Biochemistry: Nitrogen Metabolism and Enzymes

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Questions and Answers

What is the primary function of glutaminase?

To synthesize ammonia

To break down D amino acids

To generate glutamate and glutamine (correct)

To detoxify peroxide

Ammonia is less toxic than the ammonium ion.

False

What is the function of catalase in the body?

To detoxify peroxide

Under physiological conditions, the concentration of the ammonium ion is approximately _____ times higher than ammonia.

100 Signup and view all the answers

Match the following cycles or enzymes with their respective functions:

Glucose-Alanine Cycle = Conserves glucose backbones L Amino Acid Oxidase = Generates peroxide using FMN D Amino Acid Oxidase = Breaks down D amino acids Urea Cycle = Detoxifies ammonia Signup and view all the answers

What is the primary consequence of urea cycle defects?

Hyperammonemia Signup and view all the answers

Patients with urea cycle defects can tolerate high protein diets.

False Signup and view all the answers

What role does Alpha Keto Glutarate play in treating hyperammonemia?

It transaminates nitrogen to form glutamate. Signup and view all the answers

The urea cycle converts ammonia into __________, which is then excreted from the body.

urea Signup and view all the answers

Match the following urea cycle enzymes with their functions:

Carbamylphosphate synthetase = Converts bicarbonate and ammonium ion to carbonyl phosphate Ornithine Transcarbamylase = Catalyzes the formation of citrulline from ornithine N Acetylglutamate = Plays a regulatory role in the urea cycle Citrulline = Intermediate in the urea cycle Signup and view all the answers

Where do the first two enzymes of the urea cycle reside?

Mitochondrial matrix Signup and view all the answers

Carbonyl phosphate is an activated form of urea.

True Signup and view all the answers

What happens to nitrogen from ammonia in the urea cycle?

It is converted into urea. Signup and view all the answers

Which enzyme is the rate-limiting enzyme of the urea cycle?

Carbamylphosphate Synthetase 1 Signup and view all the answers

The urea cycle is activated by high levels of ammonia in the blood.

False Signup and view all the answers

What are the primary reactants for the production of Carbamyl phosphate?

Bicarbonate and Ammonium ion Signup and view all the answers

Argininosuccinate is converted to __________ in the urea cycle.

Arginine Signup and view all the answers

Match the following urea cycle enzymes with their corresponding products:

CPS 1 = Carbamyl phosphate OTC = Citrulline Argininosuccinate Synthetase = Argininosuccinate Arginase = Urea Signup and view all the answers

Which of the following is NOT a precursor of urea?

Glutamate Signup and view all the answers

Deficiencies in enzymes of the urea cycle can lead to hyperammonemia.

True Signup and view all the answers

Study Notes

Urine and Ammonia

Urine is acidic and traps ammonia in the form of ammonium ions, which are less toxic than ammonia.
Glutaminase and Asparaginase play a role in nitrogen metabolism.
Glutaminase removes nitrogen, generating glutamate and glutamine, which act as intracellular nitrogen carriers.
Asparaginase is typically less critical, but it is an enzyme involved in nitrogen metabolism.
L and D amino acid oxidases are involved in breaking down amino acids.

L and D Amino Acid Oxidases

L amino acid oxidase uses FMN (flavine mononucleotide) and produces peroxide as a byproduct.
D amino acid oxidase utilizes FAD and also produces peroxide.
The D amino acid oxidase is important for breaking down D amino acids, which are often found in bacterial infections.

The Glucose-Alanine Cycle (Cahill Cycle)

This cycle helps conserve glucose backbones.
It involves converting alanine to pyruvate and then pyruvate back to glucose in the liver.
Glucose is primarily used by the brain and red blood cells.
It prevents muscle cells from using glucose, as this would lead to fatty acid and ketone body production.

The Importance of Catalase

Catalase is an enzyme present in peroxisomes.
It detoxifies peroxide generated by L and D amino acid oxidases.

Ammonia Toxicity

Ammonia levels exceeding 10 micrograms per liter are toxic to cells.
Ammonium ions are less toxic, with a toxic level of around half a milligram.
However, physiological conditions maintain a 100-fold higher concentration of ammonium ions compared to ammonia.

