter ORNT1

A

Ornithine is transported in

Citrulline is transported out

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2
Q

What happens if you cannot run the urea cycle?

A

Cannot get nitrogen out, get a buildup of ammonia, which is toxic

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3
Q

Which organ is the main site of the urea cycle? How do you get nitrogen there?

A
  • The liver
  • get nitrogen to the liver via Glutamine (extra nitrogen relative to glutamate)
  • Also can get delivery through alanine via a transamination reaction (recall that alanine can be produced from pyruvate!)
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4
Q

What are the control points for protein catabolism?

A
  1. Transaminases
  2. Carbamoyl phosphate synthetase I
    3 & 4) Glu dehydrogenase

Refer to the figure for where these number occur

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5
Q

Creatine phosphate

A

Creatine phosphate - high energy phosphate form, reservoir in the muscle, used during exercise

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6
Q

Branched Chain Amino Acids

A

They are:

  • Val
  • Ile
  • Leu

Remove nitrogen through transamination. Get an alpha-ketoacid. You can then take this into Krebs for gluconeogenesis.

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7
Q

Which enzyme is broken in MSUD?

A

branched-chain alpha-keto acid dehydrogenase complex

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8
Q

What alpha-ketoacid do we see used in the TCA cycle regularly?

A

Pyruvate

If we used PDHC, then you would go from pyruvate –> acetyl-CoA; this is similar to what we are doing with the other branched chain AAs now. Just trying to get into the TCA cycle

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9
Q

PURe As Gold; CUT the Py

A

Purines: Adenine and Guanosine
Pyrimidines: Cytosine, Uracil, Thymidine

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10
Q

Which pyrimidines are in RNA vs. DNA

A

RNA:

  1. UMP
  2. CMP

DNA:

  1. CMP
  2. TMP
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11
Q

What is the difference between nucleoside and nucleotide?

A 
Nucleoside = Base + Sugar 
Nucleotide = Base + Sugar + Phosphate

Can either build sugar and put a base on it or build a base and put a sugar on it

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12
Q

Where does the Urea Cycle occur?

A

The mitochondria and cytosol

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13
Q

Key differences in purine and pyrimidine nucleotide de novo synthesis:

A

Purine:

  • Purine base made on the ribose
  • initial nucleotide product is IMP
  • I is converted to G and A as a monophosphate

Pyrimidine:

  • Base ring is synthesized then attached to the ribose
  • Initial nucleotide product is UMP
  • U is converted to C as a triphosphate
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14
Q

De novo synthesis of purines:

A
  1. Get ribose sugar from HMP Shunt (key enzyme: G6PD)
  2. Ribose 5-phosphate –(PRPP Synthetase)–> 5-Phosphoribosyl-1-pyrophosphate (PRPP); key step because this requires ATP
  3. PRPP –(Glutamine phosphorphoribosyl pyrophosphate aminotransferase)–> 5’-Phosphoribsoylamine; key step because this is at the front end and is allosterically regulated
  4. End at IMP
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15
Q

What activates and inhibits PRPP synthase

A
  1. Activation by Pi
  2. Inhibition by purine ribonucleotides (end product inhibition)

First step is allosterically regulated

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16
Q

What activates and inhibits glutamine phosphoribosyl pyrophosphate aminotransferase?

A

Activate:
1. PRPP

Inhibit:

  1. AMP
  2. GMP
  3. IMP
17
Q

Sources of atoms for purine synthesis

A
  1. Glutamine
  2. Glycine
  3. Aspartate
  4. THF (methyl donor)
  5. CO2
18
Q

Converting IMP to AMP and GMP

A

Need to get extra nitrogens hooked on

AMP and GMP come from IMP, and there is feedback inhibition from end-products

Source of energy:

  1. For AMP production: uses GTP
  2. For GMP production: uses ATP

If you have a lot of AMP, then you will shift to making more GMP and vice versa

19
Q

Generating Di and Tri-Phosphate forms

A

The following get us to the diphosphate form:

  • Adenylate kinase
  • Guanylate kinase

This gets us to the triphosphate form:

