Zusammenfassung der Ressource
Purine Synthesis
- De Novo Synthesis
- liver
- most active
- requires
- aa
- aspartate,
glycine,
glutamine
- CO2
- NH3
- ribose-5-phosphate
- ring assembled
- PRPP
- activated
form of
ribose
- 1 ATP
- 5-phosphoribosyl-1-amine
- amdio-phosphoribosyltransferase
- committed step
- need glutamine
- hypoxanthine
- attached to ribose-P
- inosinate (IMP)
- precursor
- AMP
- use 1 GTP
- GMP
- use 1 ATP
- 3 ATP
- THF derivatives
- N10-formyl-THF
- Salvage Pathway
- recycle free purine bases
- adenine + PRPP --> adenylate PPi
- APRT
- hypoxanthine --> IMP + PPi
- HGPRT
- guanine + PRPP --> GMP + PPi
- HGPRT
- conserve ATP
- recycle
nucleoside
bases
- nucleotide
monophosphates
- limits De-Novo
- catalyzed by
- APRT
- HGPRT
- deficiency
- severe
- Lesch-Nyhan syndrome
- partial
- gout
- brain
- Purine Metabolism
- regulation
- PRPP synthetase
- (-) ADP, GDP
- PRPP aminotransferase
- (-) A & G nucleotides
- mono, di, tri
- (-) IMP
- (+) PPRP
- IMP dehydrogenase
- (-) GMP
- ATP substrate
- excess ATP = increase GMP
- Adenylosuccinate synthetase
- (-) AMP
- GTP substrate
- excess GTP = increase AMP
- Disorders
- phosphoribosylpyrophosphate
synthetase superactivity
- X-linked
- recessive
- purine overproduction
- excess purine degraded
- hyperuricemmia
- gout
- neurologic
developmental
abnormalities
- diagnosis
- enzyme studies
- RBCs, skin fibroblasts
- treatment
- allopurinol
- low-purine diet
- adenylosuccinase deficiency
- autosomal
- recessive
- effects
- mental retardation
- autistic behavior
- seizures
- diagnosis
- ID elevations in
CSF/urine
- succinylaminoimidazole
carboxaminde riboside
- succinyladenosine
- treatment
- none effective
- adenosine deaminase deficiency
- function
- convert
adenosine/deoxyadenosine to
inosine/deoxyinosinee
- more breakdown
- excretion
- accumulation of adenosine
- converted to dATP
- inhibits
ribonucleotide
reductase
- DNA
replication
compromised
- no other dNTPs
synthesized
- immune cells susceptible
- SCID
- destroy B/T lymphocytes
- need to
proliferate
dramatically
- affected by inability of
DNA synthesis
- xanthine oxidase deficiency
- function
- catalyze uric
acid production
- from
xanthine/hypoxanthine
- build up of xanthine
- precipitate in urine
- stones, hematuria,
urinary colic, UTI
- diagnosis
- low plasma
uric acid
- high plasma
hypoxanthine/xanthine
- liver/intestinal
biopsy rare
- treatment
- high fluid intakte
- minimize stone formation
- allopurinol
- Lesch-Nyhan Syndrome
- function loss HGPRT
- X-linked
- symptoms
- severe gout
- high [uric acid/sodium urate]
- defect in reg
- nucleotide metabolism
- treatment
- colchicine
- inflammation
- allopurinol
- inhibit xanthine oxidase
- diet
- low purine
- pain
- crystals
- inflammation
- malfunction of
nervous system
- no treatment
- death before 20 yo
- adenine pohsphoribosyltransferase
deficiency
- autosomal
- recessive
- inability to salvage adenine
- purine synthesis
- accumulated adenine
- oxidized
- 2,8-dihydroxyadenine
- precipitates
- renal colic,
infections, renal
failure
- diagnosis
- elevated levels (urine)
- 2,8-dihydroxyadenine
- 8-hydroxadenine
- adenine
- normal
- serum uric acid
- Catabolism
- source
- breakdown
- RNA
- DNA
- nucleases
- phosphomonoesterase
- product
- uric acid
- xanthine oxidase
- abundant in
liver/intestine
- salvage pathway
- Purine Nucleotide Cycle
- increase muscle activity
- increase TCA cycle
- generate NADH
- more ATP
- muscle lacks
anaplerotic
enzymes
- replenish TCA cycle
- fumarate
- purine nucleotide cycle
- Synthesis Inhibitors
- inhibit proliferation
- leukocytes
- azathioprine
- immunosuppresant
- organ transplant
- autoimmune
- rheumatoid arthritis
- inflammatory bowel
disease
- Crohn's
- ulceerative colitis
- Purine Analogs
- acycloguanines
- treats
- HSV-1 HSV-2
- shingles
- chicken
pox