Purine Metabolism

Question 1

difference between a nucleoside and a nucleotide

Answer 1

• nucleoside is a nitrogenous base and a ribose rugar

- mucleotide is a nitrogenous base and ribose sugar with a triphosphate attached to the sugar

Question 2

nucleotides can make

Answer 2

• high energy intermediates

- DNA and RNA

Question 3

what is IMP

Answer 3

• inosine monophosphate

- one phosphate, a nitrogenous base and a ribose sugar

Question 4

GMP and AMP are formed from

Answer 4

• IMP
• requires ATP and GTP as an energy source (ATP for GMP formation and GTP for AMP formation)
• this helps to ensure equal levels of purines

Question 5

conversion of monophosphates to diphosphates and triphosphates

Answer 5

• mono to di is catalyzed by a kinase that is base specific but not sugar specific
• the conversion of di to tri is not base specific, nor sugar specific

Question 6

activation of antiviral nucleoside analogues

Answer 6

• require the formation of their corresponding 5’ triphosphate
• for example AZT must be converted to AZT triphosphate by thymine kinase and then nucleotide diphosphate kinase in order to be an active drug

Question 7

how many reactions are required to form a purine and what does each reaction need

Answer 7

-4, ATP driven reactions

Question 8

what is the committed step of purine biosynthesis?

Answer 8

• when the glycosidic bond is formed during the first atom of the purine ring is incoporated
• this is catalyzed by PRPP amidotransferase

Question 9

what is the first purine synthesized

Answer 9

• inosonic acid (IMP)

- this is the precursor to AMP and GMP

Question 10

where are the enzymes for purine biosynthesis located

Answer 10

in the cytosol

Question 11

what organs are de novo synthesis particularly active in?

Answer 11

liver and the placenta

Question 12

which enzymes facilitate purine salvage

Answer 12

• HGPRT: guanine to GMP and hypoxanthine to IMP

- APRT: adenine to AMP

Question 13

gout

Answer 13

• characterized by elevated uric aacid levels in the blood
• due to a variety of metabolic abnormalities
• urate crystals are deposited in the cartilage of joints resulting in pain and disability
• also deposits in the kidney

Question 14

enzyme defects that lead to gout

Answer 14

• partial defect in HGPRT: this causes reduced IMP and GMP formation via the salvage pathway. PRPP accumulates and causes activation of the de novo purine biosynthesis. Also, lower IMP and GMP levels result in reduced feedback inhibition of the de novo path
• a PRPP synthetase def: less susceptible to feedback inhibition by purine nucleotides
• glucose 6 P def: this leads to increased utilization of the PPS and consequently to excessive production of ribose 5 P, the intermediate of PRPP

Question 15

allopurinol

Answer 15

• an analogue of hypoxanthine, it is effective in lowering uric acid levels in the blood. it is a competitive inhibitor of xanthine oxidase
• upon treatment, hypoxanthine and xanthine accumulate, they are more soluble than uric acid and are more easily excreted

Question 16

lesch nyhan syndrome

Answer 16

• infants with this disease lack a functional HGPRT
• symptoms include self mutilation, mental illness and gout like symptoms owing to elevated uric acid in serum
• marked increase in the rate of purine biosynthesis via the de novo pathway
• the mechanism by which the def causes central nervouse system disorders remains unknown
• however, in normal subjects, HGPRT activity is highest in the brain, suggestin the importance of the purine salvage pathway in this tissue

Question 17

sulfonamides

Answer 17

• first antibacterial agent employed by humans
• bacteria must synth folic acid compounds, mammals depend on preformed folate
• sulfonamides resemble p aminobenzoic acid and inhibit synthesis of folate in bacteria, blocking the formation of an essential compound

Question 18

6 mercaptopurine

Answer 18

• inhibitor of purine synthesis
• used in the treatment of acute leukemia
• functions as an analogue of hypoxanthine
• prevents the production of AMP and GMP