Nucleotide Metabolism

Question 1

What is the committed step in purine synthesis

Answer 1

Conversion of PRPP into phosphoribosylamine

Question 2

If your body is consuming lots of ATP and has high levels of inorganic phosphate, how will that effect purine synthesis

Answer 2

It will increase the synthesis of purines to compensate for that additional need of ATP

Question 3

How is folate used in purine synthesis

Answer 3

Part of it is used in the construction of IMP

IMP is the branch point in purine synthesis

Question 4

How is balance of the concentration between the two pool of primary purines maintained

Answer 4

ATP and GTP are used for the construction of GMP and AMP, respectively

Question 5

What is the rate limiting step in pyrimidine synthesis, and how is it regulated

Answer 5

Formation of carbamoyl phosphate by carbamoyl phosphate synthetase II
Allosterically activated by PRPP and inhibited by UTP/UMP
Aspartate transcarbamoylase forms carbamoyl aspartate- it is allosterically inhibited by CTP

Question 6

UMP is made from what two molecules

Answer 6

PRPP and orotate

Question 7

What is Orotic aciduria

Answer 7

Inability to convert orotic acid to UMP, causes megaloblastic anemia

Question 8

What happens after UMP is formed

Answer 8

It is converted to UDP which is then either converted to dUDP or UTP
dUDP is converted to dUMP which is bridge to dTTP (thymidine) production

Question 9

What is the branch point molecule in pyrimidine and purine synthesis

Answer 9

UDP in pyrimidine

IMP in purine

Question 10

Which one, purine or pyrimidine synthesis, uses PRPP as a platform to construct the base on

Answer 10

Purine synthesis

Pyrimidines generate the base independently of PRPP

Question 11

Methotrexate

Answer 11

Antineoplastic agent used to treat cancer

Prevents oxidation of NADPH by DHFR, disrupts DNA replication in rapidly dividing cells

Question 12

Sulfa drugs

Answer 12

Competitively inhibit the bacterial enzyme that incorporates PABA into folate. Disrupts DNA replication in bacteria

Question 13

How do drugs that deprive cells of GMP work (what do they target)

Answer 13

They target IMP dehydrogenase to prevent IMP from being formed, which is required for formation of GMP

Question 14

What is the significance of the oxidation level of purines

Answer 14

Catabolic processes include steps where oxygen is added to molecules to make them more polar (more oxygen, further in the catabolic process)

Question 15

ADA

Answer 15

Adenosine deaminase, plays important role in purine metabolism by catalyzing the irreversible step in the pathway

Question 16

SCID

Answer 16

Invariably fatal genetic disorder where both B and T cells are crippled. Most common form is X-linked, second most common form is due to deficiency of purine catabolic enzyme ADA. This leads to a buildup of dADP and eventually blocks formation of all other dNDPs. Impairs DNA synthesis

Question 17

Gout

Answer 17

Caused by either overproduction or, more commonly, underexcretion of uric acid. This causes deposits of sodium urate in the joints of the extremities or the kidneys. Treated with allopurinol which inhibits xanthine oxidase

Question 18

General overview of pyrimidine catabolism

Answer 18

Converted to readily metabolized ketogenic or glucogenic, water soluble compounds

Question 19

Uracil/cytosine are catabolized to what

Answer 19

Malonyl CoA

Question 20

Thymine is catabolized to what

Answer 20

Succinyl CoA

Question 21

Lesch-Nyhan syndrome

Answer 21

Results from defects in HGPRT in purine salvage pathway, leads to primary hyperuricemia and can cause gout, kidney stones, mental retardation

Question 22

Acyclovir method of action

Answer 22

Thymidine kinase generates dTMP from dT. Acyclovir undergoes phosphorylation by viral thymidine kinase at a rate that exceeds that of cellular thymidine kinase. Acyclovir is eventually converted to GTP which is incorporated into viral cells, but lacks a 3’ hydroxyl group and terminates DNA replication