UREA Flashcards
NPN
What constitutes approximately 80% of all excreted nitrogen in humans?
Urea constitutes approximately 80% of all excreted nitrogen in humans. It is a waste product resulting from the breakdown of proteins and amino acids.
How does catabolism of proteins and nucleic acids contribute to the formation of urea and ammonia
During catabolism (the breakdown) of proteins and nucleic acids, amino acids are metabolized. As a result:
~ Amino acids are deaminated, leading to the production of ammonia (NH₃).
~ The liver then converts ammonia into urea through a process called the urea cycle (or Krebs-Henseleit cycle).
~ Urea is less toxic than ammonia and is excreted by the kidneys.
Where does the formation of urea primarily occur in the body?
The formation of urea primarily occurs in the liver. The liver synthesizes urea during the urea cycle, combining ammonia with carbon dioxide to form urea. Urea is subsequently transported to the kidneys for excretion in urine.
What are the products of the urea cycle?
The products of the urea cycle include one molecule of urea, one molecule of ammonia, one molecule of ATP, and one molecule of fumaric acid.
Explain the urea cycle
- Arginine from the diet or from protein breakdown is cleaved by the cytosolic enzyme arginase to urea and ornithine
- Orthinine is transported to the mitochondrial matrix via the action of ornithine translocase
- In the mitochondria ornithine transcabamoylase (OTC) catalyzes the condensation of ornithine with carbamoyl phosphate, producing citrulline
- Carbamoyl phosphate is synthesized from bicarbonate via the action of carbamoyl phosphate synthetase I (CPS-I). (HCO3−) and ammonium (NH4+) ions
- Ornithine transport into the mitochondria takes place concurrently with the export of citrulline by to the cytosol
- Citrulline is condensed with aspartate, yielding argininosuccinate, catalyzed by cytosolic argininosuccinate synthetase
- Arginine and fumarate are produced from argininosuccinate by the cytosolic enzyme argininosuccinate lyase
- Arginase cleaves urea from arginine, regenerating cytosolic ornithine, round of urea synthesis
- Fumarate, generated is reconverted to aspartate for use in the argininosuccinate synthetase reaction
What is the role of arginase in arginine metabolism, and what are its products
Arginase, a cytosolic enzyme, cleaves arginine (obtained from the diet or protein breakdown) into urea and ornithine. Urea is excreted, while ornithine continues within the urea cycle
How does ornithine reach the mitochondrial matrix during the urea cycle?
Ornithine is transported from the cytosol to the mitochondrial matrix via the action of the ornithine translocase protein.
Which enzyme catalyzes the condensation of ornithine with carbamoyl phosphate, and what product does it generate?
Ornithine transcarbamoylase (OTC), located in the mitochondria, catalyzes the condensation of ornithine and carbamoyl phosphate, resulting in the production of citrulline.
How is carbamoyl phosphate synthesized, and what are its precursors?
Carbamoyl phosphate is synthesized from bicarbonate (HCO3−) and ammonium (NH4+) ions. The enzyme responsible for this synthesis is carbamoyl phosphate synthetase I (CPS-I).
Describe the transport of ornithine within the cell during the urea cycle
Ornithine is transported into the mitochondrial matrix concurrently with the export of citrulline to the cytosol. This transport is essential for the urea cycle
What reaction occurs during the condensation of citrulline, and which enzyme catalyzes it?
Citrulline is condensed with aspartate, resulting in the formation of argininosuccinate. This reaction is catalyzed by the cytosolic argininosuccinate synthetase enzyme
What are the products of argininosuccinate when it is cleaved by the enzyme argininosuccinate lyase?
The products of argininosuccinate cleavage by argininosuccinate lyase are arginine and fumarate.
Which enzyme is responsible for cleaving urea from arginine, and what does this process regenerate?
The enzyme arginase cleaves urea from arginine. This process regenerates cytosolic ornithine for another round of urea synthesis
What happens to the fumarate generated during this process?
The generated fumarate is reconverted to aspartate for further use in the urea cycle.
Where does the cleavage of argininosuccinate occur (cytosol or mitochondria)?
The cleavage of argininosuccinate by argininosuccinate lyase occurs in the cytosol.
What is the role of ornithine in the urea cycle?
Ornithine is essential for transporting citrulline into the mitochondrial matrix during the urea cycle
What enzyme is deficient in patients with Type I hyperammonemia?
N-acetylglutamate synthetase.
6 clinical significances of urea
- As an indicator for kidney function,
- To assess hydration status,
- To determine nitrogen balance,
- To aid the diagnosis of renal disease and to verify adequacy of dialysis
- To verify adequacy of dialysis
Congestive heart failure
How does a high protein diet impact serum creatinine levels?
A high protein diet can increase serum creatinine levels due to increased protein breakdown, leading to higher creatinine production
Explain the role of increased protein catabolism in serum creatinine concentration.
Increased protein breakdown (catabolism) results in higher creatinine production, contributing to elevated serum creatinine levels.
What happens to serum creatinine when blood proteins are reabsorbed after gastrointestinal hemorrhage?
Reabsorption of blood proteins can temporarily decrease serum creatinine levels due to reduced excretion by the kidneys.
How does dehydration and decreased perfusion affect serum creatinine?
Dehydration and reduced blood flow (perfusion) to the kidneys lead to impaired creatinine excretion, resulting in elevated serum creatinine levels.
In what specific conditions would both serum creatinine and urea concentrations be increased?
Both serum creatinine and urea concentrations increase in obstructive post-renal conditions. These conditions occur when there is an obstruction in the urinary tract, preventing proper urine flow from the kidneys.
What is the significance of elevated serum creatinine levels in obstructive post-renal conditions?
Elevated serum creatinine levels indicate impaired kidney function due to the obstruction. Creatinine is a waste product that the kidneys usually filter out. When the urinary flow is obstructed, creatinine accumulates in the blood.
