Biochem- Nuleotide Metabolism I & II

Question 1

What are the two types of pathways used in Nucleotide Synthesis?

Answer 1

1. De novo synthesis — Uses metabolic precursors.
2. Salvage pathways — uses free bases and nucleosides release from nucleotide breakdowns (turnover)

Question 2

What is the major site of purine synthesis (de nova and salvage pathways)?

Answer 2

Liver.

Question 3

What does Purine De Novo synthesis begin with?

Answer 3

The synthesis of 5-phosphoribosyl 1- pyrophosphate (PRPP).

Note: Also common to pyrimidine synthesis.

Question 4

State the first 5 steps of De Novo Synthesis.

Answer 4

1. Ribose-5- phosphate — PRPP synthase — PRPP.
2. PRPP — PRPP Glutamyl Amidotransferase — 5-phosphoribosylamine
3. 5-phosphoribosylamine — phosphoribosylglycinamide synthetase — Glycinamide-ribosyl-5-phosphate. (3 atoms from glycine)
4. Glycinamide r-5-p — Formyltransferase — formyglycinamide r-5-p
5. Formyglycinamide r-5-p — vi synthetase — Formyglycinamidine r-5-p.

Question 5

Discuss steps 6-11 of De Novo Synthesis.

Answer 5

6. Formylglycinamidine r-5-p — VII Synthetase — Aminoimidazole r-5-p
7. Aminoimidazole r-5-p — VII carboxylase — Aminoimidazole carboxylate r-5-p
8. Aminoimidazole carboxylate r-5-p — IX Synthetase — Aminoimidazole succinate carboxamide r-5-p
9. Aminoimidazole succinate carboxamide r-5-p — adenylosuccinase — Aminoimidazole carboxamide r-5-p
10. Aminoimidazole carboxamide r-5-p — Formimidoimidazole carboxamide r-5-p
11. Formimidoimidazole carboxamide r-5p — IMP Cyclohydratase — Inosine monophosohate IMP

Question 6

List the two compounds IMP can be converted to.

Answer 6

Adenylate (AMP)
Guanylate (GMP)

Question 7

State the formation of AMP from IMP

Answer 7

IMP —adenylosuccinate synthase— adenylosuccinate — adenylosuccinate lyase — AMP

Question 8

State the formation of GMP from IMP

Answer 8

IMP - IMP dehydrogenase— xanthylate — XMP glutamine amidotransferase — GMP

Question 9

Nucleoside monophosphate is catalyzed to diphosphates via?

Answer 9

A base specific nucleoside monophosphate kinases.

AMP + ATP = 2ADP
GMP + ATP = GDP + ADP

Question 10

Nucleoside diphosphate is converted to nucleotides by?

Answer 10

A broad specific nucluesode diphosphate kinase.

GDP + ATP = GTP + ADP

Question 11

State the regulation of Purine De Novo Synthesis.

Answer 11

1. The synthesis of PRPP.
2. Rate limiting enzyme - PRPP synthase.

Question 12

What inhibits PRPP synthase?

Answer 12

AMP
ADP
GMP
GDP

Question 13

What is glutamine- PRPP- amidotransferase inhibit by?

Answer 13

AMP
GMP
IMP

Question 14

What does AMP and GMP feedback inhibit?

Answer 14

AMP — adenylosuccinate synthase
GMP — IMP dehydrogenase

Question 15

List the 3 bases form in purine salvage rxns.

Answer 15

Adenine
Guanine
Hypoxanthine

Question 16

List the enzymes involves in the salvage reactions of adenine, hypoxanthine and guanine.

Answer 16

Adenine — adenine phosphoribosyltransferase
Hypoxanthine — hypoxanthine -guanine phosphoribosyltransferase.
Guanine - HGPRT

Question 17

State the compounds need for the reduction of deoxynucleotides.

Answer 17

Thioredoxin
Thioredoxin reductase
NADPH

Enzyme involved: ribonucleotide reductase complex

Question 18

Describe the Purine degradation of AMP.

Answer 18

1. AMP
2. Adenosine — Inosine ( adenosine deaminase)
3. Inosine — hypoxanthine (nucleosidase)
4. Hypoxanthine — xanthine (xanthine oxidase)

Question 19

Describe the Purine degradation of GMP.

Answer 19

1.GMP — Guanosine
2. Guanosine — Guanine (nucleosidase)
3. Guanine — xanthine (guanosine deaminase)

Question 20

What is the end product for the oxidation of Xanthine?

Answer 20

Xanthine — uric acid

Note- uric acid is common in primates, birds and some animals.

Question 21

What are the disorders of Purine metabolism?

Answer 21

1. Gout
2. Lesch- Nyhan Syndrome
3. Hypouricemia - (xanthine oxidase deficiency)
4. Adenosine deaminase deficiency (T and B lymphocytes)
5. Purine nucleoside phosphorylase deficiency (T cells affected)

Question 22

Give some characteristics about Gout.

Answer 22

1. elevated concentrations of uric acid
2. Abnormal deposition of sodium urate crystals.
3. Seen more in males
4. Underexcretion of urate
5. Genetic defects in PRPP synthase.

Question 23

State the treatment for Gout.

Answer 23

1. Low diet in nucleic acids
2. Allopurinol (inhibits xanthine oxidase)

Question 24

Give some characteristics about Lesch-Nyhan Syndrome.

Answer 24

1. Hyperuricema
2. Deficiency of HGPRT
3. Excessive uric acid

Question 25

What inhibits ribonucleotide reductase?

Answer 25

Adenosine deaminase deficiency (ADA)
Purine nucleoside phosphorylase deficiency (PNPD)

Question 26

What is the function of ribonucleotide reductase complex?

Answer 26

Reduces ribose (D-ribose) sugars to 2’-deoxy derivative.

Ex. Ribonucleoside diphosphate — 2’-deoxyribonucleoside diphosphate

Question 27

Give characteristics of Purine Nucleoside phosphorylase deficiency

Answer 27

— immune system impairment
— inhibits ribonucleotide reductase.
— affects on T- cells