Urea Cycle Disorders Flashcards
Urea cycle purpose
Get nitrogen out of the body
Final product of urea cycle
Make arginine that becomes urea
Arginine supplementation does what?
Replaces low arginine levels
Stimulates NAGS reaction which stimulates CPS 1 (enzyme important for capturing ammonia)
Stimulates metabolites that flow into ornithine and cirtulline which keep the cycle going
Urea is major disposal form of
Amino groups from proteins
Urea is sole source of
Endogenous production of arginine
Urea formation and excretion locations
Formation in liver…excretion in kidney
Urea cycle disorder causes
Could be from cofactor…could be from enzyme defect
Dysfunction of urea cycle results in
Neurologic changes because no other ways to clear ammonia
Hyperammonemia type 1 defect
CPS 1 defect
Hyperammonemia type 2 defect
Ornithine transcarbamoylase
Citrullinemia defect
Argininosuccinate synthetase
Argininosuccinic aciduria defect
Argininosuccinase
Hyperarginemia defect
Arginase
2 most severe types
CPS-1 and OTCase
Main clinical manifestations of urea dzs
Most are neurologic
Neurologic posturing
Clenached position not normal
Eyes and urea cycle
Papilledema due to intercranial pressure
Liver and urea cycle defect
Hepatomegaly
Tx for urea cycle disorders
Decrease protein Dialysis Arginine chloride and nitrogen scavengers (IV) Arginine become essential Liver transplant
Benzoate
Converte to benzl CoA and then to hippurate…scavenges glycine
Phenylacetate
Converted to phenylacetyl-CoA and then phenylacetylglutamine…scavenges glutamine (glutamine has 2 nitrogens)
Glycine and glutamine good targets because
They are used fuel urea cycle…just need to get below toxic level
Hyperammonemia type 1
CPS 1 defect
Rapid hyperammonemia during newborn period
Risk of hyperammonemia througout life
Hyperammonemia type 2
OTC deficinecy
X-linked
Often deadly
Could be asymptomatic til adulthood and females that are heterozygous could have variety of symptoms
Ctrullinemia type 1
Arginosuccinate synthase def
Autosomal rec
Lethargy with mental retardation
Hyperammonemia
tx for citrullinemia
Restrict protein and emphasize other caloric sources
Use nitrogen scavengers
May need dialysis
Long term administer sodium phenylbutyrate and arginine
May need liver transplant
Argininosuccinic aciduria
ASL deficiency
Rapid onset hyperammonemia
Past point in cycle where waste nitrogen incorportated into cycle
Only tx is arginine supplmentation
Trichorrhexias nodosa (response to arginine)
Hepatic enlargement and increased transaminases
Hyperargininemia
ARG def
Not typically rapid onset hyperammonemia
Spasticity with tremor, ataxia and choreoathetosis
Growth affected
