Purines and pyrimadines

Question 1

what do we need to make purines

Answer 1

THF
GLYCINE (major difference)
ASPARTATE
Glutamine

Question 2

what do we need purines for ?

Answer 2

energy carrier molecules
SAM
DNA synthesis

Question 3

what are the precursor molecules for purines and pyrimides

Answer 3

purines: IMP - the first purine

pyrimidines; OMP - the first pyrimidie

Question 4

what is the commited step for purine synthesis

Answer 4

The enzyme glutamin prpp amindotransferase

Question 5

what are the steps after formation of 5 phosophoriboysul 1 amine

Answer 5

1. Glycine +atp
2. N-formyl THF - THF
3. Glutmine +ATP
4. ATP
5. CO2
6. Aspartate+ATP
7. Fumerate (leaving)
8. Nformyl THF
9. removal of water
   IMP

Question 6

draw the pathway from IMP TO AMP AND GMP and name the 4 enzymes involved

Answer 6

1. To form AMP
   - adenylosuccinate synthetase (GTP)
   - adenylosuccinate lyase (removes fumerate)
2. To form GMP
   - IMP DH (nad, h20)
   - XMP- Glutamine amidotransferase (atp)

Question 7

where does the breakdown and synthesis of purines occure

Answer 7

breakdown: extrahepatic tissues

synthesis : liver

Question 8

where does the breakdown and synthesis of purines occur

Answer 8

breakdown: extrahepatic tissues

synthesis : liver

Question 9

describe the salvage pathway of purines

Answer 9

AMP- ADENOSINE- INOSINE-HYPOXANTHINE ( 2 paths)
1.gout 2. recycling goes to IMP then back to AMP

GMP-guanosine-guanine - GMP ( vie HGPRT)

Question 10

Describe process of forming deoxyribose

Answer 10

happens at the nucleotide diphosphate level , the enzyme is ribonucleotide reductase which has thioreduxin as a cofactor (sh) that gets oxidised. but needs to be replaced to keep the cycle going so another enzyme thioreduxin reductase which uses NADPH .

same example with glutathione

Question 11

regulation of ribonucleotide reductase

Answer 11

quite complex as enzyme has 2 allosteric sites

ATP- bound to active site (activates)
dATP (deactivates)

starts of with the pyrimides (C+U)
C: CDP-dCDP - dCTP—–dna synthesis
U: UDP-dUDP-dUMP-dTMP-dTDP-dTTP- dna synthesis

the dttp goes and binds to regulatory site and now activates the purines
GDP-dGDP-dGTP-dna
ADP-dADP-dATP-dna (inactives enzyme)

Question 12

what enzyme abnormailites can cause goat/podogra

Answer 12

1. HGPRT
2. PRPP sytnthesase ( cos usually its negatively controleed by adp and gdp but in variant forms can lead to an overproduction of purines)

Question 13

Lesch-Nyan synchdrome

Answer 13

mental retardation, purine salvage aint working , hyerourecemia
X LINKED
self mutalation
disorder of nervous sytem

Question 14

clincial aspects of purine metabolism

Answer 14

usually results from abnormal purine break down

HGPRT -complet lack = lesh nyan syndrome
HGPRT- partial defect- GOUT
ADA- complet defct - SCID
Glucose 6 phosphatase - von Gierkes disease - hyperurecemia
Xanthine oxidase- xanthinuria - hypourecima - renal lithiasis (stones)

APRT- renal lithiasis

MANY DEFCTECT IN PRPP SYNTHESTASE

1. over active because of elevated vmax
2. does not respond to feedback loop
3. no feedback loop produced
4. has an increased affinity for substrate (ribose 5 phosphate)

Question 15

origin of pyrimidine ring

Answer 15

1. majority (aspartate)
2. glutamate
3. co2

Question 16

name the products and enzymes of de novo synthesis of pyrimidines

Answer 16

1. Carbomoyl phopsphate
2. ATtcase gives us carbomoyl aspartate
3. dihydrorotase gives us DHOA
4. dihydroorat DH gives us orotic acid
5. orotate phosphribosyl transferase gives us OMP
6. Orotodylic acid decarboxylase

Question 17

what are the products that can be formed from UMP

Answer 17

UMP-UDP-dUDP-dUMP-dTMP-dTDP-dTTP

OR

UMP——2 kinases——UTP—atp + glutamine -CTP

Question 18

thymidylate synthase

Answer 18

coverts DUMP —-dTMP
highly regulated
requires THF to work

Question 19

Thymidylate synthase

Answer 19

coverts DUMP —-dTMP
highly regulated
requires THF to work

Question 20

how do we regenerate THF after it has been used

Answer 20

THF gets turned into DHF which then gets coverted back by dihydrofolate reductase w which uses NADPH

Question 21

regulation of Atcase

Answer 21

:) ATP

;( CTP

Question 22

Which pathways uses the slavage pathway more and why?

Answer 22

purine- about 90~% compared to 30% of pyrimide this is because in pyrimidine we have low numbers of ribose 1 phosphate and deoxy ribose 1 phosphate

Question 23

thymidine kinase

Answer 23

enzyme that adds ATP to thymidine to give you dTMP. It is allosterically inhibited by dTTP. Activity of TK is closely related to the proliferative state of the cell. TK activity tises dramatically as celll enters S phase

Question 24

what other products aprart from the slavage pathay can pyrimides form, step by step

Answer 24

Catbabolism:

cytosine - deaminated - uracil - b alanine- acetyl coa

thymine - b aminoisobutyrate- succinyl co A

products are excreted in urine or are converted to water and co2 and Nh3

Question 25

clinical aspects of pyrimidines

Answer 25

UMP synthase is made up of the last 2 enzymes

1. orotate phosphoribosyl transferase
2. OMP decarboxylase

orotic aciduria type 1 : deficiency of both

orotic aciduria type 1: deficiency of last enzyme

symptoms:

• retarded growth
• leukopenia
• severe anemia

treatment: oral intake of uridine or cytidine because then they will be convertred to UMP by the acition of kinase

Mild orotic aciduria:
increases levels of CP which increases pyrimidine synthesis

deficiency of Vitamin B12 and folic acid
-deficiency of dTMP

Question 26

which type of THF is used to give a methyl group to dUMP

Answer 26

methylenetetrahydrofolate