Neucleotide Metabolism Flashcards
Difference between nucleoside vs. nucleotide? Tell me about purines vs pyrimidines?
Side: B + S
Tide: B + S + P
A gang(2 rings ) is pure
Name (5) functions of Nucleotides in the body?
DNA/RNA ATP/GTP Parts of Co-Enzymes UDP - Activators cAMP - Physiological mediators
Three sources of Nucletotides?
De Novo Synthesis
Diet (5%)
Salvage
______ enzymes break ______ into ____, and ____. ______ are readily absorbed by the small intestines. ______ however ______ by intestinal mucosa. are broken down by
Pancreatic,
Nucleotide
bases and sugars,
Bases (purines/pyrimidines)
Name the 4 components necessary for purine synthesis?
AA: glycine (body) Glutamine Asparate - amino doners
THF - add 2 carbons from AA
Funct. Enzyme: 1-Tri, 2-Bi, 3-Mon
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?
IMP (5 ATP)
AMP, GMP (6 ATP)
R5P –1–> PRPP –2–> IMP ==3,4==» GMP & AMP
1) PRPP synthase
2) glutamine phosphoribosyl amidotransferase
3) Inosine (IMP) Dehyrogenase
4) AMP synthase
Describe the RLS of purine synthesis? What are the NEG regulators of 3,4 steps?
R5P –1–> PRPP –2–> IMP ==3,4==» GMP & AMP
Glutamine phosphoribosyl amidotransferase
(+) PRPP
(-) IMP, *GMP, *AMP
What is PRPP? name and molecular significance?
*phosphoribosyl pryrophosphate
activated 5RP
What drugs inhibit steps 2, and 3? What are the targets?
R5P –1–> PRPP –2–> IMP ==3,4==» GMP & AMP
2) Methotrexate (THF)
3) Mycophenolic acid (IMP Dehydrogenase) (WBC - stops division)
IMP or Adenosine (purine) is broken down to _____, then ______ where it is acted upon by _____, producing ______
inosine hypoxanthine xanthine oxidase (2x bi-functional) Uric acid Uric acid
Guanine (purine) is broken down to _____, where it is acted upon by _____, producing ______
xanthine
xanthine oxidase (1x) (bifunctional)
Uric acid
Uric acid is very ______ and can ______.
Name the drug that inhibits Xanthine Oxidase? What patients would we give this drug? Why?
insoluble, precipitate
Uric acid buildup/problem w/excretion. The body secretes, hypoxathine or xanthine when degrading adenosine, and guanine respectively
Treatments for Uric Acid Buildup
Colchicine - inhibits inflammation not uric acid levels
Uricosuric Drugs - (+) secretion
Allopurinol - Inhibits xanthine ox.
The salvage pathway turns what to what?
Name the enzymes that do this? reactant? what bases?
Bases, that were to be excreted to NT.
APRTase - adenine + PRPP
HGPRTase - Hypoxanthine & Guanine + PRPP
What caused Lesch Nyhan Syndrome?
HGPRTase deficiency - Little to no salvage
X-linked recessive
MegaLBST Anemia - continuous synthesis uses up all the folate to produce RBC.
Name the 4 components necessary for pyrimidine synthesis?
AA: Glutamine (amino), Asparate (3C + Amino)
THF - add 1 carbons from COz
Funct. Enzyme: 1-Tri, 2-Bi, 3-Mon
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?
UMP (3 ATP)
UTP (5ATP)
CTP (6 ATP)
UMP –> UTP -> CTP
Glutamine + COz –1–> Carbomyl Phosphate –> orotate –2–> UMP
NOTE: UMP + ((PP)) = UTP
UTP –3–> CTP
1) Carbamoyl phosphate synthase II (CPSII, cytosol) - Part of ring
2) UMP Synthase (2 functions) add R5P, and form UMP
3) CTP synthase
What is the rate limiting step in pyrimidine synthesis? Regulators
1) Carbamoyl phosphate synthase II (CPSII, cytosol) - Part of ring
(+) ATP
(-) UMP
Cause, Consequence and Treatment for Orotic Aciduria?
Defect in UMP synthase (2 funct)
Increased orotic acid -insoluable.
acid urine, orange crystals
Uridine (helps reverse process)
RNA and DNA pyrimindes includes? Pyrimidine degredation results in ___, ____; Cytidine becomes _____ which then becomes ____; these product can have their ____ opened resulting in ____, ______
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
Pyrimidine Salvage
Uracil/Cyto(sine) –> (dine)
Thy(mine) –> (midine)
Nucleosides –> Nucleotides
Ribose 1 Phosphate
Deoxybose-1-Phosphate
Nucleoside Kinase
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)
Ribonucleotide Reductase
DNA Synthesis:
Because dUDP is not used to make DNA is has to be converted to dTTP using
thymidylate synthase
What drug inhibits Ribonucleotide Reductase? Thymidylate Synthase?
Methotrexate
Hyroxyurea - Stop DNA
5-Fluorouracil
Stops purine/pyrimidine synthesis
(anti-tumor agents)
