Metabolism of purine nucleotides Flashcards
PRPP
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
- PRPP -> PRA/ 5-phosphoribosyl amine
Gln -> Glu
enzyme: GLN PRPP AMIDOTRANSFERANSE
- PRA -> GAR/ 5- phosphoribosyl glycinamide
+glycine
ATP -> ADP +Pi
enzyme: GAR SYNTHETASE
- GAR -> FGAR / 5-pr formyl- glycinamide
N10-fomyl-THF -> THF
enzyme: GAR TRANSFORMYLASE
- FGAR -> FGAM/ 5-pr-formyl-glycinamidine
Gln -> Glu
ATP -> ADP +Pi
enzyme: FGAM SYNTHETASE
- FGAM -> AIR / 5-pr-5-amino-imidazole
ATP -> ADP +Pi
enzyme: AIR SYNTHETASE
- AIR ->CAIR/ 5-pr-4 carboxy 5 amino imidazole
+CO2
enzyme: AIR CARBOXYLASE
- CAIR -> SACAIR / 5 pr succinyl 5 aminoimidazole 4 carboxamide
+Asp
ATP -> ADP+Pi
enzyme: SACAIR SYNTHETASE
8.SACAIR -> ACAIR / 5 pr 5 aminoimidazole 4 carboxamide
- fumarate
enzyme: ADENILOSUCCINASE (ASA)
- ACAIR -> FACAIR/ 5 prs formamidoimidazole 4 carboxamide
N10 formyl THF -> THF
enzyme: ACAIR TRANSFORMYLASE
- FACAIR -> IMP
- H20
enzyme: IMP CYCLOHYDROLASE
IMP -> AMP
IMP - ADENYLOSUCCINATE SYNTHASE - adenylosuccinate - ASA - AMP
IMP -> GMP
IMP - IMP DH - XMP - GMP SYNTHASE - GMP
Myoadenylate deaminase deficiency
cramps, NH3, urate levels not elevated
Lesh-Nyen syndrome
HPRT deficiency GTP levels of basal ganglions low -mental retardation -self mutilation -aggression -hyperuricemia
Regulation of salvage reactions
+ PRPP
- IMP,GMP, AMP
Gln PRPP amidotransferase
Salvage pathways
Hypoxanthine + PRPP -> IMP + PPi : HGPRT
Guanine + PRPP -> GMP + PPi: HGPRT
Adenine + PRPP -> AMP + PPi : APRT
Catabolism of AMP
AMP - 5 NUCLEOTIDASE - adenosine - ADENOSINE DEAMINASE - inosine - PURINE NUCLEOSIDE PHOSPHORYLASE - hypoxanthine
Catabolism of GMP
GMP - 5 NUCLEOTIDASE - guanosine - PURINE NUCLEOSIDE PHOSPHORYLASE - guanine
ADA, PNP, ADA+PNP enzyme deficiency
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
Production of urate
Hypoxantine - xantine - urate : XANTINE OXIDASE
H2O +O2 -> H2O2
Guanine - xantine - urate: GUANASE, XANTINE OXIDASE
H2O -> NH3
Hyperuricemia (gout)
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)
Origins of Hyperuricemia
- PRPP overproduction
- mutation in allosteric site
- overprod of R5P
- e.g. von Gierke disease - Absence of purine salvage reactions
- e.g. HPRT deficiency - Low ATP level, disturbed ATP metabolism
- heavy exercise, fructose intolerance - Secondary reasons
- tissue damage, cancer
