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BioChem Exam 3 > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

1
Q

purine and pyrimidines

A

purines = 2 rings
adenine, guanine

pyrim = 1 ring
cytosine, urasil, thymine

nucleoside + Pi = nucleotide

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2
Q

important precursor for all nucleotides

A

PRPP

ATP+ribose-5-Pi —-> PRPP+AMP

via PRPP synthetase

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3
Q

pyrimidine-related enzymes to know

A 
CPSII
ATCase
dihydroorotase
dihydroorotase dehydrogenase
UMP synthetase
nucleoside mono-Pi kinase
nucleoside di-Pi kinase
CTP synthetase
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4
Q

purine related enzymes to know

A

purinosome

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5
Q

purine synthesis

A

branch off from IMP

  1. AMP
    - –uses GTP for nrg
    - –replaces carbonyl w/ NH3
    - –inhibited by AMP
  2. GMP
    - –uses ATP
    - –redox w/ H2O to make 2nd carbonyl
    - –replaces it w/ NH3
    - –inhibited by GMP
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6
Q

deoxyribonucleotide synthesis overview

A

converting ribose to deoxyribose requires reduction rxn

deoxyribonucleotides are created from their respective NDPs

**pyrimidines take a detour

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7
Q

ribonucleotide reductase

A

1 enzyme acts on all NDPs and NTPs

NADPH provides e-for redox

regulation

  • -active site = catalytic site
  • -allosteric sites = specificity site and activity site
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8
Q

salvage

A
  1. pyrimidines use phosphorylases and kinases for salvage in 2 steps
  2. purines use phosphoribosyltransferases to salvage in 1 step

**know thymidine kinase and HPRT

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9
Q

catabolism

A

nitrogenous bases can be broken down

–uric acid is the final product of purine catabolism

–B-ureidopropionic acid can be converted to alanine + CO2 + NH3 by ureidopropionase
to complete pyrimidine catabolism

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10
Q

what enzymes are deficient for the following genetic medical conditions?

  1. megaloblastic anemia
  2. gout
  3. lesch-nyhan syndrome
  4. SCID
A
  1. UMP synthetase
  2. HPRT
  3. HPRT
  4. adenosine deaminase
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11
Q

CPSII

A

carbamoyl pi synthetase II

has a channel
starts w/ bicarbonate
ends w/ carbamoyl Pi

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12
Q

ATCase

A

aspartate transcarbamoylase

has 2 allosteric regulators

  1. ATP activates
  2. CTP inhibits
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13
Q

dihydroorotase

A

closes the ring
–reverse of a hydrolase

carbamoylasparate to dihydroorotate

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14
Q

dihydroorotate dehydrogenase

A

located in mito

dihydroorotate to orotate

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15
Q

UMP synthetase

A

multifunctional protein

  1. removes PPi when orotate added to PRPP
  2. decarboxylates orotate to form uracil
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16
Q

megaloblastic anemia

A

occurs when cells fail to divide

B9 or B12 deficiencies

but fails to respond to vit B treatment because of a deficiency in UMP synthetase

17
Q

NMP kinase

A

transforming UMP to UTP

UMP+ATP = UDP + ADP

uracil

18
Q

NDP kinase

A

transforming XMP = XTP

XDP + YTP = XTP + YDP

also used in transforming UMP to UTP (uracil) but this enzyme has broad specificity

19
Q

CTP synthetase

A

CTP or cytosine is the only nucleotide to be synthesized directly as a triphosphate

CTP synthetase has 2 allosteric regulators
1. GTP activates
2. CTP inhibits
(same as ATCase)

20
Q

purines - rxns 1-3

A

form the 5 membered ring

  1. swaps PPi on PRPP for NH3 from Gln
  2. adds glycine
  3. adds formyl group to complete ring
21
Q

purines - rxns 4-10

A

form the 6 membered ring

  1. adds NH3 from Gln to start 2nd ring
  2. closes the 5C ring
  3. adds CO2 from HCO3 first to Gln then to Gly
  4. adds Asp to carboxyl
  5. release fumarate
  6. 2nd formyl group added to complete the 6C ring

closure forms hypoxanthine

22
Q

purinosome

A

purines are made in purinosome

6 enzymes do 10 rxns
—rxns carried out on proteins
2 additional enzymes provide formyl groups
—proximity regulates flow

23
Q

thymidylate synthase

A

adds methyl to dUMP to create dTMP

24
Q

pyrimidine salvage

A

nucleobases to nucleosides
—nucleoside phosphorylase

nucleoside to nucleoside mono-Pi
—nucleoside kinase

pyrimidine salvage takes 2 steps

  1. phosphorylase makes nucleoside
  2. kinases make nucleotides
25
Q

thymidine kinase

A

accepts purines and T

to form acyclovir ?
acyclovir tri-Pi can be incorporated into viral DNA

26
Q

purine salvage

A

use phosphoribosyltransferases to salvage in one step

nuclobases to nucleoside mono-Pi
—-phosphoribosyltransferase

27
Q

HPRT

A

makes IMP or GMP

guanine + PRPP = GMP + PPi

hypoxanthine + PRPP = IMP + PPi

28
Q

nitrogenous base catabolism

A

uric acid is final product of purine catabolism

B-ureidopropionic acid is converted to alanine in pyrimidine catabolism

29
Q

ureidopropionase

A

used to complete pyrimidine catabolism

converts B-ureidopropionic acid to alanine

30
Q

gout

A

high conc of uric acid causes it to crystalize

caused by HPRT deficiency
—also causes lesch-nyhan syndrome

31
Q

SCID

A

severe combined immunodeficiency disease

deficient in adenosine deaminase

w/o this enzyme dAMP accumulates

resulting in deoxyribonucleotides not being produced
DNA cannot be synthesized
cells do not divide

BioChem Exam 3 (10 decks)

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