Chapter 22: Metabolism of Purine Nucleotides

Question 1

Principal/major purine bases

Answer 1

• Adenine

- Guanine

Question 2

De novo synthesis of purine nucleotides

Answer 2

• Starting from scratch in the cytosol of the hepatocyte

Question 3

De novo synthesis involves

Answer 3

• 10 steps
• Energy dependent pathway via IMP
• Primarily in liver

Question 4

Two types of salvage reactions

Answer 4

• Phosphoribosylation

- Phosphorylation of purine nucleoides

Question 5

Phosphoribosylation

Answer 5

• Adding a ribose-phosphate to an existing base (therefore, salvaging it)

Question 6

Phosphorylation of purine nucleosides

Answer 6

• Adding a phosphate

- Requires less energy

Question 7

Origins of the atoms of the purine ring

Answer 7

• Aspartate amine
• Formate
• Glutamine amide
• Formate
• Glycine
• HCO3-

Question 8

De novo synthesis of purines is highly regulated and requires

Answer 8

• ATP

Question 9

Starting material for de novo synthesis of purines

Answer 9

• Ribose-5-phosphate from PPP

Question 10

Ribose-5-phosphate is converted to

Answer 10

• PRPP

Question 11

Committed step of de novo synthesis

Answer 11

• PRPP glutamyl amidotransferase

Question 12

GAR synthetase produces

Answer 12

• GAR

Question 13

Cytoplasmic enzymes needed for IMP synthesis come from

Answer 13

• Ribose-5-phosphate

Question 14

IMP is a common precursor of

Answer 14

• AMP

- GMP

Question 15

IMP is

Answer 15

• The first purine nucleotide made

- Contains hypoxanthine

Question 16

After IMP, the pathway branches to

Answer 16

• AMP and GMP

Question 17

PRPP glutamyl amidotransferase is the committed step controlled by

Answer 17

• Negative feedback

Question 18

Nucleoside monophosphates must be converted to

Answer 18

• Triphosphates by base-specific kinases

Question 19

AMP + ATP is catalyzed by/converted to

Answer 19

• Adenylate kinase

- 2 ADP

Question 20

GMP + ATP is catalyzed by/converted to

Answer 20

• Guanylate kinase

- GDP + ADP

Question 21

GDP + ATP is catalyzed by/converted to

Answer 21

• Nucleoside diphosphate kinase

- GTP + ADP

Question 22

Ribonucleotide reductase catalyzes the reduction of

Answer 22

• 2’ carbon of purine and pyrimidine diphosphates to deoxyribonucleotides (dNDPs) for DNA synthesis

Question 23

Ribonucleotide reductase is inhibited by

Answer 23

• Methotrexate (anti-cancer)

Question 24

Concentration of PRPP stimulates

Answer 24

• Purine nucleotide synthesis

Question 25

PRPP concentration is depended on

Answer 25

• Levels of ribose-5-phosphate

- Activity of PRPP synthetase

Question 26

PRPP synthetase is inhibited by

Answer 26

• ADP

- GDP

Question 27

Regulation of purine nucleotide biosynthesis involves

Answer 27

• Concentration of PRPP

- AMP and GMP

Question 28

Glutamyl amidotransferase exhibits

Answer 28

• Allosteric control

Question 29

Allosteric control of PRPP glutamyl amidotransferase is the

Answer 29

• Rate-limiting and committed step

Question 30

Allosteric control of PRPP glutamyl amidotransferase is regulated via

Answer 30

• Negative feedback from products (AMP, GMP, and IMP)

Question 31

Allosteric control of PRPP glutamyl amidotransferase is uniquely committed to

Answer 31

• Purine synthesis

- Inhibited by products at physiological concs

Question 32

Purine nucleotide degradation forms

Answer 32

• Uric acid

Question 33

Salvage reactions that minimize uric acid formation

Answer 33

• APRTase

- HGPRTase

Question 34

APRTase reaction

Answer 34

• Adenine + PRPP –> AMP + PPi

Question 35

HGPRTase reaction

Answer 35

• Hypoxanthine + PRPP –> IMP + PPi

- Guanine + PRPP –> GMP + PPi

Question 36

Purine nucleotides are synthesized de novo via

Answer 36

• Inosine monophosphate (IMP) in a 10-step pathway that requires significant metabolic investement

Question 37

The key control points of purine nucleotide biosynthesis are catalyzed by

Answer 37

• PRPP glutamyl amidotransferase
• Adenylsuccinate synthetase
• IMP dehydrogenase

Question 38

Purines are degraded to uric acid in humans, the final step being cayaltzed by

Answer 38

• Xanthine oxidase enzyme

Question 39

Salvage reactions proceed preferentially over

Answer 39

• De novo synthesis