3

Question 1

Purine bases. Source of ring atoms: (6)

Answer 1

CO2, Gln, Gly, Asp, N10, THF, PRPP

Question 2

Pyrimidine bases. Source of ring atoms: (6)

Answer 2

HCO3-, Gln, Asp, N5, N10, methylene THF

Question 3

Pyrimidine Catabolism

Answer 3

Dietary pyrimidines converted readily to metabolized ketogenic or glucogenic, water soluble compounds such as malonyl CoA, methyl malonyl CoA and succinyl CoA

Question 4

De Novo Synthesis of Purine Nucleotides

Answer 4

1. PRPP reacts w/ Glutamine and forms –> PRA (PRPP activates the C-1’ ribosyl carbon for the formation of an N-glycosidic bond-“NH2 gets added onto C-1” ** Stimulates: PRPP Inhibits: GMP, AMP, IMP 2. Glycine molecule (along w/ more things) is added to the growing purine precursor (9 steps) and makes IMP **Inhibits: Methotrexate 3. IMP is precursor for both AMP & GMP **Feedback inhibition (AMP prevents more AMP and GPM prevents more GMP) 4. AMP/GMP are phosphorylated –> ADP/GDP (they can go to the ATP/GTP level as well, if so they are used for energy or for RNA synthesis) 5. ADP/GDP are reduced to deoxyribose (dADP & dGDP) and then to dATP/dGTP(used for DNA synthesis) or just from the original ADP/GDP to ATP/GTP

Question 5

PRPP (phosphoribosyl pyrophosphate) is made from what 2 things?

Answer 5

ribose phosphate & ATP

Question 6

Committed step in purine synthesis

Answer 6

Formation of the phosphoribosyl amine (PRA)

Question 7

Purine ring is synthesized attached to _________

Answer 7

The purine ring is synthesized attached to ribose phosphate. The ribose is initially contributed by Phosphoribosylpyrophosphate (PRPP)

Question 8

Methotrexate

Answer 8

An antineoplastic agent that targets dihydrofolate reductase that converts in the liver (cancer drug) This inhibition disrupts DNA replication in rapidly dividing cells (inhibitor of DNA synthesis) It binds dihydrofolate reductase 100x more tightly Inhibits the metabolism of folic acid

Question 9

Tetrahydrofolate

Answer 9

FH4 can’t be made in the body. You get it from the folate vitamin

Question 10

Synthesis of purine nucleotides is controlled by feedback regulation

Answer 10

Question 11

The pyrimidine ring is synthesized from ______ & _______

Answer 11

The pyrimidine ring is synthesized from CARBAMOYL PHOSPHATE & ASPARTATE by aspartate transcarbamoylase

Question 12

De Novo Synthesis of Pyrimidine Nucleotides

Answer 12

3 phases:

1. Fabrication of orotate ring
2. Attach PRPP to form UMP
3. Convert UMP to uridine, cytosine, and thymidine (deoxy)nucleotides

Question 13

The pyrimidine ring is made from carbamoyl phsophate and aspartate by aspartate- transcarbamoylase

Answer 13

The first step and also the COMMITED STEP is the formation of n-carbamoyl aspartate from aspartate and carbamoyl phosphate

Question 14

When does the ring form in De Novo Synthesis of Pyrimidine Nucleotides?

Answer 14

The ring formes before the reaction with PRPP

Question 15

Orotic aciduria

Answer 15

A human hereditary disorder involving the synthesis of the pyrimidine nucleotides

Treated w/ oral uridine

Question 16

After pyrimidine biosynthesis, DNA is then synthesized from dATP, dCTP, dGTP and dTTP. The concentration of _____ is the limiting factor

Answer 16

dTTP

Question 17

Sulfa drugs

Answer 17

• Antibacterial agents that act as competitive inhibitors of the bacterial enzyme that incorporates p-aminobenzoic acid (PABA) into folate
• This inhibition disrupts DNA replication in bacteria
• Humans acquire folate as a vitamin from the diet, sulfa drugs selectively affect bacteria

Answer 18