Biochemistry Lec-11: Ammonia Metabolism

Questions and Answers

What is the primary function of the urea cycle in the liver?

To synthesize amino acids from other molecules.

To break down fatty acids for energy production.

To convert glucose into glycogen for storage.

To detoxify ammonia and produce urea for excretion. (correct)

Which of the following conditions can lead to acquired hyperammonemia?

Deficiency of the enzyme glutamine synthetase.

Increased production of red blood cells.

Liver cell failure due to cirrhosis or hepatitis. (correct)

Increased dietary protein intake.

What is the main symptom associated with inherited hyperammonemia?

Persistent coughing.

Increased urination.

Mental retardation. (correct)

Severe muscle weakness.

How does ammonia intoxication affect the citric acid cycle?

It inhibits the activity of enzymes in the cycle. Signup and view all the answers

Which of the following is NOT a direct consequence of hyperammonemia in the brain?

Increased levels of ATP. Signup and view all the answers

What is the normal range for plasma urea concentration in milligrams per deciliter (mg/dl)?

15-45 mg/dl. Signup and view all the answers

Which of the following is NOT an amino acid involved in the urea cycle?

Glycine. Signup and view all the answers

What is the primary site of urea formation in the body?

Liver. Signup and view all the answers

Which of the following is NOT a product of the catabolism of α-ketoacids?

Glycerol Signup and view all the answers

What is the role of N-acetyl glutamate in the urea cycle?

It acts as an allosteric activator of carbamoyl phosphate synthase I. Signup and view all the answers

Where does the formation of citrulline take place in the urea cycle?

Mitochondria Signup and view all the answers

What is the fate of ornithine in the urea cycle?

It is regenerated and reused in the cycle. Signup and view all the answers

Which of the following molecules is NOT directly involved in the formation of carbamoyl phosphate?

Fumarate Signup and view all the answers

What is the primary function of the urea cycle?

To remove ammonia from the body. Signup and view all the answers

Which of the following statements accurately describes the role of α-ketoglutarate in the fate of α-ketoacids?

It is a product of the catabolism of amino acids. Signup and view all the answers

How many ATP molecules are used in the formation of carbamoyl phosphate?

2 Signup and view all the answers

What is the primary toxic effect of ammonia on the body?

Damage to the central nervous system Signup and view all the answers

Which amino acid is primarily involved in transporting ammonia from peripheral tissues to the liver?

Glutamine Signup and view all the answers

What enzyme is responsible for the formation of ammonia from glutamine in the kidneys?

Glutaminase Signup and view all the answers

Ammonia can be produced in the intestine by the action of bacterial enzymes on which of the following?

Dietary amino acids Signup and view all the answers

Which function of glutamine helps in the detoxification of ammonia in the brain?

Formation of glutamine from ammonia and glutamate Signup and view all the answers

What is the fate of ammonia after it is produced in the body?

Converted into non-essential amino acids and urea Signup and view all the answers

What is the normal concentration range of ammonia in blood?

10 - 80 ug/dL Signup and view all the answers

Which of the following is NOT a source of ammonia in the body?

Breakdown of fatty acids Signup and view all the answers

Study Notes

Ammonia (NH3)

Ammonia is a toxic substance, especially to the central nervous system, and must be converted into urea in the liver.
Ammonia is transported from peripheral tissues to the liver via:
- Glutamine (most tissues)
- Alanine (muscle)
Blood contains traces of ammonia (10-80 ug/dL).
Sources of ammonia include:
- Transdeamination of amino acids (mainly in liver)
- Glutamine metabolism (kidneys)
- Purines and pyrimidines metabolism
- Intestinal bacteria action on dietary amino acids and urea

Fate of Ammonia

Formation of non-essential amino acids through transdeamination
Formation of glutamine:
- Glutamine synthetase is a mitochondrial enzyme present in many tissues (kidney, brain)
- Glutamine functions:
  - Regulation of acid-base balance
  - Removes toxic effect of ammonia in brain
  - Source of N3 and N9 of purines bases
  - Used in detoxication of phenyl acetic acid
Formation of urea
Excretion in urine

Ammonia Intoxication

Definition: Excess ammonia toxic to the central nervous system
Symptoms:
- Flapping tremors, slurring speech, blurring vision, and vomiting in infancy
- High concentration of ammonia can cause coma and death
Types and causes of hyperammonemia:
- Acquired hyperammonemia:
  - Liver cell failure
  - Renal failure
  - Shunt operation between portal and systemic circulation
  - Collaterals between portal and systemic circulation (cirrhosis, hepatitis)
- Inherited hyperammonemia:
  - Genetic deficiency of one of five enzymes of urea cycle
Mechanism of ammonia intoxication:
- Ammonia reacts with α-Ketoglutarate by glutamate dehydrogenase enzyme
- Depletes α-Ketoglutarate, leading to decrease in ATP and energy production
- Symptoms of ammonia intoxication and coma

Urea

Urea is the main end product of protein metabolism
Urea formation is the pathway through which the liver converts toxic ammonia into non-toxic urea
Site of urea formation:
- Liver is the only site for urea formation
- Urea is transported in blood to the kidney to be excreted in urine
Plasma urea:
- Normal level: 15-45 mg/dL
- Diagnostic importance: measures kidney function, high levels indicate kidney disease (uremia)

Urea Formation (Krebs' Henseleit Cycle)

The first two reactions occur in mitochondria, others in cytosol
Six amino acids involved: ornithine, citrulline, arginosuccinate, Aspartate, Arginine, and N-acetyl glutamate
Steps:
- Formation of Carbamoyl phosphate:
  - Occurs in mitochondria
  - Needs CO2, ammonia, phosphate, and ATP
  - Catalyzed by Carbamoyl phosphate synthase I
- Formation of citrulline:
  - Occurs in mitochondria
  - Carbamoyl phosphate reacts with ornithine
- Formation of arginosuccinate:
  - Citrulline reacts with Aspartate in cytosol
- Cleavage of arginosuccinate:
  - Into Arginine and Fumarate
- Cleavage of Arginine into ornithine and urea:
  - Ornithine passes back to mitochondria
  - Urea passes to blood to be excreted by kidney in urine

Fate of α-Keto-Acids

The α-ketoacid remaining after transamination and deamination of amino acids may undergo:
- Reamination by ammonia to form the corresponding amino acid
- Catabolized to form seven products:
  - Pyruvate
  - Acetyl CoA
  - Acetoacetyl CoA
  - Fumarate
  - Oxaloacetate
  - α-Ketoglutarate
  - Succinyl CoA
These products enter different pathways leading to:
- Synthesis of glycogen or glucose
- Synthesis of lipids
- Complete oxidation into CO2 and H2O

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Description

This quiz covers the metabolism of ammonia, its toxicity, and its conversion to urea in the liver. It's part of a biochemistry course taught by Dr. Wael Sobhy Darwish.