14- Purine and Pyrimidine Metabolism

Question 1

What is produced form HMP shunt?

Answer 1

NADPH and ribose5P

Question 2

PRPP synthetase

Answer 2

takes ribose-5-P > Phosphoribosyl pyrophosphate (PRPP)

PRPP used in De Nova synthesis or Salvage Pathways

Question 3

PRPP amidotransferase

Answer 3

PRPP > 5-Phosporibosylamine

Inhibitted by:
IMP, GMP, and AMP (all downstream products)

Question 4

How much nucleotide synthesis will be happening in a cell in Go?

Answer 4

Minimally, Go will not be preparing to divide so they will not need nucleotides.

Question 5

What happens with overactive PRPP synthetase?

Answer 5

overproduction of nucleotides

gout and kidney stones

Question 6

What is IMP?

Answer 6

just upstream of AMP and GMP

P group, ribose and base (hypoxanthine)

Question 7

What does Allopurinol and Azathioprine target and why?

Answer 7

PRPP amidotransferase

Cancer cells need lots of nucleotides, inhibition will stop purine and replication

Allopurinol- treat gout
– purine nucleotide analog that inhibits PRPP amidotransferase

Azathioprine- treats leukemia (immunosupressant)
– also inhibits PRPP amidotransferase

Question 8

Purine synthesis pathway

Answer 8

starts with ribose5P > PRPP synthetase > PRPP > PrPP amidotransferase > 5 phosporibosylamine

Question 9

Pyrimidine synthesis pathway

Answer 9

Starts with pyrimidine then the ribose

CPS2: Carbamoyl phosphate synthetase 2
CO2 + glutamine +ATP > carbamoyl phosphate&raquo_space;>DHF

Dyhydroflorate reductase:
DHF > THF

Question 10

Which cells have CPS2 enzyme?

Answer 10

All cells except RBC

Question 11

What forms gout?

What enzyme is targeted to help?

Answer 11

orotic acid build up (orotic aciduria)

Treatment: drugs target dyhydroflorate reductase

Question 12

two sources of orotic aciduria?

Answer 12

Defective OTC (urea cycle, liver): carbamoyl P builds up > cytoplasm > picked up in pyrimidine pathway > excess orotic acid

Defective PRPP: which is enzyme after OA is made. (Pyrimidine pathway) OA builds up cause it’s not processed.

Question 13

OTC or PRPP enzyme deficiency?

Answer 13

OTC deficiency: orotic aciduria and hyperammonemia

• • OTC is in urea cycle, everything backs up, NH3 build up
• • also decrease BUN and increse OA = OTC deficiency

PRPP: only orotic acid build up, no ammonia in blood.

Question 14

Cancer drugs target which enzymes to inhibit dTMP?

Answer 14

dTMP is used to make DNA

1. Hydroxy urea inhibits ribonucleotide reductase (baso cell carcinoma)
2. 5-Fluorouracil inhibits thymidylate synthase (baso cell carcinoma)
3. Methotrexate inhibits dihydrofolate reductase (DHFR) (anti tumor drug)
4. Trimethoprim inhibits DHFR (anti microbial)
5. Pyrimethamine inhibits DHFR (anti protozoal)

Inhibit normal and cancer cells.

Question 15

Purine Salvage pathway

Answer 15

AMP > Adenine > adenosine + adenosine deaminase > inosine > hypoxanthine
– Adenosine deamination:
Adenosine > inosine

GMP > guanosine > Guanine

once hypoxanthine and guanine are formed they can go to salvage (90%) or excretion pathways (10%) as uric acid

Question 16

Why are purines are salvaged?

Answer 16

it takes energy to make it so we like to keep using it.

Question 17

Adenosine Deaminase deficiency

Answer 17

severe immunodeficiency

autosomal recessive disease

Question 18

What is allopurinol used for?

Answer 18

Inhibits Xanthine oxidase

Xanthine –x> uric acid
— uric acid is not water soluble, builds up in joints, gout

helps treat gout

Question 19

Cholchicine

Answer 19

No effect on xanthine oxidase (uric acid production)

Colchicine acts on inflammation. Reduce severity?

lactic acid competes with uric acid for excretion. Tell patients not to exercise– less gout

Question 20

what is HGPRT?

Answer 20

enzyme that takes purines back to salvage

Question 21

HGPRT deficiency

Answer 21

Can’t salvage as much so more will go to excretion.

Usually Young children!

More uric acid is built up. upstream enzymes not inhibited so more xanthine produced –> more uric acid
– normally purine nucleotides (AMP, IMP GMP) inhibit amidotransferase

Cause Lesch-Nyhan disease
symptoms:
- spastic cerebral palsy
-self-mutilation 
-hyperuricemia
-early death

Question 22

Why is gout the rich mans disease?

Answer 22

High protein food is usually expensive.

Gout formed by uric acid, product of N pathways.