Biochemistry of Urea Cycle Disorders

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Questions and Answers

Where is carbamoyl phosphate synthetase I located?

In the mitochondria of liver cells. (correct)

In the cytoplasm of pancreatic cells.

In the nucleus of liver cells.

In the mitochondria of kidney cells.

What activates carbamoyl phosphate synthetase I?

N-acetyl glutamate and bicarbonate.

N-acetyl glutamate and Mg++ ions. (correct)

Glutamate and Mg++ ions.

Bicarbonate and S-adenosyl methionine.

Which condition leads to increased urea in blood?

Low protein diet.

High protein diet. (correct)

Excessive hydration.

Healthy liver function.

What is the main consequence of a diseased liver on urea levels?

Decreased urea in blood and urine. Signup and view all the answers

What metabolic disorder is characterized by a deficiency of carbamoyl phosphate synthetase?

Hyperammonaemia type I. Signup and view all the answers

What is the main mechanism by which the brain removes ammonia?

Formation of glutamine from glutamate Signup and view all the answers

In the kidneys, what is the primary source of ammonia production?

Deamination of glutamine Signup and view all the answers

What percentage of excreted ammonia in urine comes from deamination of glutamine?

60% Signup and view all the answers

Which enzyme catalyzes the deamination of glutamine in the kidneys?

Glutaminase Signup and view all the answers

What is the primary end product of amino acid catabolism?

Urea Signup and view all the answers

What is the normal blood level of urea in mg/dl?

10-50 mg/dl Signup and view all the answers

What role does ammonia play in the urea cycle?

It forms carbamoyl phosphate Signup and view all the answers

What is the main nitrogenous compound excreted in urine?

Urea Signup and view all the answers

What is the primary role of HCl in protein digestion?

To activate pepsinogen into pepsin Signup and view all the answers

Which enzyme is specifically responsible for converting casein into insoluble calcium caseinate in infants?

Rennin Signup and view all the answers

Which of the following statements about pepsin is true?

It hydrolyzes bonds of specific amino acids Signup and view all the answers

In which part of the digestive system does protein digestion begin?

In the stomach Signup and view all the answers

What triggers the activation of trypsinogen into trypsin?

Enterokinase Signup and view all the answers

What is the end product of pepsin digestion?

Polypeptides and peptones Signup and view all the answers

Why is rennin absent in the adult stomach?

The pH is unsuitable for its activity Signup and view all the answers

What is the significance of the milk clot formation in infants?

It provides a sense of fullness Signup and view all the answers

What is the primary action of trypsin?

Hydrolyzes the bonds between basic amino acids like arginine and lysine Signup and view all the answers

Where is carboxypeptidase secreted from?

Pancreatic acini Signup and view all the answers

How is pro-carboxypeptidase activated?

By trypsin Signup and view all the answers

Which of the following best describes elastase?

An endo-peptidase acting specifically on elastin Signup and view all the answers

What is the end product of carboxypeptidase action on polypeptides?

Single amino acids Signup and view all the answers

Which enzymes are responsible for acting on tri-peptides and di-peptides?

Tri-peptidases and di-peptidases Signup and view all the answers

What is the primary site of absorption for dietary proteins in the intestines?

Jejunum and ileum Signup and view all the answers

What type of transport is primarily responsible for the absorption of L-amino acids in the intestine?

Active transport requiring energy Signup and view all the answers

How many molecules of ATP are required for the absorption of one amino acid?

3 Signup and view all the answers

What is the primary route for nitrogen excretion from the body?

Urine Signup and view all the answers

What is the daily protein requirement for an adult male?

30-60 gm/day Signup and view all the answers

Which state of nitrogen balance occurs when nitrogen intake exceeds nitrogen output?

Positive nitrogen balance Signup and view all the answers

What is the main source of nitrogen to the body?

Proteins and nucleoproteins Signup and view all the answers

What happens to glutathione when it reacts with an amino acid?

It forms ɤ-Glutamyle amino acid Signup and view all the answers

In which of the following conditions would one expect a positive nitrogen balance?

Lactation Signup and view all the answers

What is the quantitative difference between nitrogen intake and output called?

Nitrogen balance Signup and view all the answers

What is the primary mechanism of amino acid absorption in the small intestine?

Active transport via carrier proteins Signup and view all the answers

Which vitamin plays a role in the absorption of amino acids?

Pyridoxal (Vitamin B6) Signup and view all the answers

What occurs when an amino acid is fed in excess compared to others in its group?

Retarded absorption of other amino acids in the same group Signup and view all the answers

Which amino acid transport system involves the co-transport of sodium?

