Exam 3 Nucleotide Metabolism (DNA)

Question 1

dNTPs synthesis overview:

Answer 1

take any rNDP, reduce it (ie removed -OH) to make dNDPs then add phosphate to made dNTPs

Question 2

what is the enzyme that will reduce ribose into deoxyribose

Answer 2

ribonucleotide reductase

Question 3

how does ribonucleotide reductase perform redox rxn

Answer 3

creates free radicals eg catalytic Tyr free radical

Question 4

why is ribonucleotide reductase not picky

Answer 4

this one enzyme acts on all NDPs and can act on NTPs

Question 5

NADPH provides

Answer 5

the necessary e-s for redox rxns

Question 6

ribonucleotide reductase makes

Answer 6

dNDPs

Question 7

how many regulation sites are on ribonucleotide reductase

Answer 7

3; 1 catalytic site and 2 allosteric sites

Question 8

what promotes function in allosteric site in ribonucleotide reductase

Answer 8

ATP

Question 9

what turns off function in allosteric site in ribonucleotide reductase

Answer 9

dATP

Question 10

the allosteric site preference for activity is called what in ribonucleotide reductase

Answer 10

specificity site; it is a volume dial ie regulates exact amount of activity

Question 11

what do kinases do in deoxyribonucleotide synthesis

Answer 11

all the dNDPs are converted to dNTPs

Question 12

why is dTTP special

Answer 12

it makes a detour in making dTTP from UDP

Question 13

what are the ways to make dUMP for dTTP synthesis

Answer 13

1. remove PPi (pyrophosphate) from dUTP

2. deamination of dCMP

Question 14

to make T (thymine) in deoxy, need extra _ group

Answer 14

methyl

Question 15

what adds a methyl to dUMP to create dTMP

Answer 15

thymidylate synthase

Question 16

what is the methyl donor in dTMP synthesis

Answer 16

B9/methyl-THF

Question 17

what is the clinical relevance of 5-FU?

Answer 17

it makes an unusable substrate for thymidylate synthase (it is a suicide inhibitor) which stops T pathway synthesis

Question 18

how do we regenerate THF?

Answer 18

NADPH used for reduction of dihydrofolate (DHF)

Question 19

what do the two drugs that competitively inhibits dihydrofolate reductase accomplish? drug names are methotrexate and trimethoprim

Answer 19

inhibit ability to incorporate T in DNA (good for cancer)

Question 20

how does endonucleases work

Answer 20

“inside” cut in the middle

Question 21

how does exonucleases work

Answer 21

“outside” chew from the end

Question 22

endonucleases make

Answer 22

oligonucleotides

Question 23

exonucleases make

Answer 23

nucleoside monophosphates; NMPs (mononucleotides)

Question 24

pyrmidines use _ and _ to interconvert between nucleobases and NMPs in 2 steps

Answer 24

phosphorylases and kinases

Question 25

have nucleoside but use phosphorylase, what are we making

Answer 25

removing sugar so making nucleobases from nucleosides (breakdown pathway)

Question 26

have nucleoside but use kinases, what are we making

Answer 26

adding a phosphate; makes NMPs ie convert nucleosides into nucleotides (salvage pathway)

Question 27

nucleotidases work to remove

Answer 27

phosphate to make nucleosides from nucleotides

Question 28

thymidine kinase 1 works to

Answer 28

make thymidine (nucleoside) into dTMP (nucleotide)

Question 29

why is viral thymidine kinase not as discriminating as human thymidine kinase, and what is the benefit of this?

Answer 29

viral thymidine will accept purines as well as T's. The benefit is that make a drug (acyclovir) will not interact with human thymidine kinase so it will terminate synthesis of T's in viral DNA

Question 30

purines use _ to interconvert between nucleobases and NMPs in one step

Answer 30

phosphoribosyltransferases

Question 31

phosphoribosyltransferases do what?

Answer 31

remove phosphate (interchange between nucleobases and NMPs)

Question 32

adenine phosphoribosyltransferases makes:

Answer 32

AMP

Question 33

HGPRT makes:

Answer 33

IMP/GMP

Question 34

hypoxanthine is the precursor for

Answer 34

IMP (purines)

Question 35

nitrogenous bases can be broken down into (2)

Answer 35

1. uric acid | 2. B-ureidopropionic acid

Question 36

uric acid is the final product of

Answer 36

purine catabolismm

Question 37

B-ureidopropionic acid is the final product of

Answer 37

pyrmidine catabolism

Question 38

uric acid like glutathione is an _

Answer 38

antioxidant

Question 39

T/F: uric acid/urate is soluble

Answer 39

FALSE insoluble

Question 40

how does gout occur?

Answer 40

uric acid crystals collecting in joints

Question 41

what is one pathology for gout

Answer 41

HPRT deficiency; cannot salvage nucleobases of purines

Question 42

how does SCID occur?

Answer 42

deficiency of adenosine deaminase; breakdown is not functional. dAMP into dATP is inhibited and dAMP accumulates. Inhibition of ribonucleotide reductase so foward rxn and thus no DNA synthesis