Metabolism of nucleotides

Question 1

only ___% nucleosides absorbed is reutilized for nucleic acid synth, ___% of these used by rapidly regenerating ____

Answer 1

5; 25; enterocytes

Question 2

how are ribo and deoxyribo different?

Answer 2

2’ OH (ribo) or H (deoxy)

Question 3

functions of nucleotides?

Answer 3

precursors for DNA and RNA, ATP, adenine nucleotides for 3 major coenzymes (FAD, NAD, CoA), activated intermediates (UDP=gluc), regulators (cAMP)

Question 4

2 types of pathways?

Answer 4

de novo, salvage

Question 5

precursors for de novo?

Answer 5

Asp, CO2, Gly, Gln, formate, R5P

Question 6

what is PRPP?

Answer 6

phosphoribosylpyrophosphate

Question 7

inosate has base ___, ___ as nucleotide

Answer 7

hypoxanthine; inosine

Question 8

what is IMP?

Answer 8

first purine made in de novo, Inosine monophosphate

Question 9

inhibitors of purine nucleotide biosynth?

Answer 9

purine-containing nucleotides

Question 10

this condition is characterized by high blood lvls of uric acid due to overproduction or underexcretion of uric acid

Answer 10

gout

Question 11

symptoms of gout?

Answer 11

pain/inflammation of joints (uric acid crystal deposits)

Question 12

treatment of gout?

Answer 12

suicide inhibitors (allopurinol), excretion stimulants, diet/alcohol restriction

Question 13

beer is rich in ___

Answer 13

purines

Question 14

what is a suicide inhibitor?

Answer 14

bind permanently to active site (no substrate turnover)–>enzyme out of commission

Question 15

condition due to deficiency in HGPRT activity due to gene mutation (X linked)

Answer 15

Lesch Nyhan syndrome

Question 16

why is de novo synth ^ by Lesch Nyhan?

Answer 16

PRPP ^ –> IMP/GMP drop –> more substrate for Gln-PRPP amidotransferase, less inhibition by end products –>^ de novo

Question 17

symptoms of Lesch-Nyhan?

Answer 17

neurological effects (hostility, retardation, self-mutilation, motor dysfunction), gouty arthritis

Question 18

strategy for de novo pyrimidine synth?

Answer 18

1) synth carbamoyl P 2) build pyrimidine ring (orotate) 3) link ring to R5P

Question 19

what is rate limiting step of pyrimidine synth?

Answer 19

synth of carbamoyl phosphate

Question 20

how do CPS1 and CPS2 differ?

Answer 20

1 is in urea synth, 2 is in pyrimidines; 1 is in mito matrix, 2 is in cyto; 1 N donor is NH4, 2 N donor is Gln; 1 reg. effectors are N-acetylGlu and arginine, 2 reg effectors are products (inhibitors)

Question 21

enzyme for asp –> N-carbamoylaspartate

Answer 21

aspartate trans-carbamoylase

Question 22

Orotidylate–>?–>?–>?

Answer 22

UMP; UTP; CTP

Question 23

interconversion of nucleoside mono–>di/tri by this enzyme:

Answer 23

nucleoside monophosphate (specific for base)/diphosphate (nonspecific) kinase

Question 24

___ and ___ can become dTMP

Answer 24

CDP; UDP

Question 25

methylation of dUMP by:

Answer 25

THF

Question 26

this antiviral med is used to treat herpes

Answer 26

acyclovir

Question 27

how does acyclovir work?

Answer 27

herpes virus have thymidine kinase which has broad specificity; their TK and not human enzyme will phosphorylate acylovir–>no 3’OH after incorporation so it terminates viral DNA synth

Question 28

medication that is component of HIV cocktail

Answer 28

Zidovudine

Question 29

mech of action for zidovudine

Answer 29

act as thymidine analog, get incorporated into DNA and prevent further phosphodiester bond formation

Question 30

common used anti-cancer drug that inhibits thymidylate synth (suicide inhibitor)

Answer 30

5-fluorouracil

Question 31

example of inhibitor of dihydrofolate reductase (competitive inhbitor)

Answer 31

methotrexate

Question 32

methotrexate used to treat _____

Answer 32

autoimmune disorders (arthritis, eczema)