Urea Cycle

A complete blockage in any step of the urea cycle is fatal.
The urea cycle detoxifies ammonia in the liver, converting it into urea.
Urea is then excreted from the body.

Location of Urea Cycle Enzymes

The first two enzymes, Carbamylphosphate synthetase 1 (CPS1) and Ornithine transcarbamylase, are located in the mitochondrial matrix.
The remaining three enzymes are located in the cytosol.

Carbamyl Phosphate Synthetase 1 (CPS 1)

CPS 1 is the initial enzyme in the urea cycle.
It catalyzes the reaction between bicarbonate and ammonium ions, forming carbamyl phosphate.
Carbamyl phosphate is an activated form of urea, containing a phosphate group on one end and a nitrogen group on the other.

Ornithine Transcarbamylase

This enzyme catalyzes the reaction between ornithine and carbamyl phosphate, leading to the formation of citrulline.

Urea Cycle Reactions:

CPS1: Bicarbonate + Ammonium ion → Carbamyl phosphate
Ornithine Transcarbamylase: Ornithine + Carbamyl phosphate → Citrulline
Arginosuccinate Synthetase: Citrulline + Aspartate → Arginosuccinate
Arginosuccinate Lyase: Arginosuccinate → Arginine
Arginase: Arginine → Urea

Hyperammonemia

Hyperammonemia refers to elevated ammonia levels in the blood.
Deficiencies in urea cycle enzymes can cause hyperammonemia.

Activation of the Urea Cycle

The urea cycle is activated by a flow of nitrogen.
N-Acetylglutamate Synthetase regulates this, producing N-acetylglutamate, which activates CPS1.

Urea Precursors

Aspartate, free ammonium ions, and carbamyl phosphate are the precursors providing nitrogen for the urea cycle.

Hyperammonemia: Urea Cycle

The urea cycle involves two key enzymes: CPS 1 and OTC.
CPS 1 is the rate-limiting enzyme, regulated by N-acetylglutamate.

Hyperammonemia: Process

1. Ammonium ion + Bicarbonate → Carbamyl phosphate (via CPS 1)
1. Carbamyl phosphate → Citrulline (via OTC)
1. Citrulline → Argininosuccinate (via Arginosuccinate Synthetase)
1. Arginosuccinate → Arginine (via Arginosuccinate Lyase)
1. Arginine → Urea (via Arginase)
1. Urea → Ornithine (via Arginase)

Hyperammonemia: Diagnosis

High ammonia levels are a key indicator.
Decreased BUN (blood urea nitrogen) levels.
Blood glutamine levels are elevated.

Enzyme Deficiencies

Ornithine Transcarbamylase (OTC) Deficiency

Hyperammonemia, elevated carbamylphosphate levels, and elevated orotic acid levels (due to stimulated pyrimidine biosynthesis) are characteristic.
Diagnosis is established through Orotic Acid Urea testing.

Carbamylphosphate Synthetase 1 (CPS 1) Deficiency

Characterized by hyperammonemia, reduced carbamylphosphate levels, and reduced orotic acid levels.
Diagnosis is confirmed by the absence of Orotic Acid Urea.

Clinical Signs and Symptoms

Central edema
Lethargy
Convulsions
Coma
Death
Note: Ammonia can pass the blood-brain barrier, leading to central edema.

Hyperammonemia Summary

Enzyme Deficiency: | Symptoms: | Diagnosis:
OTC Deficiency: | Hyperammonemia, Elevated Carbamylphosphate, Elevated Orotic Acid | Orotic Acid Urea
CPS1 Deficiency: | Hyperammonemia, Decreased Carbamylphosphate, Decreased Orotic Acid | No Orotic Acid Urea

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Description

This quiz covers key concepts of nitrogen metabolism, including the roles of urine, ammonia, and critical enzymes like glutaminase and asparaginase. Additionally, it delves into L and D amino acid oxidases and the Glucose-Alanine Cycle, highlighting their biological significance and interconnections. Test your understanding of these biochemical processes!