nucleotide metabolism (20)

Question 1

what are the 4 purines?

Answer 1

adeninin
guanine
hypoxanthine
xanthine

Question 2

what are the 3 pyrimidines?

Answer 2

uracil
thymine
cytosine

Question 3

list the 2 sources of ribose 5 phosphate

Answer 3

• glucose metabolism, pentose phosphate shunt

- nucleoside degradation generates ribose-1-phosphate (which can be converted to R5P)

Question 4

what two compounds are needed to synthesize PRPP? what is the enzyme?

Answer 4

ATP and ribose 5 phosphate

enzyme: PRPP synthase

Question 5

list the 3 things that PRPP is required for

Answer 5

1. De novo synthesis of pyrimidine & purine nucleotides
2. The salvage pathways for purine nucleotides
3. The biosynthesis of nucleotide coenzymes NAD and FAD

Question 6

is this statement describing purines or pyramide synthesis?

the ring is built on a molecule of PPRP

Answer 6

purines

Question 7

list the precursors for the purine ring

Answer 7

glutamine, glycine, CO2, aspartate and two 1 carbon fragments from the 1 carbon folate pool

Question 8

how many high energy phosphate bonds are needed for the synethsis of IMP?

Answer 8

6

Question 9

what step in IMP synthesis is considered the rate limiting and regulated step?

Answer 9

the 1st step

Question 10

how many steps in IMP synthesis require folate?

Answer 10

2

Question 11

how many steps in IMP synthesis can be blocked by azaserine?

Answer 11

2

Question 12

what is azaserine an analog of?

Answer 12

glutamine

Question 13

what does azaserine block?

Answer 13

the amide transfer from glutamine

Question 14

what are sulfonamides an alalog of?

Answer 14

p-aminobenzoic acid

Question 15

what do sulfonamides block?

Answer 15

the biosynthesisi of folic acid- so blocks nucleotide synthesis

Question 16

how is de novo synthesis of purine nucleotides regulated?

Answer 16

feedback inhibition

Question 17

what 3 compounds block the enzymes PRPP synthetase and PPRP amidotransferase? (enzymes that catalyze the 1st two steps of IMP synethsis)

Answer 17

IMP, GMP, AMP

Question 18

what is the function of HGRT?

Answer 18

catalyzes the formation of nucleotides from either hypoxanthine or guanine. This enzyme is inhibited by IMP and GMP

Question 19

what is the function of ARPT?

Answer 19

catalyzes the formation of AMP from adenine- inhibited by AMP

Question 20

is this statement describing purines or pyrimidines?

the ring is formed THEN it reacts with PRPP to form the nucleotide

Answer 20

pyrimidines

Question 21

what are the 2 precursors to the pyramidine ring?

Answer 21

carbamoylphosphate & asparate

Question 22

what do patients with OTC deficiencies build up high levels of pyrimidines in their serum & urine

Answer 22

because in OTC carbamoyl phosphate builds up and this is a precursor for the synthesis of pyramidines

Question 23

what is orotic aciduria?

Answer 23

genetic disorder of pyrmidine biosynthesis

Question 24

how can orotic aciduria be alleviated?

Answer 24

by feeding of uridine or cytidine→this supplies the body with the needed pyrimidine bases and inhibits CP II

Question 25

what is substrate channeling?

Answer 25

when 1 enzyme passes its product right off to the next to use as a substrate

Question 26

list the 6 enzymes that are inhibited by azaserine

Answer 26

* CPSII * CTP synthase * FGAR aminotransferase * GMP synthase * PRPP aminotransferase * Aorargine synethase

Question 27

when are deoxynucleotides made?

Answer 27

during DNA replication

Question 28

what drug inhibits ribonucleotide reductase?

Answer 28

hydroxyurea

Question 29

what is the enzyme ribonucleotide reductase needed for?

Answer 29

in the formation of deoxynucleotides

Question 30

what reaction does thymidylate synthase catalyze? what form of THF is needed for this rxn?

Answer 30

dUMP--> dTMP | N5N10 methyleneTHF

Question 31

how is THF regenerated after the pathway that forms deoxyribonucleotides?

Answer 31

the enzyme dihydrofolate reductase which requires NADPH

Question 32

what drug inhibits dihydrofolate reductase? thereby inhibiting the regeneration of THF

Answer 32

methotrexate

Question 33

what is the function of 5-fluorouracil?

Answer 33

blocks the transfer of the methylene group to the pyrimidine ring

Question 34

what are the 2 ways that AMP can be degraded?

Answer 34

1. Can first be deaminated to IMP→ then hydrolyzed to inosine 2. Or can be hydrolyzed to adenosine then demaminated to inosine

Question 35

how is GMP degraded?

Answer 35

it is hydrolyzed to guanosine

Question 36

how is CMP degraded?

Answer 36

can be deaminated to UMP and then hydrolyzed to uridine-or it can be hydrolyzed to cytidine and then deaminated the uridine

Question 37

what is the final product of purine degradation?

Answer 37

uric acid

Question 38

what is the enzyme xanthine oxidase

Answer 38

``` enzyme required for breakdown of AMP and the oxidation to uric acid contains molybdenum (only known function in the human body of this element) ```

Question 39

what is the final product of pyrimidine degradation?

Answer 39

uracil: B-alanine thymine: B- aminoisobutyrate

Question 40

what is the cause of gout?

Answer 40

caused by precipitation of sodium urate crystals in the joints & kidneys

Question 41

what are the 2 circumstances that can cause gout?

Answer 41

1. abnormal PRPP synthetase and not responsive to feedback inhibition 2. HGPRT deficiency leads to increased PRPP levels (so greater de novo synthesis of purines)

Question 42

what is the treatment for gout?

Answer 42

allopurinol (which blocks the production of uric acid)

Question 43

what is lesch nyhan syndrome?

Answer 43

X linked recessive condition due to severe or complete deficiency of HGPRT

Question 44

what are the symptoms of lesch nyhan syndrome?

Answer 44

Hyperuricemia, gout, urinary tract stones and neurological symptoms (mental retardation, spasticity and self mutilation)

Question 45

what is the treatment for lesch nyhan sydrome?

Answer 45

can use allopurinol to reduce the uric acid formation but it does NOT alleviate the neuro symptoms Can also be treated with: low protein diet, cochicine and a low purine diet

Question 46

what is the cause of adenosine deaminase deficiency?

Answer 46

deoxyadenosine & adenosine are abundant and are not degraded but are efficiently converted to nucleotides in white blood cells High levels of dATP inhibit ribonucleotide reductase which inhibits DNA synethsis- so the WBCs

Question 47

what is the treatment for adensoine deaminase deficiency?

Answer 47

bone marrow transplantation & enzyme replacement therapy | Gene therapy has been experimented