  • Nucleoside diphosphate kinase
  • ATP acts as energy donor to get the other ribonucleotides to the triphosphate form
20
Q

Carbamoyl phosphate synthetases

A
  1. 2ATP + CO2 + glutamine –(Carbamoyl phosphate synthetase II) –> Carbamoyl phosphate

Note:

  • Carbamoyl phosphate synthetase I is in the mitochondria and is part of urea. Uses Ammonia as source of nitrogen and is activated by N-acetyl-glutamate.
  • Carbamoyl phosphate synthetase II is in the cytosol and is part of pyrimidine biosynthesis. Uses gamma-amide group of glutamine and is inhibited by UTP (end product inhibition) and activated by ATP
21
Q

Pyrimidine synthesis (Cytosol)

A
  1. 2 ATP + CO2 + Glutamine – (Carbamoyl phosphate synthetase II)–> Carbamoyl phosphate; key step because energy invested as 2 ADP
  2. Get finished base (orotate) + add PRPP –> OMP –> UMP
  3. Ends at UMP
22
Q

Sources of atoms for pyrimidine synthesis

A
  1. CO2 and glutamine
  2. Aspartate
  3. Ribose sugar is added last
23
Q

Synthesizing CTP from UTP

A

UTP – (CTP synthetase)–> CTP

  1. Uses Glutamine -> Glutamate
  2. Requires ATP
24
Q

Conversion or ribonucleotides to deoxyribonucleotides

A
  1. Ribonucleoside diphosphate –(Ribonucleotide reductase)–> deoxyribonucleoside diphosphate
25
Q

On/Off sites and regulation of ribonucleotide reductase

A
  1. Activity sites (on/off switch)
    - ATP activates the enzyme
    - dATP inhibits the enzyme
    so based off of the ratio of dATP:ATP
  2. Substrate specificity sites (determine which one is made)
    - ATP, dATP, dTTP, or dGTP regulate the reduction of specific deoxyribonucleotides
26
Q

Without U there’s no T… what am I referring to?

A

You can’t make dTMP or dTTP without first going through dUMP.

UMP->UDP->dUDP->dUMP->dTMP->dTDP->dTTP

27
Q

Things to remember about mono and di…

A
  1. Ribonucleotide reductase uses dNDP or NDP (diphosphate)

2. UTP -> CTP

28
Q

THF’s role in U–>T

A

THF is a methyl donor

  1. dUMP –(THF)–> dTMP
  2. N5, N10 THF –> Dihydrofolate –> THF to recycle it.

Note: methotrexate inhibits THF recycling to N5,N10 THF, which is why it is used against cancer cells.

29
Q

Degradation of purine and pyrimidines

A

Channel the base into uric acid

  1. PRPP –> IMP –> inosine OR you can do step 2
  2. AMP –> adenosine –(adenosine deaminase)–> inosine
  3. Inosine – (purine nucleoside phosphorylase) –> hypoxanthine
  4. Hypoxanthine –(xanthine oxidase)–> xanthine
  5. Xanthine – (xanthine oxidase)–> uric acid
30
Q

Deficiency of adenosine deaminase results in what?

A

Accumulation of dADP or dAMP and poisons ribonucleotide reductase.

Results in SCID!

31
Q

Allopurinol is used to treat what disease process, and which enzyme specifically?

A

Tx for gout via xanthine oxidase

32
Q

2 key enzymes in purine and pyrimidine degradation?

A
  1. ADA (adenosine deaminase)

2. Xanthine oxidase

33
Q

HGPRT deficiency results in what?

A

Inability to salvage hypoxanthine or guanine

Need to do a bunch of de novo synthesis, this results in excessive production of uric acid –> Lesch-Nyhan

34
Q

Salvage pathways

A

Adenine phosphoribosyl transferase:
- Adenine + PRPP –> AMP + PPi

HGPRTase:

  • Hypoxanthine + PRPP –> IMP + PPi
  • Guanine + PRPP –> GMP + PPi

Note: we can also salvage U, C, and T

DEMS Unit 2 Part 2 (22 decks)

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