Carrier proteins transport system Signup and view all the answers

What role does ATP play in amino acid absorption?

Provides energy for active transport systems Signup and view all the answers

Under what condition does the absorption of proteins without digestion normally occur?

Normally in infants through colostrum Signup and view all the answers

What is a possible consequence of unprocessed protein absorption in adults?

Eliciting an antigen-antibody reaction Signup and view all the answers

What does the glutathione transport system do in terms of amino acid movement?

Transports amino acids from lumen to intestinal cells requiring energy Signup and view all the answers

Study Notes

Protein Metabolism - Digestion

Protein digestion is necessary for absorption, resynthesis of necessary proteins, and immune processes.
Mouth: No protein digestion occurs.
Stomach:
- Hydrochloric acid (HCl) converts native protein to acid-metaprotein, leading to denaturation of secondary, tertiary, and quaternary protein structures.
- Pepsin, an enzyme secreted by chief cells in the gastric mucosa (pH 1-2), is secreted as pepsinogen (inactive form).
- Pepsinogen is activated by HCl or pepsin to form pepsin.
- Pepsin is an endopeptidase that hydrolyzes peptide bonds between phenylalanine, tyrosine, and tryptophan.
- End products: a mixture of protein, proteoses, peptones, and polypeptides.
Duodenum:
- Trypsin and chymotrypsin (secreted as trypsinogen and chymotrypsinogen by pancreatic acini, pH 8).
- Trypsinogen and chymotrypsinogen are activated by enterokinase to become trypsin and chymotrypsin.
- Trypsin is an endopeptidase that hydrolyzes peptide bonds between basic amino acids (arginine and lysine).
- Chymotrypsin is also an endopeptidase but acts on peptide bonds between uncharged aromatic amino acids.
- End products: proteoses, peptones, and polypeptides.
- Carboxypeptidase (source: pancreatic acini, pH 8) is an exopeptidase, and activates by trypsin). Cleaves the C-terminal amino acids in peptides. End product: single amino acids.
- Elastase(s) (source: pancreatic acini, pH 8), also activated by trypsin. An endopeptidase that acts on non-polar amino acids (Val, Leu, Ser & Ala) to produce peptides.
Small Intestine:
- Aminopeptidase (source: glands of Bruner and Lieberkuhn, pH 5-7). An exopeptidase acting on the peptide bond at the free NH2 of polypeptides. End product: free amino acids.
- Dipeptidases and tripeptidases (source: glands of Bruner and Lieberkuhn, pH 5-7). Exopeptidases acting on dipeptides and tripeptides respectively. End product: free amino acids.

Protein Metabolism - Absorption

Dietary proteins are almost completely digested into amino acids.
Absorption site: jejunum and ileum.
Absorption is an active process requiring energy (ATP hydrolysis).
Mechanism of absorption:
- Endocytosis (a small amount of intact protein is absorbed and degraded in lysosomes).
- Active transport: L-amino acids (naturally occurring) are absorbed actively using specific carrier proteins present in small intestines, similar to glucose absorption. Carrier proteins have sites for amino acids and sodium.
- Competition during absorption: amino acids of the same group compete with each other. Vitamin B6 and manganese play a role in amino acid absorption.
- Simple diffusion (D-amino acids are absorbed by simple diffusion).
Absorption of proteins without digestion occurs in infants (absorption of immunoglobulins from colostrum). In adults, some intact proteins may be absorbed (antigen-antibody reaction).

Protein Metabolism - Amino Acid Absorption Mechanisms

Two mechanisms:
- Carrier proteins transport system: main system for amino acid absorption. An active process requiring ATP to transport amino acids and sodium, one carrier protein for each group of amino acids
- Glutathione transport system (r-Glutamyl cycle): glutathione transports amino acids from the intestinal lumen into the cytosol of intestinal mucosa cells. The process is energy-dependent (requiring 3 ATP molecules per amino acid absorbed).

Protein Metabolism - Body Protein Dynamic

Body proteins (except collagen) are in a constant state of degradation and resynthesis.
Synthesis is greater than degradation.
Protein required for: growth, replacement of cells, milk production during lactation.
Adult protein requirement: 30-60 g/day (0.8 g/kg body weight/day). Daily requirement depends on factors like age, sex, and lactation.

