Biosynthesis and Degradation of Nucleotides part 2

Question 1

Altering phosphorylation states alters ?

Answer 1

enzyme usage

Question 2

Ribonucleotide Reductase

Answer 2

will reduce ribose to deoxyribose
only accepts diphosphate

Question 3

Ribonucleotide Reductase Process

Answer 3

1. 3’ ribonucleotide radical forms
2. 2’ hydroxyl is protonated
3. Water is eliminated to form a radical stabilized carbocation
4. Dithiol is oxidized on the enzyme; two electrons are transferred to the 2’ carbon
5. step 1 is reversed, regenerating a tyrosyl radical on the enzyme
6. the enzyme dithiol is reduced to complete the cycle

Question 4

RNA to DNA conversion

Answer 4

1. reduction of the 3’ carbon to form a radical
2. protonation of the 2’
3. loss of water to form 2’ carbocation (radically stabilized)
4. oxidation of the dithiol, transfer of 2 electrons to the 2’ carbon
5. radical. is transferred back to tyrosine
6. dna nucleotide (dNDP) is released and enzyme is reset

Question 5

How is ribonucleotide reductase regulated?

Answer 5

overall activity (energy) and substrate specificity
(balance of nucleotides )

Question 6

What does degradation of purines make?

Answer 6

uric acid

Question 7

What does degradation of pyrimidines make?

Answer 7

urea, which is cleaved to ammonia, CO2 and amine

Question 8

Which are usually salvaged and reduced: Pyrimidines or Purines?

Answer 8

Purines

Question 9

Which are evenly split between salvage and degradation: Pyrimidines or Purines?

Answer 9

pyrimidines

Question 10

What does degradation of nucleotides provide?

Answer 10

multiple drug targets

Question 11

Adenosine Degradation process

Answer 11

1. 5’ nucleotidase- removes phosphate from sugars
2. adenosine deaminase- oxidative deamination to make inosine
3. nucleosidase- cuts base from sugar
4. xanthine oxidase- oxidizes hypoxanthine-> xanthine
5. Xanthine oxidation- oxidized xanthine -> uric acid

Question 12

Guanosine Degradation process

Answer 12

1. 5’ nucleotidase- removes phosphate
2. nucleosidase- removes sugar
3. guanine deaminase- forms xanthine
4. xanthine oxidase- forms uric acid

Question 13

What can we block xanthine oxidase to treat?

Answer 13

gout

Question 14

Adenosine and PRPP makes?

Answer 14

AMP and deoxyribose with the enzyme adenosine phosphoribosyltransferase

Question 15

Guanosine and PRPP make

Answer 15

GMP with the enzyme hypoxanthine-guanine phosphoribosyltransferase

Question 16

Hypoxanthine and PRPP make?

Answer 16

IMP with the enzyme hypoxanthine-guanine phosphoribosyltransferase

Question 17

Thymine Degradation process

Answer 17

1. dihydrouracil dehydrogenase- reduces alkene
2. dihydropyrimidinase- hydrolyze the amide bond
3. beta-ureidopropionase- hydrolyze urea
4. aminotransferase- takes nitrogen
5. methylmalonyl semialdhyde is converted to succinylCoA

Question 18

Uracil Degradation Process

Answer 18

1. Dihydrouracil dehydrogenase reduces the alkene
2. Dihydropyrimidinase hydrolizes the amide to open the ring
3. beta-ureidopropionase- hydrolyze the urea
4. aminotransferase- takes N
5. Malonyl semialdehyde is converted to AcetylCoA

Question 19

What relies on pyrimidine salvage?

Answer 19

Bacteria and parasites

Question 20

Plasmodium Falciparum

Answer 20

malaria parasite
relies exclusively on pyrimidine salvage

Question 21

Things that rely on pyrimidine salvage are good for?

Answer 21

Drug Targets

Question 22

Diseases related to purine & pyrimidine salvage

Answer 22

Lesch-Nyhan Syndrome
Gout
Purine Autism
Epilepsy

Question 23

Gout

Answer 23

deficit in purine salvage
leads to an incr in uric acid
treated with Allopurinol- a xanthine oxidase inhibitor

Question 24

Some Purine Autism and Epilepsy forms are linked to defects in?

Answer 24

metabolism