UREA CYCLE DEFECTS

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OBJECTIVES
Describe the pathway for nitrogen disposal
Define the consequences of defects in these
reactions
Current treatment
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UREA CYCLE DEFECTS

• OMIM
• Urlhttp//www.ncbi.nih.gov/Omim/

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From Burton 1998 Pediatr. 102 1-9
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Components of the urea cycle
N-acetyl glutamatee Synthetase (NAGS)
Carbamyl-Phosphate synthetase
Ornithine transcarbamylase
Argininosuccinate synthetase
Argininosuccinate lyase
Arginase
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glutamate AcetylCoA
NH3
NAGS
HCO3-
ATP
CPS I
N-acetylglutamate
Carbamyl-PO4
ornithine
Carbamyl-PO4
OTC
ornithine
Citrulline
UREA
Rase
Orotic acid
Arginine
Citrulline
Fumarate
AL
AS
pyrimidines
Argininosuccinate
Aspartate
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NH3
glutamate AcetylCoA
NAGS
HCO3-
ATP
CPS I
N-acetylglutamate
Carbamyl-PO4
ornithine
Carbamyl-PO4
OTC
ornithine
Citrulline
UREA
Rase
Orotic acid
Arginine
Citrulline
Fumarate
AL
AS
pyrimidines
Argininosuccinate
Aspartate
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NH3
glutamate AcetylCoA
NAGS
HCO3-
ATP
CPS I
N-acetylglutamate
Carbamyl-PO4
ornithine
Carbamyl-PO4
OTC
ornithine
Citrulline
UREA
Rase
Orotic acid
Arginine
Citrulline
Fumarate
AL
AS
pyrimidines
Argininosuccinate
Aspartate
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NH3
glutamate AcetylCoA
NAGS
HCO3-
ATP
CPS I
N-acetylglutamate
Carbamyl-PO4
ornithine
Carbamyl-PO4
OTC
ornithine
Citrulline
UREA
Rase
Orotic acid
Arginine
Citrulline
Fumarate
AL
AS
pyrimidines
Argininosuccinate
Aspartate
9
NH3
glutamate AcetylCoA
NAGS
HCO3-
ATP
CPS I
N-acetylglutamate
Carbamyl-PO4
ornithine
Carbamyl-PO4
OTC
ornithine
Citrulline
UREA
Rase
Orotic acid
Arginine
Citrulline
Fumarate
AS
AL
pyrimidines
Argininosuccinate
Aspartate
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(No Transcript)
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NH3
glutamate AcetylCoA
NAGS
HCO3-
ATP
CPS I
N-acetylglutamate
Carbamyl-PO4
ornithine
Carbamyl-PO4
OTC
ornithine
Citrulline
UREA
Rase
Orotic acid
Arginine
Citrulline
Fumarate
AL
AS
pyrimidines
Argininosuccinate
Aspartate
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NH3
glutamate AcetylCoA
NAGS
HCO3-
ATP
CPS I
N-acetylglutamate
Carbamyl-PO4
ornithine
Carbamyl-PO4
OTC
ornithine
Citrulline
UREA
Rase
Orotic acid
Arginine
Citrulline
Fumarate
AL
AS
pyrimidines
Argininosuccinate
Aspartate
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Treatment for urea cycle defects along with PMD
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glutamate AcetylCoA
NH3
NAGS
HCO3-
ATP
CPS I
N-acetylglutamate
glutamic ?-semialdehyde
Carbamyl-PO4
ornithine
Carbamyl-PO4
OTC
OAT
ornithine
Citrulline
UREA
Rase
Orotic acid
Arginine
Citrulline
Fumarate
AL
AS
pyrimidines
Argininosuccinate
Aspartate
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TAKE HOME LESSONS
Ammonia toxicity is predominating consequence
of Urea cycle defects
Inherited defects are known for each step of the
cycle
All defects inherited as AR traits except for
OTC which is X-linked
Differential diagnosis is made by accumulated
intermediate analysis, enzyme activity
measurements, and DNA analysis
Treatment includes protein restriction, and use
of compounds to conjugate ammonia