dNTP Synthesis

Question 1

When in the cell cycle does the amount of dNTP increase

Answer 1

S Phase

Question 2

One of the major differences between ribonucleotides and deoxyribonucleotides

Answer 2

conversion of ribose to 2’-deoxy ribose

Question 3

Enzyme for conversion of ribose to 2’-deoxy ribose

Answer 3

ribonucleotide reductase

Question 4

How hydroxyurea functions

Answer 4

Quenches the ocygen radical in the R2 subunit to OH, which targets bone marrow wbc production (reduces inflamation)

Question 5

Regulation of R1 subunit of ribonucleotide reductase

Answer 5

ATP stimulates, dATP inhibits

Question 6

The conversion of U to T is carried out by

Answer 6

thymidylate synthase

Question 7

Substrates for thymidylate synthase

Answer 7

N5,N10-methylenetetrahydrofolate (from folic acid) and dUMP

Question 8

How 5-fluorouracil works

Answer 8

When reacting, dUMP, thymidylate synthase, and methylenetetrahydrofolate are all covalently bound together. To be regenerated, dUMP must have a proton abstracted. 5-fluorouracil does not allow this to occur because F is so electronegative

Question 9

Products of thymidylate synthase

Answer 9

dTMP and dihydrofolate

Question 10

How does dihydrofolate get back to THF (and how does methotrexate fit)

Answer 10

Dihydrofolate reductase, which used NADPH as a reducing agent. Methotrexate binds to dihydrofolate reductase at a higher affinity

Question 11

Purine catabolism

Answer 11

Final propduct is uric acid

Question 12

How SCID (deficiency of adenosine deaminase) works

Answer 12

Deficiency of adenosine deaminase leads to a build up of dAMP, which is converted to dATP by T and B lymphocytes. High levels of dATP feedback inhibits ribonucleotide reductase choking off the productions of dCTP, dGTP, and dTTP. Leads to problem in cell proliferation and immune response involving T and B lymphocytes.

Question 13

Cause of gout

Answer 13

Approximately 20% of gout cases result from metabolic disorders that increase uric acid synthesis.

Relatively low solubility of sodium ureate (~ 7.3/7.4 mg/dL) in serum and its relatively high concentrations within the human body (males, ~ 7 mg/dL) leads to condensation of crystals in joints

Question 14

Lesh-Nyhan syndrome

Answer 14

A deficiency of the purine salvage enzyme hypoxanthine guanine phosphoribosyl transferase, leads to increase in pRpp, which overrides purine synthesis control. Gout like symptoms

Question 15

Why is cobalamin deficiency bad

Answer 15

Cobalamin helps convert MeFH4 to FH4, and eventually purine synthesis