nucleotide metabolism

Question 1

what composes the purine ring?

Answer 1

3 aa- aspartate, glycine and glutamine
N10-formyl-THF
CO2

Question 2

what is the regulated step in purine do novo synthesis?

Answer 2

formation of PRPP by PRPP synthetase

Question 3

what is the committed step in purine de novo synthesis?

Answer 3

formation of 5-phosphoribosyl-1-amine by amid-phosphoribosyl transferase

Question 4

where is the “branch point”?

Answer 4

IMP

Question 5

what regulates PRPP synthetase?

Answer 5

(-) by ADP and GDP

Question 6

what regulates amino-transferase?

Answer 6

(+) PRPP

(-) AM/D/TP, GM/D/TP

Question 7

what is the product of purine metabolism?

Answer 7

uric acid

Question 8

where does most de novo purine synthesis occur?

Answer 8

liver, most other tissues use salvage pathway

Question 9

what are the starting points for the salvage pathway of purine synthesis?

Answer 9

hypoxanthine, guanine, adenine

Question 10

what is the class of enzymes used in salvage pathway?

Answer 10

HGPRTase (phosphoribosyltransferases)

Question 11

where is the salvage pathway especially important?

Answer 11

brain

Question 12

what is the significance of the purine nucleotide cycle?

Answer 12

important in exercising muscle, allows for the replenishment of fumarate

Question 13

what is ADA?

Answer 13

adenosine deaminase deficiency, leads to accumulation of adenosine = increased dATP = decreased activity of ribonucleoside reductase = decreased DNA synthesis; assoc with impaired immunity- SCID

Question 14

what is gout?

Answer 14

high concentrations of uric acid
related to decreased salvage pathway and increased de novo synthesis, leading to increased uric acid. treat with colchicine, allopurinol

Question 15

MOA of allopurinol

Answer 15

inhibits xanthine oxidase

Question 16

lesch-nyhan syndrome

Answer 16

loss of HGPRT gene = dec salvage pathway = CNS effects and severe gout

Question 17

what s the committed step in pyrimidine synthesis?

Answer 17

formation of carbamoyl phosphate by CPS II

Question 18

what is the main intermediate in pyrimidine synthesis?

Answer 18

Orotate

Question 19

how is orotate converted to UMP?

Answer 19

using UMP synthetase (2 domains)

Question 20

what is the precursor for all pyrimidines?

Answer 20

UMP

Question 21

how is UMP converted to CTP

Answer 21

first UMP –> UDP –> UTP

then UTP –> CTP by CTP synthase

Question 22

what is ribonucelotide reductase?

Answer 22

enzyme that is responsible for the production of deoxy-nucleotides

Question 23

what is used to reduce nucleotides to deoxy forms?

Answer 23

thioredoxin

Question 24

MOA of hydroxyurea

Answer 24

inhibits nucleotide reduction by ribonucleotide reductase = dec deoxynucleotides = decreased DNA and cell cycle arrest

Question 25

how is ribonucleotide reductase regulated?

Answer 25

(+) ATP, (-) dATP

allosteric regulation by dTTP, dGTP, dATP

Question 26

how s dTMP formed?

Answer 26

dUMP –> dTMP by thymidylate synthase, uses N5,N10-methylene-THF as methyl donor

Question 27

MOA of 5-FU

Answer 27

inhibits thymidylate synthase

Question 28

how is de novo synthesis of pyridimines controlled?

Answer 28

CPS II

Question 29

what enzyme is used in pyrmidine catabolism?

Answer 29

dihydropyrimidine dehydrogenase (DPD)- caalyzes reduction of U and T, involved in degradation of chemo meds as well, like 5-FU

Question 30

catabolism of CMP and UMP =

Answer 30

B-alanine –> malonyl-CoA –> FA synthesis

Question 31

catabolism of dTMP =

Answer 31

aminoisobutyrate –> methyl-malonyl-CoA –> sucinyl-Coa –> TCA cycle

Question 32

consequence of UMP synthase deficiency

Answer 32

UMP synthase is responsible for the formation of UMP from orotate, if deficient, orotate will accumulate

Question 33

salvage pathway for dTTP

Answer 33

= dUMP, by thymidine kinase

Question 34

Salvage pathway for uracil

Answer 34

= UMP, by uradine phosphorylase, uridine kinase

Question 35

salvage pathway for deoxycytosine

Answer 35

= dCMP, by deoxycytosine kinase