Nucleotide Biosynthesis and Salvage (Watts)

Question 1

what are some nucleotide functions? (3)

Answer 1

energy metabolism (ATP),
enzyme cofactors (NAD+),
signal transduction (cAMP)

Question 2

what are some nucleic acid functions?

Answer 2

storage of genetic info (DNA), transmission of genetic info (mRNA), processing of genetic info (ribozymes), protein synthesis (tRNa/rRNA)

Question 3

what is a nucleotide?

Answer 3

• nitrogeneous base
• sugar (pentose)
• phosphate group

nucleoside just base and sugar, no phosphate group

Question 4

typically, where is the phosphate group attached? (carbon number)

what charge?

Answer 4

5’, negatively charged

Question 5

in nucleotides, how it the pentose ring attached to the nucleobase?

Answer 5

beta N-glycosidic bond,

Question 6

how can nucleotides be synthesize from amino acids, ribose-5-p, CO2, and NH3?

Answer 6

De novo.

Question 7

what can nucleotides be salvaged from?

Answer 7

nucleobases

Question 8

what do many parasites lack, causing them to rely on salvage nucleotide biosynthesis?

Answer 8

lack de nevo biosynthesis..

anti anti-parasite drugs inhibit salvage pathways

Question 9

does the de novo pathway use free bases?

Answer 9

no,

with de novo pathway a purine base is built up atom by atom directly onto ribose structure..

while pyrimidines base is assembled first then attached to ribose

Question 10

what are the two pathways of nucleotide biosynthesis?

Answer 10

de novo and salvage

Question 11

with de novo purine synthesis, is the base made before attachment to ribose or during?

Answer 11

purine is made WHILE attached to ribose…

this is different from de novo synthesis of pyrimidines because those are made first then attached to ribose.

Question 12

de novo biosynthesis of purines begin with what?

Answer 12

synthesis of PRPP= 5-phosphoribosyl-1-pyrophosphate with Glu

Question 13

what is the first intermediate of de novo biosynthesis of purines ?

Answer 13

inosinate (IMP)

Question 14

what two bases are synthesized from the intermediate inosinate?

Answer 14

adenine and guanine (purines)

Question 15

what are the four allosteric regulators of de novo purine synthesis?

Answer 15

1. IMP, AMP, and GMP which are products of glutamine-PRPP amidotransferase rxn
2. excess GMP, which inhibits formation of xanthylate from inosinate by IMP dehydrogenase rxn
3. GTP, limits conversion of IMP to AMP, and ATP limits conversion of IMP to GMP
4. ADP and GDP, PRPP synthesis inhibited by these

Question 16

Inosinate can form ___ or ___?

Answer 16

AMP or GMP

Question 17

what is the intermediate of inosinate (IMP) to AMP?

Answer 17

adenylosuccinate,

IMP –> adenylosuccinate
via adenylosuccinate synthase and GTP

Question 18

what is the intermediate of inosinate to GMP?

Answer 18

Xanthylate (XMP)

IMP–> XMP
via IMP dehydrogenase

then XMP–> GMP
via XMP-Glutamine amidotransferase + ATP, and GLn

Question 19

Pyrimidines are made from what three things during de novo synthesis?

Answer 19

Asp, PRPP, and carbamoyl phosphate,

remember, with pyrimidines de novo synthesis, you make the pyrimidines FIRST, then attach to ribose-5-p

Question 20

what is the first committed step of the pyrimidine de novo synthesis?

Answer 20

Asp + N-carbamoylphosphate,

via aspartate transcarbamoylase (ATCase)

Question 21

some anticancer drugs target?

Answer 21

thymidylate synthase,

which catalyzes dUMP–>dTMP

Question 22

what is the allosteric inhibitor of pyrimidine de novo synthesis?

Answer 22

ATCase is inhibited by its end-prods= CTP

accelerated by ATP

Question 23

dUMP can be converted to dTMP via?

Answer 23

thymidylate synthase

Question 24

if you have a deficiency in folic acid, what will be results?

Answer 24

causes decrease in thymidylate synthesis, (normally catalyzes UTP–>TMP)

so without folic acid, you have Uracil being incorporated into DNA, can cause cancer, heart disease, neurological impairment

Question 25

what are the precursors of deoxyribonucleotides?

what catalyzes this rxn?

Answer 25

ribonucleotides!

ribonucleotide ruductase, reduces 2’ C-OH –> 2’ -H

uses NADPH thioredoxin or glutaredoxin

Question 26

when free bases released in metabolism are reused it is called what ?
what organ is especially dependent on this?

Answer 26

salvage pathway

brain

Question 27

during catabolism of purine, what do they form?

Answer 27

uric acid

Question 28

Gout can be associated with excess ____ ____?

Answer 28

uric acid.

Question 29

during catabolism of pyrimidines, it forms ___, then urea.

Answer 29

NH4+, then urea.

can produce CAC intermediates

Question 30

both adenine and guanine are derived from __, which is the first compound in the pathway to form purine rings.

Answer 30

IMP, inosine monophosphate

Question 31

a key regulatory step in the synthesis of purines is the production of _____ .

(What must be formed before we can start building purines ?)

Answer 31

5-phospho-alpha-D-ribosyl 1 - pyrophosphate (PRPP)

catalyzed by PRPP synthetase.