Chapter 18-1

1. Nitrogen in the Atmosphere and Its Bioavailability

  • Inert Nitrogen: Nitrogen (N₂) is abundant in the atmosphere but is too stable to be used directly in most biochemical processes.

  • Reduced Nitrogen: Vital for life, but requires energy to convert into usable forms (e.g., NH₃). Only certain microorganisms can fix nitrogen into usable forms, like ammonia (NH₃).

2. Amino Groups and Nitrogen Excretion Pathways

  • Amino Group Disposal:

    • When amino acids are broken down, their amino groups must be safely disposed of to avoid toxicity.

    • Figure 18-2: Shows how different organisms handle amino nitrogen:

      • Ammonotelic (e.g., fish): Excrete ammonia directly into water.

      • Ureotelic (e.g., mammals): Convert ammonia into urea to minimize toxicity and water loss.

      • Uricotelic (e.g., birds and reptiles): Excrete nitrogen as uric acid, conserving water.

  • Nitrogen Excretion in Plants:

    • Unlike animals, plants recycle nearly all their amino groups and rarely excrete nitrogen.

Key Terms:

  • Ammonotelic: Organisms excreting nitrogen as ammonia.

  • Ureotelic: Organisms excreting nitrogen as urea.

  • Uricotelic: Organisms excreting nitrogen as uric acid.

3. Key Amino Acids in Nitrogen Transport

  • Important Amino Acids in Nitrogen Metabolism:

    • Glutamate and Glutamine: Serve as collection points for amino groups and convert easily to citric acid cycle intermediates (e.g., α-ketoglutarate).

    • Alanine and Aspartate: Also play major roles; alanine converts to pyruvate, and aspartate to oxaloacetate.

    • Figure 18-2a: Overview of the role of glutamine, glutamate, and alanine in transporting nitrogen in vertebrates.

    • Glutamine: Safely transports ammonia from other tissues to the liver for excretion.

Key Terms:

  • Glutamate: Collects amino groups, converts to α-ketoglutarate.

  • Glutamine: Major nitrogen transporter, safely carries ammonia to the liver.

  • α-Ketoglutarate: A citric acid cycle intermediate receiving amino groups.

4. Conversion of Ammonia for Excretion in Mammals

  • Ammonia Toxicity: Free ammonia is toxic, especially in high concentrations in the brain.

  • Conversion to Urea in the Liver:

    • In mammals, excess ammonia is transported to the liver and converted into urea through the urea cycle, reducing toxicity.

5. Dietary Protein Breakdown into Amino Acids

  • Digestion Process:

    • Dietary proteins are degraded to amino acids in the gastrointestinal tract.

    • Stomach Digestion:

      • Hormone Gastrin: Stimulates the secretion of hydrochloric acid (HCl) and pepsinogen in the stomach.

      • Hydrochloric Acid (HCl): Creates an acidic environment (pH 1-2.5) that denatures proteins, making them accessible to enzymes.

      • Pepsinogen: Inactive form (zymogen) converted to active pepsin in the stomach, initiating protein breakdown.

Figure 18-3a:

  • Stomach Digestive Process: Shows how gastrin, HCl, and pepsin work together to start protein digestion.

Key Terms:

  • Gastrin: Hormone that stimulates HCl and pepsinogen secretion.

  • Pepsin: Enzyme that breaks down proteins in the stomach.

  • Zymogen: Inactive enzyme precursor.

6. Further Protein Digestion in the Small Intestine

  • Neutralization and Enzyme Activation:

    • As stomach contents move to the small intestine, the acidity triggers secretin release.

    • Secretin: Causes the pancreas to release bicarbonate, neutralizing stomach acid and raising pH to about 7.

  • Pancreatic Enzymes:

    • Cholecystokinin: Released in response to peptides, stimulates secretion of pancreatic enzymes (e.g., trypsinogen, chymotrypsinogen).

    • Trypsinogen Activation:

      • Trypsinogen is converted to active trypsin by enteropeptidase.

      • Trypsin then activates other enzymes, continuing protein digestion efficiently.

Figure 18-3b:

  • Pancreatic Enzymes: Shows pancreatic enzyme production, storage in zymogen granules, and secretion into the small intestine.

Key Terms:

  • Secretin: Hormone that stimulates bicarbonate release from the pancreas.

  • Cholecystokinin (CCK): Hormone that stimulates the release of pancreatic enzymes.

  • Trypsinogen/Trypsin: Inactive form of trypsin, activated by enteropeptidase.

7. Absorption and Transport of Amino Acids

  • Amino Acid Absorption:

    • Amino acids are absorbed through the intestinal mucosa and enter the bloodstream, where they are transported to the liver.

    • Figure 18-3c: Shows the movement of amino acids from the small intestine to the liver.

Pyridoxal Phosphate (PLP) and Its Role in Amino Group Transfer

1. Initial Step in Amino Acid Breakdown

- Main Function: The first step in breaking down most amino acids in the liver is removing the α-amino group.

- Enzymes Involved: This step is done by aminotransferases (also known as transaminases).

- Transamination Reaction: The α-amino group of an amino acid is transferred to α-ketoglutarate, resulting in L-glutamate and an α-keto acid (the deaminated form of the amino acid).

- No Net Deamination: Aminotransferases transfer amino groups without losing them, collecting them in the form of L-glutamate.

2. Pyridoxal Phosphate (PLP) as a Coenzyme

- What is PLP?: PLP is the coenzyme form of vitamin B₆ and plays a crucial role in reactions involving amino groups.

- Role in Transamination: PLP is an intermediate carrier of amino groups in transaminase reactions.

- Forms of PLP: PLP has two main forms:

- Pyridoxal Phosphate (aldehyde form) accepts amino groups.

- Pyridoxamine Phosphate (aminated form) donates amino groups to α-keto acids.

3. Mechanism of Action

- Binding to the Enzyme: PLP binds to the enzyme’s active site via a Schiff base (aldimine) linkage with a lysine (Lys) residue.

- Amino Group Transfer: In most PLP-catalyzed reactions, the amino group from the amino acid replaces this lysine linkage.

4. Types of Reactions Catalyzed by PLP

- Versatile Reactions: PLP can facilitate several types of reactions at different carbon positions (α, β, and γ carbons) in amino acids:

- α-Carbon Reactions: Include transamination, racemization (L- to D-amino acids), and decarboxylation.

- Resonance Stabilization: PLP’s structure (an electron sink) allows it to stabilize carbanion intermediates, preventing unstable intermediates from breaking down prematurely.

Key Figures and Concepts:

- Figure 18-4: Shows transamination where amino acids transfer their amino groups to α-ketoglutarate, forming L-glutamate and an α-keto acid.

- Figure 18-5: Illustrates PLP’s role in accepting and donating amino groups through reversible changes.

- Figure 18-6: Details how PLP stabilizes intermediates in various reactions by delocalizing electrons.