Purine and Pyramidine Metabolism

Question 1

Sources of atoms for purine de novo synthesis

Answer 1

aspartate, glycine, glutamine, CO2 and N10-formyltetrahydrofolate
THEN the purine base is built directly on the ribose sugar

Question 2

Purine synth starts with?

Answer 2

Starts with ribose-5-phosphate from HMP shunt

Question 3

PRPP synth materials and inhib/acivate?

Answer 3

requires: 5-phosphate, ATP, and PRPP synthatase enzyme
inhib: purine ribonucleotides (end product inhib)
activate: inorganic phosphate

Question 4

RLS and KEY regulated step in Purine synth

Answer 4

PRPP + glutamine –> 5’-phosphoribosylamine
Enzyme: glutamine phosphoribosyl pyrophosphate amidotransferase
Activated by: PRPP
Inhib by: (end products) AMP, GMP, IMP

Question 5

IMP formation and conversion

Answer 5

9 steps after RLS (needs 4 ATP)
IMP can be converted to AMP or GMP (end product inhibited)
Then AMP and GMP converted to ATP and GTP (both use ATP)

Question 6

Sources of atoms for pyrimidine de novo synthesis

Answer 6

Glutamine, aspartate, CO2, N10-formyltetrahydrofolate

Question 7

Pyrimidine RLS and key reg step

Answer 7

2ATP + CO2 + glutamine –> CP

enzyme: CPS2
inhib: UTP
acitvate: ATP

Question 8

Pyrimidine degradation key step?

Answer 8

NONE!

Question 9

Purine degradation key step?

Answer 9

key enzymes: adenosine deaminase (adenosine --> inosine)
xantinie oxidase (xanthine --> uric acid)

Question 10

2 diffs between purine and pyrimidine synth

Answer 10

1) purine: build the base ONTO the ribose sugar
pyrimidine: build the base separately then attach to ribose sugar
2) purine: IMP made first then converted to AMP and GMP
pyrimidine: UMP is the initial product, then converted to UTP, which is then converted to CTP
AND dTTP is only made after UMP converted to dUMP

Question 11

Enzyme that reduce ribose to deoxyribose

Answer 11

ribonucleotide reductase
two regulatory sites
activated by ATP
inhib by dATP

Question 12

Gout: enzyme defic

Answer 12

PRPP synthetase gene mutations can increase expression of the enzyme, thus greater purine production, ultimately increasing purine degradation to uric acid

Question 13

SCID enzyme defic

Answer 13

adenoside deaminase defic (ADA)
usually converts adenosine to inosine in purine degradation
defic leads to dATP buildup in blood which inhibs ribonucleotide reductase –> leads to dNTP defic, ends up stopping immune system cells from dividing

Question 14

Lesch Nyan defic (pathway?)

Answer 14

purine salvage pathway (increase in PRPP, more synthesis of purines) - gout, self-mutilation, severe mental disorders

Question 15

Methotrexate and 5-fluorouracil mechs?

Answer 15

inhibit nucleotide synth by inhibiting BH4 (required for purine synth, and TMP from dUMP)