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MCM Quiz 1 > nucleotide metabolism > Flashcards

nucleotide metabolism Flashcards

1
Q

what is nucleotide structure?

A

nitro base + sugar+ phosphate

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2
Q

what is nucleoside structure?

A

nitro base + sugar

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3
Q

How are purines synthesized?

A
  1. They can be made in the liver or cytosol: purine base formed on r5p from ppp
  2. Salvage: r5p to purine base
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4
Q

How are pyrimidines synthesized?

A
  1. They can be made in the liver or cytosol: pyramidine ring, ribose phosphate added
  2. Salvage: pyrimidine nucleotides made from bases in RNA/DNA
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5
Q

4 Phases of purine synthesis?

A

Phase 1: Activation of r5p

Phase 2: PRPP to PRA

Phase 3: IMP is formed

Phase 4:IMP made into AMP or GMP

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6
Q

What happens in phase 1 of purine syn? + and -?

A

r5p to prpp (PRPP synthetase), needs ATP

+P
-Purine nucleotides

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7
Q

What happens in phase 2 of purine syn? + and -?

A

COMMITTED STEP!!

PRPP to PRA (glutosamine: phosphoribyl pyrophosphate)
-Needs Gln

+ PRPP
-Nucleotides

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8
Q

What happens in phase 3 of purine syn? + and -?

A

PRA to IMP

  • 9 steps to make ring
  • uses ATP to make ring

-methotrexate

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9
Q

What happens in phase 4 of purine syn? + and -?

A

IMP to

dATP (adenylylsuccinate ynthetase)
-AMP

or

dGTP (IMP dehydrogenase)

  • needs GTP
  • GMP
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10
Q

How is Purine synthesis regulated?

A

*Own products inhibit synthesis

  • AMP stopped by GTP
  • GMP stopped by ATP
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11
Q

4 steps of pyrimidine synthesis?

A

Phase 1: pyrimidine ring made as orotate

Phase 2: orotate attaches to PRPP to become UMP

Phase 3: UMP becomes TMP or dCTP

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12
Q

What is phase 1 of pyrimidine synthesis? what + and -? whats significance?

A

GLN uses HCO3 and ATP to make carbamoyl aspartate (carbamoyl phosphate synthetase 2)

+PRPP
-UTP

  • Cytosol and mito
  • too much carbamoyl aspartate: orotic aciduria
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13
Q

What is phase 2 of pyrimidine synthesis?

A

Orotate attached to PRPP to become UMP, OMP is in rxn too

UMP synthetase

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14
Q

What is phase 3 of pyrimidine synthesis?

A

UMP made into dCTP and DTTP

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15
Q

Regulatory steps of pyrimidine synthesis?

A

Carbamoyl Synthetase:

  • Inhibited to UMP/UTP
  • stimulated by PRPP

ATCase:
-stopped by CTP

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16
Q

Pentose phosphate pathway?

A

produces rp5 and nadph

uses nadph to maintain reducing environment
makes Gluthione

17
Q

What is the significance of methotrexate?

A

prevents oxidation of NADPH

Targets DHFR, cant make folate into tetrahydrofolate

disrupts DNA replication

18
Q

What do sulfa drugs too?

A

disrupt DNA synthesis in bacteria

inhibits enzyme that puts paba into folate

19
Q

What does depriving cells of GMP and dGTP do?

A

conversion of IMP to XMP

inhibits IMP dehydrogenase

Deprives them of adequate supplies of GMP, dGTP

disrupting this helps prevent rejection

20
Q

What is purine catabolism?

A

Ribose is removed from guanosine and inosine, makes guanine and hypoxanthine

converges at xanthine formation

converted to uric acid

21
Q

what is ADA, what does it do?

A

hydrolytic deamination, adenosine to inosine

overproduction makes anemia

underproduction leads to scid

22
Q

xantine oxidase? what does it do?

A

hypoxantine to xantine to uric acid

target for gout

23
Q

oxidation levels of purines, explain it

A

become more and more oxidized, uric acid is most oxidized

24
Q

What is SCID and how does it happen?

A

B and T cells compromised

Due to ADA deficiency , high levels of adenosine which is converted to dATP, blocks formation of other dNDPs, impairs DNA synthesis

25
Q

what is gout?

A

Overproduction of uric acid, under excretion of uric acid

Deposits of sodium urate

Due to xanthine oxidase, treatment inhibits this

uric acid is a marker for gout

26
Q

How are pyramidines catabolized?

A

uracil/cytosine becomes malonyl CoA

thymine becomes methylmalonyl coA or succinyl coA

27
Q

What is the salvage pathway used for and how?

A

nucleotides which are recovered can be reused for purines

APRT: makes AMP
HGPRT: makes GMP or IMP

28
Q

what is Lesch-Nyhan

A

Defects in HGPRT of purine salvage pathway

self mutiliation!!

Excess purines

Severity depends on HGPRT excess

29
Q

What does Acyclovir do?

A

acyclovir gets phosphorylated by Thymidine kinase at higher rate than cellular kinase

becomes acyclovir dGTP, incorporated into dividing viral cells, used to help heal sores

“false nucleotide, blocks dna synthesis

MCM Quiz 1 (9 decks)

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