5BICH001W Nitrogen Metabolism 2024 students

Nitrogen Metabolism Overview

  • Study Code: 5BICH001W

  • Focus: Metabolic Biochemistry

Learning Objectives

  • Understand the nitrogen cycle

  • Identify sources of amino acids

  • Grasp amino acid synthesis processes

  • Learn about the transport mechanisms of amino acids

The Nitrogen Cycle and Nitrogen Fixation

  • Human Dependence on Nitrogen:

    • Humans rely on organisms to convert atmospheric N2 into usable forms (NH4+ or NO3-).

  • Inert Nature of Atmospheric Nitrogen:

    • N2 has a triple bond (bond energy: 930 kJ/mol), making it largely unavailable for biological use.

  • Nitrogen Fixation Process:

    • Enzyme complex: Bacterial nitrogenases reduce N2 to NH4+, enabling amino acid production.

Mechanism of Nitrogen Fixation

  • Reaction:

    • N2 + 3H2 → 2NH3 (Atmospheric nitrogen reduced to ammonia)

  • Requirements for Nitrogen Fixation:

    • Enzyme system: Nitrogenase complex

    • Reducing agent: Dinitrogenase reductase

    • Energy source: ATP (16 ATP per N2 reduced)

Overview of Amino Acids

  • Importance of Amino Acids:

    • Building blocks of proteins

    • Precursors for biologically active molecules (neurotransmitters, DNA bases, etc.)

    • Serve as energy sources during prolonged fasting or high protein diets

  • Types of Amino Acids:

    • ~300 types in nature; only 20 as protein builders.

    • Amino Acid Classification:

      • Essential, Nonessential, Conditional

Essential vs. Nonessential Amino Acids

  • Essential Amino Acids:

    • Examples: Valine, Leucine, Methionine, Histidine, Tryptophan

  • Nonessential Amino Acids:

    • Examples: Alanine, Aspartate, Glutamate

  • Conditional Amino Acids:

    • Example: Arginine, Cysteine, Glutamine

Dietary Sources of Amino Acids

  • Animal Sources:

    • Meats, dairy, eggs, fish

  • Vegan Sources:

    • Legumes, pulses, whole grains, nuts, soy products

Digestion and Absorption of Proteins

  • Process in the Stomach:

    • pH 1-2: Proteins are denatured by pepsin

  • Role of Pancreatic Enzymes:

    • Enzymes such as elastase, trypsin, and chymotrypsin break polypeptides into amino acids in the small intestine.

  • Transport and Absorption:

    • Free amino acids and dipeptides are absorbed into the bloodstream.

Amino Acid Composition of Proteins

  • Determining Factors:

    • Size (molecular weight), charge (isoelectric point), hydrophobicity (hydrophilic vs. hydrophobic amino acids)

Amino Acid Biosynthesis

  • Biosynthetic Pathways:

    • Intermediates from glycolysis, citric acid cycle, and pentose phosphate pathway

Amino Acid Synthesis Processes

  • Amination Process:

    • NH4+ + α-ketoglutarate → L-glutamate

  • Transamination Process:

    • Involves transferring an amino group; primarily uses glutamate as a donor

Nitrogen Storage and Turnover

  • Nitrogen Storage:

    • Unlike fats, there's no specific nitrogen reserve in the body; protein intake ~50g/day recommended

  • Protein Turnover:

    • Continuous degradation and resynthesis; varies by protein type

  • Amino Acid Usage:

    • Mostly re-incorporated into new proteins; surplus nitrogen excreted as urea.

Nitrogen Balance

  • Defined as Nitrogen Intake - Nitrogen Loss

  • Positive Nitrogen Balance:

    • Intake > Loss (growth, recovery)

  • Negative Nitrogen Balance:

    • Intake < Loss (malnutrition, illness)

Amino Acid Deficiencies

Kwashiorkor

  • Characteristics:

    • Severe protein-energy malnutrition despite adequate calorie intake

    • Symptoms include edema, irritability, rash, and fatty liver.

Marasmus

  • Characteristics:

    • Severe deficiency of all nutrients; extreme weight loss and muscle wasting.

Fate of Excess Amino Acids

  • Surplus amino acids are not stored; nitrogen is converted to urea.

Transport Mechanisms of Nitrogen

  • Transport Forms:

    • Glutamine and Alanine carry nitrogen to the liver.

  • Urea Cycle:

    • Major pathway for disposal of excess nitrogen, converts toxic ammonia to urea.

Urea Cycle Overview

  • Discovery:

    • Proposed by Hans Krebs in 1932 as the first cyclic metabolic pathway.

  • Key Processes:

    • Involves 5 main steps that convert ammonia into urea for excretion.

Urea Cycle Disorders

  • Disorders result in elevated ammonia levels (hyperammonemia) due to enzyme deficiencies in the cycle.

  • Symptoms:

    • Variable severity; may present as acute or chronic symptoms.

  • Diagnosis and Treatment:

    • Water-soluble solutions, dietary management, and potential liver transplant in severe cases.

Uric Acid and Its Consequences

  • Uric Acid Formation:

    • Product of purine metabolism. High levels can lead to gout, causing painful joint inflammation.

Summary of Nitrogen Metabolism

  • Essential for amino acid and protein synthesis.

  • The nitrogen cycle is crucial for nutrient availability.

  • Urea cycle plays a key role in nitrogen disposal.