Ammonia and the Urea Cycle Specialized N-products Flashcards
What is the deficient enzyme in Hyperammonemia Type I?
CPS-I (Carbamoyl Phosphate Synthetase-I)
What is the deficient enzyme in Hyperammonemia Type-II?
OTC (Ornithine transcarbamoylase)
What is the deficient enzyme in Citrullinemia?
Argininosuccinate Synthetase Deficiency
What is the deficiency enzyme in Argininosuccinic Aciduria?
ASL (Argininosuccinate Lyase)
What is the deficiency in Argininemia?
Arginase
A patient who presents with hyperammonemia and neurological manifestations, but no orotic acid excretion in urine, most likely has…
Hyperammonemia type-I
A patient who presents with hyperammonemia, and increased orotic acid excretion in the urine most likely has…
Hyperammonemia type-II
A patient who presents with hyperammonemia and increased citrulline levels is deficient in what enzyme?
Argininosuccinate synthetase
Citrullinemia
Which diseases can cause black urine?
Alkoptonuria (Homogentistic Acid Oxidase)
Hyperammonemia Type-II (OTC)
UMP-synthetase
Which enzyme deficiencies can cause Orotic Aciduria?
OTC (secondary cause)
UMP-synthetase (primary cause)
(Note: NOT homogentistic acid oxidase… which just causes black urine, but not orotic acid)
How does one distinguish between Orotic Aciduria caused by OTC deficiency or UMP-Synthetase deficiency?
OTC deficiency would also be associated with hyperammonemia.
A patient which comes to you with hyperammonemia and increased argininosuccinate levels most likely has what disease?
Argininosuccinic aciduria
Argininemia is characterized by what?
Increased arginine levels in blood
Which 2 amino acids transport ammonia from peripheral tissues?
Glutamine
Alanine
Why can’t ammonia be directly excreted in the urine?
In solution, ammonia is assoc with many water molecules, therefore excretion of all metabolic ammonia would cause large water loss
What is the role of Glutamine synthetase?
Synthesizes glutamine from glutamate for ammonia transport (ammonia incorp into Glutamine)
How is free ammonia formed in the liver?
-Oxidative deamination of Glutamate by:
Glutamate dehydrogenase
-Glutaminase reaction of Glutamine
What forms ammonia in the colon?
Bacterial Ureases
In patients with liver cirrhosis, what happens to the ammonia formed in the colon?
Shunted to systemic circulation (instead of portal) and results in ammonia toxicity. (known as acquired hyperammonemia)
Where in the body is the ONLY place the Urea cycle occurs?
Liver
The first N atom of urea is donated by _______ and the second N atom is donated by_______.
Ammonia
Aspartate
What is NAG? What is it used for in the Urea Cycle?
N-acetylglutamate;
Allosteric activator of CPS-I
Which amino acid is thought to stimulate formation of NAG? (Thus sometimes an intervention for Hyperammonemia Type-I)
Arginine
Benzoic acid is given to patients with hyperammonemia because…
- It combines with glycine to form Hippuric acid
- Hippurate removed one N per molecule and is excreted in the urine
What is the only x-linked Urea Cycle Disorder?
OTC deficiency
Why does OTC deficiency cause Orotic aciduria?
Elevated carbomoyl phosphate drives pyrimidine biosynthesis
What is the only UCD which CANNOT be possibly treated with Arginine?
Arginase deficiency
In relation to urea, kidney failure leads to elevated
BUN (Blood Urea Nitrogen)
What are the effects of elevated blood ammonia?
- Alpha-ketoglutarate converted to glutamate via glutamate dehydrogenase. This results in decreased TCA cycle activity which reduced ATP synthesis.
- Reduced Na/K ATPase activity which increases osmotic pressure which eventually leads to cell death
Which neurotransmitters are affected by hyperammonemia?
GABA
Glutamate
