Purine and Pyrimidine Metabolism

Question 1

Enzyme that activates Ribose-5-Phosphate coming from HMP shunt

Answer 1

Phosphoribosyl pyrophosphate (PRPP) Synthetase

Question 2

Primary end product of pyrimidine synthesis

Answer 2

UMP

Question 3

Enzyme that reduces Nucleotide Diphosphates (NDPs) to their Deoxy form (dNDPs) which is the one needed for DNA synthesis

Answer 3

Ribonucleotide reductase

Question 4

Chemo drug inhibiting Ribonucleotide reductase

Answer 4

Hydroxyurea (S phase); RNR also inhibited by dADP and dATP

Question 5

Enzyme that converts d-Uracil-MP to d-Thymine-MP by methylation

Answer 5

Thymidylate synthase. REQUIRES Tetrahydrofolate (THF)

Question 6

Chemo drug inhibiting Thymidylate synthase

Answer 6

5-Fluorouracil (S phase)

Question 7

Enzyme that converts DHF to THF

Answer 7

Dihydrofolate reductase (DHFR)

Question 8

Drugs inhibiting DHFR

Answer 8

Methotrexate (eukaryotic cells, such as in Chemo), Trimethoprim (prokaryotic, such as in UTI bacteria), Pyrimethamine (protozoal)

Question 9

Rate limiting enzyme in De Novo Purine Synthesis

Answer 9

PRPP Aminotransferase (converts PRPP to 5-Phosphoribosylamine)

Question 10

Inhibitors of the rate limiting enzyme in De Novo Purine Synthesis

Answer 10

Inhibitors of PRPP Aminotransferase: Allopurinol (used for gout) and 6-Mercaptopurine (antineoplastic) nucleotides

Question 11

Amino acids used for De Novo Purine Synthesis

Answer 11

“GAG”: Glycine and the two acidic amino acids, Aspartate and Glutamine

Question 12

THF’s role in De Novo Purine Synthesis

Answer 12

Carbon donor to produce Inosine MP (contains the purine base, Hypoxanthine) from 5-phosphoribosylamine

Question 13

Enzyme primarily responsible for the Purine Salvage Pathway

Answer 13

HGPRT (Hypoxanthine-Guanine Phosphoribosyltransferase); 90% of Hypoxantine and Guanine is recycled back while 10% is excreted as Xanthine and to Uric Acid

Question 14

Spastic cerebral palsy, Self-mutilation (hands, lips), Hyperuricemia, Early death, XLR, Orange crystals in diapers of infants

Answer 14

Lesch-Nyhan syndrome (near-complete deficiency of HGPRT); crystals are sodium urate crystals, since absence of HGPRT shunts hypoxantine-guanine to Excretion Pathway

Question 15

Enzyme deficiency in Severe Combined Immunodeficiency (SCID), a disease where patients lack both B- and T-cell function

Answer 15

Adenosine deminase (ADA), responsible for converting Adenosine to Inosine (in the Salvage Pathway); Consequent accumulation of dATP in RBCs inhibit RNR, ultimately inhibiting the production of other deoxynucleotide precursors for DNA synthesis

Question 16

Aside from inhibition of PRPP Aminotransferase (rate-limiting) in De Novo Purine Synthesis, Allopurinol inhibits this enzyme in the Excretion Pathway of Hypoxantine and Guanine

Answer 16

Xanthine Oxidase

Question 17

Crystals accumulating in acute gouty arthritis (negatively birefringent and needle shaped)

Answer 17

Monosodium urate crystals - initiates neutrophil-mediated acute inflammation first affecting the big toe (Podagra)

Question 18

Uricosuric drug used for Chronic Hyperuricemia (caused by underexcretion)

Answer 18

Probenecid

Question 19

Drugs used to reduce inflammation in acute attacks of gout

Answer 19

Colchicine, Indomethacin

Question 20

Hyperuricemia due to excessive alcohol consumption is due to

Answer 20

Alcohol competes with uric acid in renal excretion

Question 21

Hyperuricemia in cancer patients undergoing chemotherapy

Answer 21

Tumor Lysis Syndrome

Question 22

(+) orotic aciduria, (+) hyperammonemia, (-) megaloblastic anemia. Enzyme deficiency?

Answer 22

Ornithine transcarbamylase in Urea cycle

Question 23

(+) orotic aciduria, (-) hyperammonemia, (+) megaloblastic anemia. Enzyme deficiency?

Answer 23

UMP Synthase in Pyrimidine synthesis

Question 24

(-) orotic aciduria, (-) hyperammonemia, (+) megaloblastic anemia. Enzyme deficiency?

Answer 24

Folate deficiency, not necessarily (+) enzyme deficiency