Ammonia and the Urea Cycle Specialized N-products

Question 1

What is the deficient enzyme in Hyperammonemia Type I?

Answer 1

CPS-I (Carbamoyl Phosphate Synthetase-I)

Question 2

What is the deficient enzyme in Hyperammonemia Type-II?

Answer 2

OTC (Ornithine transcarbamoylase)

Question 3

What is the deficient enzyme in Citrullinemia?

Answer 3

Argininosuccinate Synthetase Deficiency

Question 4

What is the deficiency enzyme in Argininosuccinic Aciduria?

Answer 4

ASL (Argininosuccinate Lyase)

Question 5

What is the deficiency in Argininemia?

Answer 5

Arginase

Question 6

A patient who presents with hyperammonemia and neurological manifestations, but no orotic acid excretion in urine, most likely has…

Answer 6

Hyperammonemia type-I

Question 7

A patient who presents with hyperammonemia, and increased orotic acid excretion in the urine most likely has…

Answer 7

Hyperammonemia type-II

Question 8

A patient who presents with hyperammonemia and increased citrulline levels is deficient in what enzyme?

Answer 8

Argininosuccinate synthetase

Citrullinemia

Question 9

Which diseases can cause black urine?

Answer 9

Alkoptonuria (Homogentistic Acid Oxidase)
Hyperammonemia Type-II (OTC)
UMP-synthetase

Question 10

Which enzyme deficiencies can cause Orotic Aciduria?

Answer 10

OTC (secondary cause)
UMP-synthetase (primary cause)
(Note: NOT homogentistic acid oxidase… which just causes black urine, but not orotic acid)

Question 11

How does one distinguish between Orotic Aciduria caused by OTC deficiency or UMP-Synthetase deficiency?

Answer 11

OTC deficiency would also be associated with hyperammonemia.

Question 12

A patient which comes to you with hyperammonemia and increased argininosuccinate levels most likely has what disease?

Answer 12

Argininosuccinic aciduria

Question 13

Argininemia is characterized by what?

Answer 13

Increased arginine levels in blood

Question 14

Which 2 amino acids transport ammonia from peripheral tissues?

Answer 14

Glutamine

Alanine

Question 15

Why can’t ammonia be directly excreted in the urine?

Answer 15

In solution, ammonia is assoc with many water molecules, therefore excretion of all metabolic ammonia would cause large water loss

Question 16

What is the role of Glutamine synthetase?

Answer 16

Synthesizes glutamine from glutamate for ammonia transport (ammonia incorp into Glutamine)

Question 17

How is free ammonia formed in the liver?

Answer 17

-Oxidative deamination of Glutamate by:
Glutamate dehydrogenase

-Glutaminase reaction of Glutamine

Question 18

What forms ammonia in the colon?

Answer 18

Bacterial Ureases

Question 19

In patients with liver cirrhosis, what happens to the ammonia formed in the colon?

Answer 19

Shunted to systemic circulation (instead of portal) and results in ammonia toxicity. (known as acquired hyperammonemia)

Question 20

Where in the body is the ONLY place the Urea cycle occurs?

Answer 20

Liver

Question 21

The first N atom of urea is donated by _______ and the second N atom is donated by_______.

Answer 21

Ammonia

Aspartate

Question 22

What is NAG? What is it used for in the Urea Cycle?

Answer 22

N-acetylglutamate;

Allosteric activator of CPS-I

Question 23

Which amino acid is thought to stimulate formation of NAG? (Thus sometimes an intervention for Hyperammonemia Type-I)

Answer 23

Arginine

Question 24

Benzoic acid is given to patients with hyperammonemia because…

Answer 24

• It combines with glycine to form Hippuric acid

- Hippurate removed one N per molecule and is excreted in the urine

Question 25

What is the only x-linked Urea Cycle Disorder?

Answer 25

OTC deficiency

Question 26

Why does OTC deficiency cause Orotic aciduria?

Answer 26

Elevated carbomoyl phosphate drives pyrimidine biosynthesis

Question 27

What is the only UCD which CANNOT be possibly treated with Arginine?

Answer 27

Arginase deficiency

Question 28

In relation to urea, kidney failure leads to elevated

Answer 28

BUN (Blood Urea Nitrogen)

Question 29

What are the effects of elevated blood ammonia?

Answer 29

• 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

Question 30

Which neurotransmitters are affected by hyperammonemia?

Answer 30

GABA

Glutamate