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SFM > (L8) Nucleotide Metabolism > Flashcards

(L8) Nucleotide Metabolism Flashcards

1
Q

What are the purines and pyrimidines?

L8 S4 LO1

A

Purines (two-membered ring):

  • adenine
  • guanine

Pyrimidine (one-membered ring):

  • cytosine
  • uracil
  • thymine
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2
Q

Differentiate between nucleotides and nucleosides.

L8 S4 LO1

A

Nucleoside:

  • nitrogenous base
  • sugar

Nucleotide

  • nitrogenous base
  • sugar
  • phosphate
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3
Q

What is the energy in the bonds between each phosphate in a nucleotide?

L8 S7 LO1

A

ATP -> ADP + Pi -7.3kcal/mol

ATP -> AMP + PPi -10.9kcal/mol

PPi -> Pi + Pi -4.0kcal/mol

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4
Q

What cofactors are derived from nucleotides?

L8 S9 LO1

A
  • CoA
  • FAD
  • FMN
  • NADPH
  • NADH
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5
Q

What are the atom sources of purine rings?

L8 S218 LO2

A
  • Aspartate
  • CO2
  • Glutamine
  • Glycine
  • N10-formyl-tetrahydrofolate
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6
Q

What are the steps of purine synthesis?

L8 S18 LO2

A
  • activation of ribose 5-phosphate to PRPP
  • addition of amine to PRPP
  • production of IMP
  • conversion of IMP to AMP or GMP

Sugar is made first

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7
Q

What is the rate limiting step of purine synthesis?

L8 S20 LO2

A

Glutamine:phosphoribosyl pyrophosphate amidotransferase

PRPP -> PRA

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8
Q

How is purine synthesis regulated?

L8 S23 LO2

A

PRPP production and conversion is inhibited by IMP, AMP, and GMP (if you have them you don’t need more)

AMP and GMP are inhibited by themselves (if you have enough of one you don’t need more of it, you need more of the other)

Conversly, AMP and GMP produciton are stimualted by the other (if you have enough of one, you need more of the other)

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9
Q

What noteworthy features are there about the conversion of IMP to either ATP or GTP?

L8 S22 LO2

A

ATP:

  • uses GTP for energy
  • regenerates fumarate (TCA)
  • goes through adenyloxuccinate intermediate

GTP:
-uses ATP for enery

  • uses NAD+
  • goes through XMP intermeidate
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10
Q

What are the atom sources of pyrimadine rings?

L8 S24 LO2

A
  • Carbamoyl phosphate
  • Aspartate
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11
Q

What are the steps of pyrimidine synthesis?

L8 S24 LO2

A
  • pyrimidine ring formation as orotate
  • attachment of orotate to PRPP making UMP
  • conversion of of UMP to TMP or CMP

Ring is made first

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12
Q

Which nucleotides require folate derivatives to be synthesized?

L8 S21; 27 LO2

A
  • IMP
  • ATP (IMP derivative)
  • GTP (IMP derivative)
  • TTP
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13
Q

What is the rate limiting step of pyrimidine formation?

L8 S25 LO8

A

Carbamoyl phosphate synthetase II

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14
Q

What is the purpose of the dUDP loop in pyrimidine synthesis?

L8 S27 LO2

A

Keeps dUTP level low to prevent it from being incorporated into DNA

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15
Q

What are the inhibitory step of pyrimidine synthesis?

L8 S28 LO2

A

Carbamoyl phosphate:

  • inhibited by UMP/UTP
  • stimulated by PRPP

Aspartate transcarbamoylae:

-inhibited by CTP

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16
Q

What is methotrexate and what is it used for?

L8 S31 LO2

A

Structurally similar to folic acid.

Tightly binds dihydrofolate reductase which inhibits ATP, GTP, and TTP production.

This is used to kill rapidly dividing cells, such as cancer.

17
Q

What are sulfa drugs and what are they used for?

L8 S32

A

Antibacterial that inhibtis bacterial DNA replicaion by inhibiting enzyme that incorperates p-aminobenzoic acid (PABA) into folate

Does not affect humans as we do not synthesize folate

18
Q

What is acyclovir and what is it used for?

L8 S33 LO2

A

Antiviral which targes viral thymidine kinase causes it to be phosphorylated.

When incorperated into viral DNA, it terminates transrciption due to lack of 3’ OH

19
Q

How are purines catabolized?

L8 S35 LO3

A

GMP and AMP are both converted into xanthine which is then converted into uric acid.

20
Q

What is SCID?

L8 S38 LO3

A

Severe combined immunodeficiency

Deficiency of ADA from adenine degradation pathway which lead to build of of dATP which inhibits formation of other dNTPs.

Results in compromise in both T and B cells leading to severe immune deficiecny.

Most commonly affects males as the most common form is X-linked

21
Q

What is gout?

L8 S39 LO3

A

Caused by crystaliztion of excess uric acid, most commonly in toes, which can cause extreme pain.

Uric acid is produced during purine degrataion by xanthine oxidase

22
Q

How are pyrimidines catabolized?

L8 S40 LO3

A

Converted to malonyl CoA:

  • uracil
  • cytosine

Converted to methylmalonyl CoA or succinyl CoA:

-thymine

23
Q

What are the main nucleotide salvage pathways?

L8 S42 LO4

A

AMP:

-adenine phosphoribosyltransferase (APRT)

GMP and IMP:

-hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

24
Q

What is Lesch-Nyhan syndrome?

L8 S43 LO4

A

Results from <1.5% normal HGPRT activity (GMP/IMP salvage pathway) resulting in hyperuricemia.

Clinical features:
-self-mutilation

  • poor muscle control
  • MR

Gout like features can be lessend by allopurinal treatment

25
Q

What is acheived by inhibiting GMP and dGTP production and how is it done?

L8 S33

A

Doing so especially effects lymphocytes, limiting their replicaiton.

This can be used as an immuosuppresant to prevent transplant rejection.

It is done by targeting IMP dehydrogenase (IMP -> XMP)

SFM (31 decks)

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