Nucleotide Metabolism Flashcards
What drug inhibits synthesis of guanine nucleotides by competitively inhibiting the IMP dehydrogenase?
Mycophenolate & Ribavarin
What causes gout?
Overproduction or under-excretion of uric acid due to enzyme deficiency
How does gout differ from Lesch-Nyhan Syndrome?
Gout has many causes, one of which is a partial mutation in the Hypoxanthine-Guanine Phosphoribosyl Transferase (HGPRT) of purine salvage. Lesch-Nyhan syndrome is caused by a deficiency of HGPRT causing overproduction of purines de novo and increased uric acid. Symptoms include hyperuricemia, megaloblastic anemia, cognitive deficits, behavioral problems, and self-mutilation
The UMP synthase is a bifunctional protein with 2 catalytic domains. What molecule does the synthase synthesize and how?
Synthesizes UMP by combining Orotic Acid & PRPP
What molecule is the parent of purines?
IMP
What enzyme is responsible for GDP/GTP synthesis from IMP?
IMP dehydrogenase
What is the mechanism of action of Sulfonamides?
Inhibit folate synthesis to prevent synthesis of purines and thymidine
What is the committed step of purine synthesis?
Amidophosphoribosyl transferase
What step in pyrimidine synthesis is rate limiting? How is the step regulated?
Synthesis of carbamoyl phosphate by the Carbamoyl Phosphate Synthetase II. The enzyme is activated by ATP & PRPP and inhibited by UDP/UTP.
What is Fluorouracil? What is its function?
Pyrimidine analog that inhibits the thymidylate synthase to block dTMP synthesis
What molecule donates a methyl group to dUMP to synthesize dTMP?
N5, N10-Tetrahydrofolate
What drug inhibits the ribonucleotide reductase to decrease synthesis of deoxyribonucleotides?
Hydroxyurea
How is kidney stone formation associated with purine metabolism?
Deficiency of the Adenine Phosphoribosyl Transferase (APRT) in purine base salvage causes kidney stone development
What are the four enzymes involved in purine synthesis?
PRPP Synthetase, Amidophosphoribosyl transferase, Adenylosuccinate synthetase, IMP dehydrogenase
Briefly summarize purine catabolism.
GMP/AMP are broken down into guanine/adenosine by the guanosine/adenosine deaminase, respectively, to form xanthine. The xanthine oxidase then converts xanthine to uric acid for excretion in the urine.
What are the products of pyrimidine degradation?
B-alaine & B-aminoisobutyrate - Carbon skeletons can enter TCA
What vitamins play a role in 1-Carbon Metabolism?
Vitamins B6, B12, & Folate
What molecule is a common intermediate in the de novo synthesis of both purines and pyrimidines?
PRPP
How is the rate of purine synthesis controlled?
Purine synthesis is controlled by the concentration of PRPP. High PRPP increases the rate of synthesis
What enzyme in pyrimidine synthesis is allosterically regulated by CTP (inhibited) and ATP (activated)?
Aspartate Transcarbamoylase to form Carbamoyl Aspartic Acid (CAA)
What molecule is the parent of pyrimidines?
OPP
What drug inhibits the DHF reductase to limit THF availability and inhibit dTMP synthesis?
Methotrexate - treats rheumatoid arthritis, psoriasis, cancer
What is the function of Allopurinol?
Inhibits the xanthine oxidase to prevent uric acid synthesis for gout treatment
How is acute gout treated?
With anti-inflammatory agents, such as Colchicine
