Metabolism of purine nucleotides

Question 1

PRPP

Answer 1

5-phosphoribosyl-1-pyrophosphate
important precursor in synthesis of nucleotides
made from ribose 5 phosphate
R5P +ATP -> AMP + PRPP
enzyme: ribose phosphate pyrophosphokinase
PRPP provides phosphoribose unit to purine and pyrimidine

Question 2

1. PRPP -> PRA/ 5-phosphoribosyl amine

Answer 2

Gln -> Glu

enzyme: GLN PRPP AMIDOTRANSFERANSE

Question 3

2. PRA -> GAR/ 5- phosphoribosyl glycinamide

Answer 3

+glycine
ATP -> ADP +Pi
enzyme: GAR SYNTHETASE

Question 4

3. GAR -> FGAR / 5-pr formyl- glycinamide

Answer 4

N10-fomyl-THF -> THF

enzyme: GAR TRANSFORMYLASE

Question 5

4. FGAR -> FGAM/ 5-pr-formyl-glycinamidine

Answer 5

Gln -> Glu
ATP -> ADP +Pi
enzyme: FGAM SYNTHETASE

Question 6

5. FGAM -> AIR / 5-pr-5-amino-imidazole

Answer 6

ATP -> ADP +Pi

enzyme: AIR SYNTHETASE

Question 7

6. AIR ->CAIR/ 5-pr-4 carboxy 5 amino imidazole

Answer 7

+CO2

enzyme: AIR CARBOXYLASE

Question 8

7. CAIR -> SACAIR / 5 pr succinyl 5 aminoimidazole 4 carboxamide

Answer 8

+Asp
ATP -> ADP+Pi
enzyme: SACAIR SYNTHETASE

Question 9

8.SACAIR -> ACAIR / 5 pr 5 aminoimidazole 4 carboxamide

Answer 9

• fumarate

enzyme: ADENILOSUCCINASE (ASA)

Question 10

9. ACAIR -> FACAIR/ 5 prs formamidoimidazole 4 carboxamide

Answer 10

N10 formyl THF -> THF

enzyme: ACAIR TRANSFORMYLASE

Question 11

10. FACAIR -> IMP

Answer 11

• H20

enzyme: IMP CYCLOHYDROLASE

Question 12

IMP -> AMP

Answer 12

IMP - ADENYLOSUCCINATE SYNTHASE - adenylosuccinate - ASA - AMP

Question 13

IMP -> GMP

Answer 13

IMP - IMP DH - XMP - GMP SYNTHASE - GMP

Question 14

Myoadenylate deaminase deficiency

Answer 14

cramps, NH3, urate levels not elevated

Question 15

Lesh-Nyen syndrome

Answer 15

HPRT deficiency
GTP levels of basal ganglions low 
-mental retardation
-self mutilation
-aggression
-hyperuricemia

Question 16

Regulation of salvage reactions

Answer 16

+ PRPP
- IMP,GMP, AMP
Gln PRPP amidotransferase

Question 17

Salvage pathways

Answer 17

Hypoxanthine + PRPP -> IMP + PPi : HGPRT
Guanine + PRPP -> GMP + PPi: HGPRT
Adenine + PRPP -> AMP + PPi : APRT

Question 18

Catabolism of AMP

Answer 18

AMP - 5 NUCLEOTIDASE - adenosine - ADENOSINE DEAMINASE - inosine - PURINE NUCLEOSIDE PHOSPHORYLASE - hypoxanthine

Question 19

Catabolism of GMP

Answer 19

GMP - 5 NUCLEOTIDASE - guanosine - PURINE NUCLEOSIDE PHOSPHORYLASE - guanine

Question 20

ADA, PNP, ADA+PNP enzyme deficiency

Answer 20

immunodeficiency (non-HIV AIDS)
T-cell deficiency
high adenosine -> high dATP =
- inhibition of ribonucleotide reductase
- inhibition of DNA synthesis
- inhibition of cell division
PEG-ADA enzyme therapy, Gene therapy

Question 21

Production of urate

Answer 21

Hypoxantine - xantine - urate : XANTINE OXIDASE
H2O +O2 -> H2O2
Guanine - xantine - urate: GUANASE, XANTINE OXIDASE
H2O -> NH3

Question 22

Hyperuricemia (gout)

Answer 22

urate crystals
Na-urate crystals -> stones
urate in soft tissues and joints causes inflammation, pain because rate has low solubility
medication: allopurinol (comp inhibitor of hypoxantine)

Question 23

Origins of Hyperuricemia

Answer 23

1. PRPP overproduction
   - mutation in allosteric site
   - overprod of R5P
   - e.g. von Gierke disease
2. Absence of purine salvage reactions
   - e.g. HPRT deficiency
3. Low ATP level, disturbed ATP metabolism
   - heavy exercise, fructose intolerance
4. Secondary reasons
   - tissue damage, cancer