Nucleotide Metabolism Flashcards
Nucleoside is composed of what 2 things?
Nucleotide is composed of what 2 things?
Nitrogenous base + sugar
Nucleoside + 1-3 phosphate groups
What makes ATP/GTP high energy bonds that are able to drive many biochemical reactions
The anhydride bonds linking the 2nd and 3rd phosphate on a nucleoside triphosphate
First step in purine nucleotide synthesis
Ribose-5-phosphate gets converted to PRPP by PRPP synthetase
Where is the ribose-5-phosphate come from?
HMP shunt (well fed state)
- Activator of PRPP synthetase?
2. Inhibitor?
- Inorganic phosphate
2. Purine ribonucleotides
Where is the pyrophosphate attached?
What else will be attached here?
The first carbon
Nitrogenous base
Purine synthesis is the default production of ___; in order to make ___, other steps with be taken
Ribonucleotides; deoxyribonucleotides
Rate limiting step of purine nucleotide synthesis
PRPP amidotransferase
What is the purpose of folate in purine nucleotide synthesis
Folate is required as a carbon donor
What is the form in which folate is used?
What is required to make this form/what does it do
THF (tetrahydrofolate)
Dihydrofolate reductase/ it is the enzyme that converts dihydrofolate to trihydrofolate (THF)
- PRPP amidotransferse is activated by?
2. Inhibited by?
- PRPP (substrate)
2. Purine nucleotides (end products)(IMP, AMP, and GMP) and 6-mercaptopurine
What drug inhibits dihydrofolate reductase?
What type of analog is it?
Only works on what type of cells?
Methotrexate (an anti-tumor drug)
Folic acid analog
Mammalian
Sulfonamides:
- Structural analogs of ?
- Competitive inhibitor of?
- Only works in
- What type of drugs are sulfa drugs
- PABA (para-aminobenzoic acid)
- Bacterial purine synthesis/production of folic acid
- Bacteria (because humans get folate from their diet)
- Antibiotics
- PYRIMIDINE nucleotide synthesis- what is the rate limiting enzyme
- Activated by
- Inhibited by
- Where in the cell is the enzyme located
- CPS II (carbamoyl phosphate synthetase II)
- PRPP
- UTP (end product)
- Cytoplasm
Which is higher, production of pyramidines or purines?
Production of pyramidines because they are smaller
What provides the pentose for pyrimindine needed for synthesis?
PRPP - pyrimidine bases are produced then attached to PRPP
Function of ribonucleotide reductase
What drug inhibits this enzyme?
What else does this drug treat? How?
Converts ribonucleotides to deoxyribonucleotides
Hydroxyurea (anti-tumor drug)
Sickle cell anemia; increases the synthesis of fetal hemoglobin
Additional steps to convert dUMP to dTMP use which enzyme?
This enzyme is inhibited by?
Thymidylate synthase
5-fluorouracil (5-FU)
Hydroxyurea and 5-FU affect production of?
What is significant about this?
Affects the production of DNA but not RNA
Those drugs are good at targeting rapidly dividing cells
Thymidylate synthase requires?
Folate in the form of THF
What does the drug trimethoprim do?
Antibiotic that inhibits the prokaryotic version of dihydrofolate reductase (eukaryotic version is inhibited by methotrexate)
Purine salvage pathway:
Nitrogenous base is recovered after removing phosphate and sugar moieties yielding what 2 things?
Hypoxanthine or guanine
- What is one of the causes severe combined immunodeficiency disease (SCID)
- What 2 cells are particularly affected by this deficiency
- What does SCID cause for its patients?
- Treatment
- Whats significant about SCID clinically?
- Adenosine deaminase deficiency
- T-cells and B-cells
- Requires them to live in a sterile bubble
- Bone marrow transplant or enzyme replacement
- First successful gene therapy trial
After recovery of the nitrogenous base in the degradation/salvage pathway, what 2 things can happen to the base?
The base can be shuttled back into purine synthesis or degraded to uric acid
Excretion pathway uses which intermediate and which enzyme to produce uric acid?
Intermediate xanthine and the enzyme xanthine oxidase
- What is a result of hyperuricemia?
- Causes accumulation of?
- 3 things that under-excretion of uric acid can be caused by?
- Gout
- Uric acid crystals in the joints
- Poor kidney function, acid-base imbalance, and certain drugs (anti-tumor drugs)
2 things that cause gout
What body part can gout affect besides joints
Under excretion of uric acid (most common) or overproduction of uric acid
The eye
What drug is used if you over produce uric acid? What does it inhibit
Allopurinol - inhibits xanthine oxidase (which produces uric acid)
Lesch-Nyhan syndrome
- Deficiency in?
- Caused by defect in?
- Results in extreme, why?
- Symptoms
- Purine salvage pathway/purines
- Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
- Hyperuricemia because purine degradation products are forced into uric acid production since they cannot do pathway
- Severe mental retardation and self destructive behavior/self-mutilation
