Neucleotide Metabolism

Question 1

Difference between nucleoside vs. nucleotide? Tell me about purines vs pyrimidines?

Answer 1

Side: B + S
Tide: B + S + P

A gang(2 rings ) is pure

Question 2

Name (5) functions of Nucleotides in the body?

Answer 2

DNA/RNA
ATP/GTP
Parts of Co-Enzymes 
UDP - Activators 
cAMP - Physiological mediators

Question 3

Three sources of Nucletotides?

Answer 3

De Novo Synthesis
Diet (5%)
Salvage

Question 4

______ enzymes break ______ into ____, and ____. ______ are readily absorbed by the small intestines. ______ however ______ by intestinal mucosa. are broken down by

Answer 4

Pancreatic,
Nucleotide
bases and sugars,
Bases (purines/pyrimidines)

Question 5

Name the 4 components necessary for purine synthesis?

Answer 5

AA: glycine (body) Glutamine Asparate - amino doners
THF - add 2 carbons from AA
Funct. Enzyme: 1-Tri, 2-Bi, 3-Mon

Question 6

Name the first intermediate of purine synthesis? This gives rise to (branch point)? How much ATP is used to make it? to make a purine?

Answer 6

IMP (5 ATP)

AMP, GMP (6 ATP)

Question 7

R5P –1–> PRPP –2–> IMP ==3,4==» GMP & AMP

Answer 7

1) PRPP synthase
2) glutamine phosphoribosyl amidotransferase
3) Inosine (IMP) Dehyrogenase
4) AMP synthase

Question 8

Describe the RLS of purine synthesis? What are the NEG regulators of 3,4 steps?

R5P –1–> PRPP –2–> IMP ==3,4==» GMP & AMP

Answer 8

Glutamine phosphoribosyl amidotransferase

(+) PRPP
(-) IMP, *GMP, *AMP

Question 9

What is PRPP? name and molecular significance?

Answer 9

*phosphoribosyl pryrophosphate

activated 5RP

Question 10

What drugs inhibit steps 2, and 3? What are the targets?

R5P –1–> PRPP –2–> IMP ==3,4==» GMP & AMP

Answer 10

2) Methotrexate (THF)

3) Mycophenolic acid (IMP Dehydrogenase) (WBC - stops division)

Question 11

IMP or Adenosine (purine) is broken down to _____, then ______ where it is acted upon by _____, producing ______

Answer 11

inosine
hypoxanthine
xanthine oxidase (2x bi-functional)
Uric acid 
Uric acid

Question 12

Guanine (purine) is broken down to _____, where it is acted upon by _____, producing ______

Answer 12

xanthine
xanthine oxidase (1x) (bifunctional)
Uric acid

Question 13

Uric acid is very ______ and can ______.

Name the drug that inhibits Xanthine Oxidase? What patients would we give this drug? Why?

Answer 13

insoluble, precipitate
Uric acid buildup/problem w/excretion. The body secretes, hypoxathine or xanthine when degrading adenosine, and guanine respectively

Question 14

Treatments for Uric Acid Buildup

Answer 14

Colchicine - inhibits inflammation not uric acid levels

Uricosuric Drugs - (+) secretion

Allopurinol - Inhibits xanthine ox.

Question 15

The salvage pathway turns what to what?

Name the enzymes that do this? reactant? what bases?

Answer 15

Bases, that were to be excreted to NT.

APRTase - adenine + PRPP
HGPRTase - Hypoxanthine & Guanine + PRPP

Question 16

What caused Lesch Nyhan Syndrome?

Answer 16

HGPRTase deficiency - Little to no salvage

X-linked recessive

MegaLBST Anemia - continuous synthesis uses up all the folate to produce RBC.

Question 17

Name the 4 components necessary for pyrimidine synthesis?

Answer 17

AA: Glutamine (amino), Asparate (3C + Amino)
THF - add 1 carbons from COz
Funct. Enzyme: 1-Tri, 2-Bi, 3-Mon

Question 18

Name the first intermediate of pyrimidine synthesis? This gives rise to (branch point)? How much ATP is used to make it? to make a purine?

Answer 18

UMP (3 ATP)
UTP (5ATP)
CTP (6 ATP)

UMP –> UTP -> CTP

Question 19

Glutamine + COz –1–> Carbomyl Phosphate –> orotate –2–> UMP

NOTE: UMP + ((PP)) = UTP
UTP –3–> CTP

Answer 19

1) Carbamoyl phosphate synthase II (CPSII, cytosol) - Part of ring
2) UMP Synthase (2 functions) add R5P, and form UMP
3) CTP synthase

Question 20

What is the rate limiting step in pyrimidine synthesis? Regulators

Answer 20

1) Carbamoyl phosphate synthase II (CPSII, cytosol) - Part of ring

(+) ATP
(-) UMP

Question 21

Cause, Consequence and Treatment for Orotic Aciduria?

Answer 21

Defect in UMP synthase (2 funct)
Increased orotic acid -insoluable.

acid urine, orange crystals

Uridine (helps reverse process)

Question 22

RNA and DNA pyrimindes includes? Pyrimidine degredation results in ___, ____; Cytidine becomes _____ which then becomes ____; these product can have their ____ opened resulting in ____, ______

Answer 22

Cytosine; **Thymine & **Uracil
uridine, uracil (by De-amination)
rings

U - B-alanine
T - B-aminoisobutryric acid (levels are high after chemo - only way of production) tells cell death.

+NH2 and CO2

Question 23

Pyrimidine Salvage

Uracil/Cyto(sine) –> (dine)
Thy(mine) –> (midine)
Nucleosides –> Nucleotides

Answer 23

Ribose 1 Phosphate
Deoxybose-1-Phosphate
Nucleoside Kinase

Question 24

DNA Synthesis:

The starting material is ribonucleosides 5’ diphosphates (ADP, GDP, CDP, UDP) what is the name of the enzyme that gives rise to the deoxyversion (dADP, etc)

Answer 24

Ribonucleotide Reductase

Question 25

DNA Synthesis:

Because dUDP is not used to make DNA is has to be converted to dTTP using

Answer 25

thymidylate synthase

Question 26

What drug inhibits Ribonucleotide Reductase? Thymidylate Synthase?
Methotrexate

Answer 26

Hyroxyurea - Stop DNA
5-Fluorouracil
Stops purine/pyrimidine synthesis
(anti-tumor agents)