Formation of deoxyribonucleotides and nucleotide degradation

Question 1

what is the enzyme that can turn ribonucleotides into deoxyribonucleotides?

Answer 1

ribonucleotide reductase

Question 2

what substance is produced by purine degradation?

Answer 2

uric acid

Question 3

what substance is produced by pyrimidine degradation?

Answer 3

malonyl-coA

Question 4

which enzyme transfers a methyl group from deoxyUracilMonoPhosphate to form Thymine

Answer 4

thymidylate synthase

Question 5

what is R1 of the ribonucleotide reductase enzyme?

Answer 5

this and another R1 form a homodimer, and they are the regulatory site of the enzyme. They contain specificity/hexamerization (ATP)/activity site(ATP/dATP) that are called allosteric sites

Question 6

what is the R2 of the ribonucleotide reductase enzyme?

Answer 6

it is the reactive component, it contains Fe3+ ions that are used to form a thenolate radical (Tyr residue) that is used to form a side chain that is present as a cysteine side chain.

Question 7

how does DNA differ from RNA

Answer 7

1- its nucleotides have 2’-deoxyribose residues

2- it uses the base thymine instead of uracil

Question 8

when the R2 subunit has formed the thiol radical groups, what happens next?

Answer 8

the enzymes’ oxidized thioester bonds must be reduced once more. This is done by thioredoxin reductase.

Question 9

explain thioredoxin reductase?

Answer 9

it has cysteine residues, and redox active thiol groups, and a FAD prosthetic group.

Question 10

what is the terminal reducing agent in the thioredxon reaction?

Answer 10

NADPH

Question 11

what is the end product of ribonuleotide reductase

Answer 11

dNDP - Deoxy-nucleotide-di-phosphate

Question 12

to form dNTP, which enzyme is used?

Answer 12

the nucleoside diphosphate kinase

Question 13

how does dUMP form dTTP?

Answer 13

dUTP is turned into dUMP by dUTP diphosphohydrolase.
dUMP is then methylated by thymidylate synthase to form dTMP
dTMP is phosphorylated to form dTTP

Question 14

thymidylate synthase is inhibited by?

Answer 14

5-fluorodeoxyuridylate FdUMP, this is a mechanism based inhibitor or a suicide substrate. it is a useful therapeutic drug

Question 15

inhibition of DHFR (dihydrofolate reductase) is done in which therapy?

Answer 15

cancer therapy. These can be aminopterin, methotrexate, trimethoprim

Question 16

how is THF produced from DHF?

Answer 16

By DHF reductase

Question 17

how are dietary nucleic acids absorbed?

Answer 17

they are broken down into their nucleotides in the intestine by pancreatic nucleases and intestinal phosphodiesterase. Note that they can survive the acidic stomach!

Question 18

what happens to ionic nucleotides that cannot pass the membrane?

Answer 18

they are hydrolysed to their nucleosides, by nucleotidases and non specific phosphatases

Question 19

nucleosides can be further degraded into ?

Answer 19

free bases and ribose or ribose-1-phosphate, by nuclosidase and nucleoside phosphorylase

Question 20

what is the function of a nucleosidase?

Answer 20

to remove the phosphate moiety from a nucleotide to make it into a nucleoside

Question 21

what is the final action in the purine degradation pathway?

Answer 21

xanthine is converted by xanthine oxidase to uric acid

Question 22

adenosine deaminase is an alpha/beta enzyme with a zinc ion in its active site (at the C terminal), what happens if the active site is damaged?

Answer 22

these mutations specifically kill lymphocytes and severe combined immunodeficiency disease SCID. In these conditions dATP levels increase thus ribonuceotide reductase is inhibited thus DNA synthesis is stopped

Question 23

how does muscle benefit form the purine cycle?

Answer 23

it replenishes it citric acid cycle intermediates with fumarate from the purine cycle

Question 24

gout

Answer 24

HGPRT gene mutation, severe levels of uric acid, can be treated by administering allopurinol with inhibits xanthine oxidase

Question 25

read slide 30

Answer 25

for pyrimidine pathway

Question 26

xanthine oxidase rxn produces?

Answer 26

h202 as a by product

Question 27

thymidylate synthase is inhibited in cancer therapy by?

Answer 27

5- fluorodeoxyuridylate FdUMP (a suicide substrate)

Question 28

Lymphoid tissue is particularly active in ?

Answer 28

deoxyadenosine phosphorylation