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65904
Purine Synthesis
Descripción
Biochemistry Mapa Mental sobre Purine Synthesis, creado por hardinbc el 01/05/2013.
Sin etiquetas
biochemistry
biochemistry
Mapa Mental por
hardinbc
, actualizado hace más de 1 año
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Creado por
hardinbc
hace más de 11 años
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Resumen del Recurso
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
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