2 Purine and Pyrimidine Metabolism

Question 1

what are the requirements of creating IMP?

Answer 1

PRPP (via ribose5p and PRPP synthetase) + Glycine + 6 ATP over 11 steps = IMP

Question 2

what are secondary sources for IMP?

Answer 2

adenine and guanine

Question 3

how is IMP converted to AMP and GMP?

Answer 3

IMP+ATP = GMP, IMP+GTP=AMP

Question 4

how is the mechanism of AMP and GMP regulated?

Answer 4

all phosphorylated end products feedback to several steps in the formation of IMP

Question 5

How is the ratio of gmp to amp maintained?

Answer 5

by requiring the opposite end product in the synthesis process

Question 6

what is the purpose of purine salvage?

Answer 6

allows free bases, nucleosides and nucleotides to be exchanged as needed

Question 7

<p>

| what does adenosine kinase do in purine salvage</p>

Answer 7

<p>
it is the only mechanism to convert an adenosine nucleoside into a AMP nucleotide with the use of an ATP in the body</p>

Question 8

what causes lesch nyhan syndrome and what is the symptoms

Answer 8

loss of HGPRT builds up free bases hypoxanthine and guanine which will cause them to be shunted to uric acid. This can cause gout and self mutilation (finger biting)

Question 9

what problems can adenosine deaminase def cause and why?

Answer 9

inhibits adenosin to inosine xversion thus inhibits purine salvage in B/T lymphocytes which is the only source. this causes ADA-SCID (bubble boy syndrome)

Question 10

What is the net reaction mechanism for pyrimidine synthesis?

Answer 10

carbamoyl phosphate (via CO2+glutamine+2ATP) + aspartate(via aspartate transcarbamoylase) then several steps make orotate -> OMP -> UMP

Question 11

What is the regulation of pyrimidine synth?

Answer 11

CPSII is activated by PRPP and inhibited by UTP(neg feedback)

Question 12

what are the steps of pyrimidine salvage?

Answer 12

freebases can become nucleosides (via nucleoside phosphorylase) and nucleosides can become nucleotides (via nucleoside kinase) then both steps can be reversed by nucleoside phosphatases

Question 13

how is N-ribose converted to N-deoxyribose?

Answer 13

NDP will be converted by ribonucleotide reductase and energy from thioredoxin-SH

Question 14

how is the spent thioredoxin-S regenerated?

Answer 14

thioredoxin reductase will use NADPH to regenerate thioredoxin-S to thioredoxin-SH

Question 15

what can a deficiency or excess in dNTP cause?

Answer 15

deficiency is lethal and excess causes mutations

Question 16

what are purines degraded into

Answer 16

excess purines not salvaged will degrade into their free base form then into xanthine then into uric acid

Question 17

what does excess uric acid cause and what can treat it?

Answer 17

excess uric acid causes gout and allopurinol can inhibit the enzymes converting hypoxanthine and xanthine (both xanthine oxidases)

Question 18

what are the two reasons of uric acid excess

Answer 18

90% is lack of excretion 10% overproduction

Question 19

What type of parasites would HGPRT inhibitors affect?

Answer 19

Parasites that purine salvage

Question 20

How can the etymology of gout be differentiated?

Answer 20

radiolabeled glycine will differentiate

Question 21

What enzymes may be deficient in orotic aciduria?

Answer 21

orotate phosphoribosyl transferase and orotidine 5’-decarboxylase

Question 22

how is orotate aciduria treated?

Answer 22

oral uridine

Question 23

what will excess carbamoyl phosphate shunt to?

Answer 23

pyrimidine synthesis

Question 24

what else can cause orotic aciduria?

Answer 24

OTC deficiency of the urea acid cycle