Disease of Nucleotide Metabolism Flashcards
Lesh-Nyhan Syndrome
Buildup of uric acid leading to swollen joints and neuro probs like facial grimacing and involuntary writhing
Also get uric acid crystals in kidney and UT
Why uric acid crystals in L-N dz?
Because lower pH in these areas and as pH decreases, more acidic and more crystalization
Also more concentrated here
What can help reduce formation of uric acid stones?
Hydration
L-N behavior
Self-mutilation, facial grimacing, involuntary writhing
L-N inheritance
X-linked recessive
L-N pathology
Defect in hypoxanthine phosphoribosyl transferase (HPRT)…this normally recycles hypoxanthine and guanine back…without it, xanthine oxidase works overtime to take hypoxanthine to xanthine and xanthine to uric acid
L-N blood levels
Increased xanthine, guanine, hypoxanthine, and uric acid
L-N treatments
Extra-corporeal shock wave lithotripsy
Allopurinol inhibits xanthine oxidase so less uric acid made (leads to buildup of hypoxanthine)
Allopurinol mech
Converted to oxypurinol by xanthine oxidase…won’t leave active site…suicide substrate
Gout spiral
Crystal form…WBCs attack…crystals pop cells..cells release proteins…proteins call in more WBCs…proteins lower pH making it possible for more crystals to form
Gout risk factors
Men (40-50) Women after menopause Overweight Meds Kidney dz or BP (bc decreased clearnace) Relatives with gout
Alcohol and gout
Beer and hard liquor make it worse
Wine might help?
Where can you get purines?
Diet or purine synthesis
How can you get rid of pruines?
Renal and gut
3 classes of hyperuricemia tx drugs
Uricostatics - inhibt production of uric acid (inhibit xanthine oxidase…allopurinol)
Uricolytics - promote breakdown of uric acid (activate uricase in liver to turn into allantoin)
Uricosurics - promote excretion of uric acid by kidney
Why are uricolytics helpful
Breakdown insoluble uric acid into soluble allantoin
Gout sufferers should avoid
Yeast, nutes, sardines, meats,
ADA def mech
Increased levels of dATP because uric acid pathway is shut off
dATP effect
Inhibits ribonucleotide reductase which is needs to make the 4 dNTPs…lack of dNTPs means decreased ability to divide…results in weakened immune system because B and T cells cannot proliferate
ADA is one type of
SCID…need germ free environment
Txsa for ADA def
PEG-ADA - adagen is ERT…can be given immediately to help control
Gene therapy - modification of stem cells…can cure…must be stabilized
BMT - replace with stem cells..cure…must be stabilized, better in young patients
Gene therapy and ADA
Use retrovirus and insert into T cells…then transplant the T cells
