Nucleotide Metabolism Flashcards
What are nucleotides made out of?
(3)
- Nitrogenous base
- Pentose monosaccharide
- 1-3 phosphate groups
What are the 2 Purines?
Adenine and Guanine
For both DNA/RNA
What are the 3 pyrimidines?
Thymine, Cytosine, Uracil
Uracil-RNA
Thymine-DNA
What are the 2 common bases involved in purine metabolism?
- Hypoxanthine formation of Inosine monophosphate (IMP)
- Xanthine found in xanthosine MP
What is a nucleoside?
Addition of pentose sugar to a base
Addition of ribose sugar to bases A, G, C, T and U produce what?
Adenosine
Guanosine
Cytidine
Thymidine
Uridine
Addition of 1-3 phosphate group to a nucleoside yields what structure?
Nucleotide (mono, di, tri)
Phosphate groups are responsible for the negative charges w/ RNA/DNA
What is used to synthesize PRPP?
5-Phosphoribosyl-1-pyrophosphate
Ribose 5-phosphate from the HMP (non-oxidative)
Used for both purine/pyrimidine pathways
Is PRPP an activated or deactivated pentose?
Activated
PRPP synthetase is an X-linked enzyme. T/F?
Activation/Inhibition?
TRUE-from mother
* Activated by inorganic phsophate
* Inhibited by purine ribonucleotides
Where does De Novo Purine synthesis occur?
CYTOPLASM
What are the five precursors involved in purine de novo synthesis?
- CO2
- Aspartate
- Glycine
- Glutamine
- Folic Acid (Formyl tetrahydrofolate)
What is the RLS in De novo Purine Synthesis?
Construction of the purine ring
Do humans synthesize folic acid?
NO-thats why sulfa drugs do not interfere with humans and only the bacteria.
De Novo Purine Synthesis Pathway
Simplified
- PRPP
- IMP
- AMP/GMP
Conversion of Nucleoside Monophosphates to di and triphosphates
INSERT PIC
Purine Salvage 2 enzymes involved
- HGPRT (Hypoxanthine-guanine phosphoribosyltransferase)
- APRT(Adenine phosphoribosyltransferase)
Lesch-Nyhan Syndrome
- X-linked recessive disorder
- Due to deficiency of HGPRT
- Results in an increased breakdown of purines causing elevated levels of uric acid
Are purine rings easily cleaved in humans?
NO-not cleaved at all. Purine nucleotides are degraded primarily in the **liver **and the free bases are sent out and salvaged by peripheral tissues
What is the cause of Gout?
Purine undersecretion OR overproduction
Immunodeficiencies include:
1. Adenosine deaminase deficiency
2. Purine nucleoside phosphorylase deficiency
In Pyrimidine Synthesis are rings formed before or after the attachment to the ribose-5-phosphate of PRPP?
Before and put on in 1 piece
What is the RLS in pyrimidine synthesis?
2 ATP + CO2 + Glutamine–> Carbamoyl phosphate
Enzyme is Carbamoyl Phosphate Synthetase II (CPS II)
Are folic acid derivatives used in Pyrimidine synthesis?
NO
1. Aspartic acid
2. Amide of glutamine
3. CO2
Are Pyrmidine bases highly soluble?
Yes-less clinically significant than purine salvage
What is the common disorder of Pyrmidine Metabolism?
Orotic Aciduria
1. Poor growth
2. Megaloblastic anemia
The reduction of ADP, CDP, UDP to dADP, dCDP, dUDP is catalyzed by what enzyme?
Ribonucleotide diphosphate reductase
Inhibitors: dATP, hydroxyurea
Where does the digestion of dietary Nucleic Acids take place?
Occurs in the small intestine
* End product is Uric Acid
What does Sulfonamides do?
Competitive inhibitors of the enzyme dihydropteroate synthetase that only efects bacteria
What is an anti metabolite?
Similar to normal body molecules (slightly different structure)
* Stop cancer cells from making and repairing DNA that they need to grow and multiply