Protein Metabolism - Nitrogen Utilization

Nitrogen intake: Proteins and nucleoproteins are the primary sources. Protein contains 16g nitrogen per 100g.
Nitrogen output:
- Urine: major route of excretion, includes non-protein nitrogenous compounds (e.g., urea, uric acid, ammonia).
- Stools: digestive juices, shed epithelial cells, and undigested fats.
- Sweat: Urea
- Other: Milk and menstrual fluids, hairs, and nails

Protein Metabolism - Nitrogen Balance

Definition: The quantitative difference between nitrogen intake and output daily in grams.
Three states of nitrogen balance:
- Equilibrium: intake equals output (healthy adults on an adequate diet).
- Positive: intake exceeds output (pregnancy, lactation, recovery from illness, and growth periods).
- Negative: output exceeds intake (wasting diseases, inadequate diet, excessive protein catabolism).

Protein Metabolism - Plasma Amino Acids

Plasma amino acid levels vary throughout the day (circadian changes).
Level depends on nutritional state (fed or post-absorption).
Normal range: 4-8 mg/dL.

Protein Metabolism - Amino Acid Pool Sources

Exogenous sources: Absorbed amino acids from dietary proteins.
Endogenous sources: Synthesized non-essential amino acids.
Tissue catabolism: From breakdown of tissue proteins.

Protein Metabolism - Amino Acid Fate

Protein synthesis: Amino acids are incorporated into proteins (plasma proteins, tissue proteins, enzymes, some hormones).
Synthesis of nitrogenous compounds: Glutathione, purine, and pyrimidine bases.
Ketogenic or glucogenic amino acid metabolism pathways for fuel and energy
Synthesis of other specialized products: certain amino acids produce specific substances (e.g., phenylalanine → adrenaline, tryptophan → serotonin).
Catabolism of amino acids: Produces a-keto acids and urea

Protein Metabolism - Deamination

Definition: Removal of the amino group (NH2) from amino acids in the form of ammonia (NH3).
Site: Liver and kidney.
Types:
- Transamination: Transfer of an amino group from one amino acid to a keto acid, forming a new amino acid and a new keto acid.
- Oxidative deamination: Removal of the amino group from an amino acid while oxidizing it to form a-keto acid and NH3.
- Trans-deamination: Combination of transamination and oxidative deamination.

Protein Metabolism - Enzymes involved in deamination

Transaminases: Enzymes that catalyze transamination reactions.
Pyridoxal phosphate (vitamin B6): Coenzyme of transaminases.
L-Amino acid dehydrogenase: Enzyme acting on L-amino acids (except glutamate), low activity but present in liver and kidney; requiring FMN as coenzyme.
D-Amino acid dehydrogenase (FAD is the coenzyme): Enzyme acts on D amino acids and glycine; present in liver and kidneys

Protein Metabolism - Ammonia Metabolism

Sources: Deamination of amino acids, intestinal bacteria acting on dietary proteins or urea, renal tubular cell's action in cases of acidosis.
Fate: Ammonia is highly toxic, rapidly removed from circulation by the liver.
Pathways:
- Anabolic pathway: Formation of glutamate and other non-essential amino acids, and synthesis of purines and pyrimidines.
- Catabolic pathway: Formation and excretion of glutamine, mainly in the kidneys (by glutaminase).
Urine excretion: The kidney excretes ammonia that accounts of up to 40 % of urinary ammonia.
Urea formation: Ammonia is converted to urea in the urea cycle in the liver.
Urea Cycle: The main process of catabolizing amino acids in the body resulting in urea formation. A 5 step pathway in the liver's mitochondria. Liver is the only site for urea production. 5 enzymes are essential for Urea cycle function.

Protein Metabolism - Factors affecting urea levels

Protein Diet: Increased protein intake leads to increased urea formation.
Liver Disease: Liver's inability to синтезировать urea leads to decreased urea and increased blood ammonia.
Kidney Disease: Inability of the kidney to excrete urea leads to a buildup (increased levels) of urea in the blood.

Protein Metabolism - Urea Cycle Disorders

Defects in the 5 enzymes of the urea cycle can cause hyperammonemia (high blood ammonia levels).
Types include hyperammonemia type I (carbamoyl phosphate synthetase I deficiency), hyperammonemia type II (ornithine transcarbamoylase deficiency), citrullinemia (argininosuccinate synthetase deficiency), argininosuccinic aciduria (argininosuccinase deficiency), and hyperargininemia (arginase deficiency).

Protein Metabolism - Additional Points

Circadian changes in plasma amino acid levels occur throughout the day and are dependent on the nutritional status.

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Description

This quiz tests your knowledge on the urea cycle, including the functions of key enzymes, the activation of carbamoyl phosphate synthetase I, and the consequences of liver disease on urea levels. Ideal for students studying biochemistry and metabolic disorders.