Nucleotide Metabolism Flashcards
Name all of the purines
Adenine and Guanine
Name all of the Pyrimidines
Cytosine, Thymine, Uracil
These high energy bonds link the 2nd and 3rd phosphate on a nucleoside triphosphate and drive many biochemical reactions
Anhydride bonds
Ribose-5 Phosphate is derived from the _______ pathway.
HMP Shunt
List the (+) and (-) regulators of PRPP synthetase.
(+) Activator = Inorganic Phosphate
(-) Inhibitor = Purine ribonucleotides
PRPP has a pyrophosphate and a nitrogenous base attached at the _______.
Primary Carbon(1’)
The rate limiting step in Purine nucleotide synthesis is catalyzed by _______.
PRPP Amidotransferase
In Purine nucleotide synthesis, _______, ________, & ________ become part of the nitrogenous base in subsequent steps.
Glycine, Aspartate, and glutamine
In Purine nucleotide synthesis, _____ is required for subsequent steps as a carbon donor.
Folate
______ is required to make THF, the form in which folate is used.
Dihydrofolate reductase
This drug will inhibit PRPP Amidotransferase similar to the inhibition by high levels of downstream products.
6-Mercaptopurine (Purine Analog)
_____, a folic acid analog, is a common anti-tumor drug that inhibits _____, ultimately inhibiting nucleotide biosynthesis and rapidly dividing cells (common among anti-tumor drugs). It works especially in ________ cells.
Methotrexate, dihydrofolate reductase, mammalian.
Sulfa drugs function as ________.
Antibiotics
This family of drugs are:
Structural analogs of PABA
Competitive inhibitors of folic acid production in bacteria
Inhibitors of bacterial purine synthesis
(Think bacteria drugs)
Sulfonamides
This is the rate limiting, committed step in pyrimidine synthesis…
CPS II - carbamoyl phosphate synthetase II
What are the regulators of CPS II?
Activated (PRPP)
Inhibited (UTP)
In pyrimidine synthesis, where is CPS II located in the cell?
Cytosol
Once pyrimidine bases are produced, where are they attached?
To PRPP
Ribonucleotides can be converted into deoxyribonucleotides by ___________
Ribonucleotide reductase
______ is an anti-tumor drug that inhibits Ribonucleotide reductase.
(Also used to treat Sickle Cell Anemia as it promotes HbF synthesis)
Hydroxyurea
Additional steps to convert dUMP into dTMP use _________.
Thymidylate synthase.
Thymidylate synthase is inhibited an anti-tumor drug known as….
5-fluorouracil (5-FU)
Hydroxyurea and 5-FU will affect ______ production, but not _________ production, so are especially good at targeting rapidly dividing cells.
1) DNA
2) RNA
This class of antibiotic is selective for the prokaryotic version of dihydrofolate reductase.
Trimethoprim
Humans must acquire _____ in the diet, whereas prokaryotes can synthesize their own.
(Hint: the usable form in humans is THF)
Folate
Nucleotide Metabolism:
This condition results in patients being susceptible to almost any microorganism, requiring living in a sterile environment and is attributed to a deficiency in _________ in ____% of cases
SCID : severe combined immunodeficiency disease (the condition)
Adenosine deaminase deficiency
14% of cases
In SCID, these 2 cell types of the immune system are majorly affected…
T-cells & B-cells
The excretion pathway uses this intermediate ________, and this enzyme_______, which produces Uric acid, which is excreted in the _______.
Xanthine
Xanthine oxidase
Urine
An accumulated amount of nucleotides may indicate a problem with the ______ cycle, which could potentially lead to the development of ______.
Excretion, gout
This condition is indicative of elevated levels of Uric Acid in the blood…
Hyperuricemia
Gout can be caused by:
Underexcretion of _______ (most common)
Which can be caused by poor _____ function, _______ imbalance, and certain drugs, etc.
Uric acid
Kidney, acid-base
In over-producers of uric acid, this drug inhibits xanthine oxidase which produces uric acid.
Allopurinol
This deficiency is X-linked and affects the purine salvage pathway. Caused by a defect in HGPRT and deficit of purines.
Lesch-Nyhan syndrome
Hydroxyurea will inhibit the production of _________ ________.
Ribonucleotide reductase
_______will inhibit the conversion of dUMP to dTMP which is used to RNA and DNA.
5-FU (5-fluorouracil)
_________ bases are more complex to synthesize and so therefore about ____% of them are salvaged in the salvage pathway and ____% are excreted.
Purine
90%
10%
______ _________ , which is responsible for the overproduction of uric acid, is the enzyme effected by allopurinol.
Xanthine oxidase
