L32- Purine Metabolism

Question 1

The nitrogen atoms in purines come from which amino acids?

Answer 1

Glycine, glutamine and aspartate.

Question 2

In which organ does the de novo synthesis of purines primarily occur?

Answer 2

Liver.

Question 3

PRPP, or 5-phosphoribosyl-1-pyrophosphate, is an important intermediate in the biosynthesis of both purines and pyrimidines. What is its immediate precursor?

Answer 3

Ribose-5-phosphate.

Question 4

Which enzymes are involved in the conversion of ribose-5-phosphate to 5-phosphoribosylamine?

Answer 4

PRPP synthetase and glutamine PRPP amidotransferase.

Question 5

Which enzyme catalyzes the formation of 5-phosphoribosyl-1-pyrophosphate (PRPP) from ribose-5-phosphate and ATP?

Answer 5

PRPP synthetase.

Question 6

What is the committed step in the de novo biosynthesis of purines?

Answer 6

The conversion of PRPP to 5-phosphoribosylamine by glutamine PRPP amidotranferase.

Question 7

The amine group on 5-phosphoribosylamine comes from which amino acid?

Answer 7

Glutamine.

Question 8

How many molecules of ATP are required for the formation of inosinate (IMP) from 5-phosphoribosylamine?

Answer 8

4 ATP molecules are required.

Question 9

Which form of tetrahydrofolate (THF) is required for the formation of inosinate (IMP) from 5-phosphoribosylamine?

Answer 9

N10-formyl-tetrahydrofolate.

Question 10

What is the first purine to be synthesized in the de novo biosynthesis of purines?

Answer 10

Inosinate (IMP).

Question 11

The synthesis of AMP from IMP requires ____ as an energy source and _____ as an amino group donor.

Answer 11

GTP; aspartate.

Question 12

The synthesis of GMP from IMP requires ____ as an energy source and _____ as an amino group donor.

Answer 12

ATP; glutamine.

Question 13

True or False. The conversion of monophosphate nucleosides to diphosphate nucleosides is catalyzed by kinases that are sugar-specific but not base-specific.

Answer 13

False. The conversion of monophosphates to disphosphates is catalyzed by kinases that are base-specific but not sugar-specific.

Question 14

Which broad-specificity enzyme catalyzes the interconversion of diphosphate nucleosides with triphosphate nucleosides?

Answer 14

Nucleoside diphosphate kinase.

Question 15

The carbon atoms in purines come from which compounds?

Answer 15

Carbon dioxide, N10-formyl THF and glycine.

Question 16

Which amino acid contributes both nitrogen and carbon atoms in the de novo biosynthesis of purines?

Answer 16

Glycine.

Question 17

In which cellular compartment does the synthesis of purines occur?

Answer 17

Cytosol.

Question 18

In which tissue(s) does the salvage pathway for purine biosynthesis primarily occur?

Answer 18

Mostly in extrahepatic tissues.

Question 19

What are the substrates and products of the reaction(s) catalyzed by hypoxanthine-guanine phosphoribosyl transferase (HGPRT)?

Answer 19

HGPRT is involved in the salvage pathway of purine biosynthesis. It catalyzes the formation of GMP from a guanine base and PRPP, and the formation of IMP from a hypoxanthine base and PRPP.

Question 20

Which enzyme in the salvage pathway of purine biosynthesis catalyzes the formation of AMP from an adenine base and PRPP?

Answer 20

Adenine phosphoribosyl transferase (APRT).

Question 21

What is the predominant direction and products of the reaction catalyzed by purine nucleoside phosphorylase?

Answer 21

The predominant direction is degradative (as opposed to base salvaging) and produces a free base and ribose-1-phosphate.

Question 22

What class of enzymes is able to hydrolyze nucleotides from the diet or tissue breakdown to form nucleosides?

Answer 22

Phosphatases.

Question 23

True or False. The enzyme adenosine deaminase can deaminate adenosine, 2’-deoxyadenosine and other 6-aminopurines.

Answer 23

True.

Question 24

What is the product formed by the deamination of adenosine by adenosine deaminase?

Answer 24

Inosine.

Question 25

What products are formed from the breakdown of inosine by purine nucleoside phosphorylase?

Answer 25

Hypoxanthine and ribose-1-phosphate.

Question 26

What is the function of xanthine oxidase in purine catabolism?

Answer 26

It oxidizes hypoxanthine to uric acid in two steps.

Question 27

The enzyme xanthine oxidase converts hypoxanthine to uric acid in two steps. What is the product of the first step?

Answer 27

Xanthine.

Question 28

What is the common intermediate in the production of uric acid from hypoxanthine and guanine?

Answer 28

Xanthine.

Question 29

The enzyme guanine deaminase catalyzes the deamination of guanine. What is the product of this reaction?

Answer 29

Xanthine.

Question 30

Regulation of the de novo synthesis of purines occurs at which steps?

Answer 30

At the PRPP synthetase reaction, the PRPP amidotransferase reaction, and at the formation of AMP and GMP from IMP.

Question 31

Name the inhibitor(s) of PRPP synthetase.

Answer 31

PRPP synthetase is subject to feedback inhibition by AMP, ADP, ATP, GMP, GDP, and GTP.

Question 32

Name the allosteric inhibitor(s) of PRPP amidotransferase.

Answer 32

AMP and GMP.

Question 33

What condition can result from the overproduction of purines or the decreased excretion of uric acid?

Answer 33

Gout.

Question 34

Allopurinol is a competitive inhibitor of which enzyme?

Answer 34

Xanthine oxidase.

Question 35

Which hypoxanthine analogue is effective in lowering the levels of uric acid in the blood, and can therefore be used to treat gout?

Answer 35

Allopurinol.

Question 36

Which purine derivative acts as a hypoxanthine analogue and is commonly used to treat acute leukemias?

Answer 36

6-mercaptopurine.

Question 37

How does a partial defect in HGPRT lead to gout?

Answer 37

It causes reduced IMP and GMP formation via the salvage pathway. As a result, there is reduced feedback inhibition of the de novo pathway, leading to accumulation of PRPP.

Question 38

Which enzyme may lose its sensitivity to feedback inhibition by purine nucleotides, resulting in an overproduction of PRPP that may in turn lead to gout?

Answer 38

PRPP synthetase.

Question 39

Which enzyme deficiency can lead to gout due to an overproduction of ribose-5-phosphate?

Answer 39

Glucose-6-phosphatase deficiency.

Question 40

What is the enzymatic defect that leads to Lesch-Nyhan syndrome?

Answer 40

Lack of functional HGPRTase, resulting in an increase in purine synthesis via the de novo pathway.

Question 41

What condition can result from adenosine deaminase deficiency?

Answer 41

Severe combined immunodeficiency syndrome (SCID), a condition in which patients lack both B and T lymphocyte functions.

Question 42

What class of antibiotics interferes with folate synthesis in bacteria by functioning as p-aminobenzoic acid analogues?

Answer 42

Sulfonamides.