John E. McMurry et al. - Fundamentals of General, Organic and Biological Chemistry in SI Units Chapter 25

Overview of Protein and Amino Acid Metabolism

Contents Overview

• 25.1 Digestion of Proteins

• 25.2 Amino Acid Metabolism: An Overview

• 25.3 Amino Acid Catabolism: The Amino Group

• 25.4 The Urea Cycle

• 25.5 Amino Acid Catabolism: The Carbon Atoms

• 25.6 Biosynthesis of Nonessential Amino Acids

Essential Nutrients

• Definition: Essential nutrients are molecules that the body requires for optimal functioning but cannot synthesize internally, which necessitates their acquisition through dietary sources.

• Essential Amino Acids: There are nine specific amino acids that are indispensable and must be obtained strictly through diet. These include:

  • Histidine: Vital for growth and tissue repair.

  • Lysine: Crucial for protein synthesis, hormone regulation, and calcium absorption.

  • Isoleucine: Important for muscle metabolism and is heavily concentrated in muscle tissue.

• Health Impacts of Deficiency: A lack of essential amino acids can lead to severe health consequences, including:

  • Anemia: Often resulting from a deficiency in lysine which affects hemoglobin production.

  • Kidney Disease: Might arise due to imbalances in amino acid processing.

  • Mental Health Issues: Insufficiency in certain amino acids can manifest in serious psychological disorders, including psychotic behavior and schizophrenia.

• Case Study: Research indicates that histidine deficiency may exacerbate symptoms of rheumatoid arthritis (RA), highlighting the need for sufficient dietary intake.

Digestion of Proteins

Learning Objectives

• List key steps in the digestion of proteins.

Stepwise Breakdown of Protein Digestion

1. Initial Processing: The digestion of proteins begins in the mouth where chewing mechanically breaks down food into smaller fragments, making it easier for enzymes to act.

2. Stomach: Once swallowed, the food enters the stomach where it is mixed with gastric juices.

• Pepsinogen is activated to pepsin by hydrochloric acid (HCl) in this acidic environment.

• Pepsin plays a pivotal role in beginning the hydrolysis of peptide bonds, yielding smaller polypeptides.

3. Small Intestine: The partially digested proteins are then moved to the small intestine, where:

   • Pancreatic proteases (such as trypsin and chymotrypsin) are secreted in their inactive forms and are activated within the intestinal lumen.

   • They further break down polypeptides into individual amino acids and smaller peptides that can be absorbed.

4. Absorption: Through the process of active transport, amino acids are absorbed across the intestinal lining into the bloodstream where they enter general circulation.

Key Points on Amide Hydrolysis

• Hydrolysis of peptide bonds, which are amide bonds, results in the production of free amino acids that are available for absorption and use by the body.

Protein Hydrolysis Mechanism

• Pepsin initiates the breakdown of protein in the acidic environment of the stomach.

• Pancreatic proteases operate effectively in the neutral pH of the small intestine, ensuring complete protein digestion.

• Transport Systems: Specialized transport systems facilitate the absorption of amino acids; an excess of any single amino acid can lead to imbalances.

Amino Acid Metabolism: Overview

Learning Objectives

• Define the amino acid pool and its role in metabolism.

• Explain processes involved in amino acid catabolism.

Key Concepts

• Amino Acid Pool: This pool consists of free amino acids in the body derived from dietary intake, protein breakdown, and de novo synthesis. It is vital to maintain a balance for normal physiological functions.

• Turnover: Proteins undergo continuous turnover involving breakdown and synthesis; approximately 300 grams of protein is turned over daily in adults, underscoring the dynamic nature of metabolism.

Amino Acid Catabolism Overview

• Amino Group Removal: The catabolism involves a transamination process where amino groups are removed from amino acids.

• Urea Cycle: This cycle is critical for converting amino group nitrogen into urea, which is then excreted by the kidneys, preventing toxic accumulation.

• Organic Acids: Following transamination, the remaining carbon skeletons can enter metabolic pathways such as the citric acid cycle, contributing to energy production and gluconeogenesis.

Significance of Nitrogen-Containing Compounds

• The body does not store nitrogen; instead, it actively manages nitrogen through the urea cycle or synthesis of vital nitrogenous compounds.

• Examples: These compounds include hormones (like insulin), neurotransmitters (such as serotonin), heme (part of hemoglobin), and nucleobases (purines and pyrimidines).

The Amino Group in Catabolism

Learning Objective

• Discuss the fate of nitrogen in amino acid metabolism.

Transamination Process

• The process involves enzymatic interchange wherein an amino group from one amino acid is transferred to a keto acid, facilitated by key enzymes known as transaminases (or aminotransferases).

Oxidative Deamination

• In this step, glutamate loses its amino group, facilitating entry into the urea cycle to eliminate nitrogen waste effectively.

Nitrogen Pathway to Urea

• Oxidative Deamination culminates in the elimination of ammonium ions. A detailed, step-by-step ammonia conversion pathway illustrates the process leading to urea formation.

The Urea Cycle

Learning Objective

• Identify the components and functions of the urea cycle.

Urea Cycle Overview

• Key Reactants include ammonium ions and bicarbonate, which combine to form carbamoyl phosphate.

• Process Steps:

  1. Formation of Citrulline: Catalyzed by carbamoyl phosphate and ornithine.

  2. Creation of Argininosuccinate: Involves citrulline and aspartate.

  3. Cleavage: The cleavage of argininosuccinate gives rise to arginine and fumarate.

  4. Hydrolysis: Finally, arginine is hydrolyzed back to form urea and regenerate ornithine for another turn of the cycle.

Energy Consumption in the Urea Cycle

• The total energy investment includes the hydrolysis of ATP, which is essential for transforming ammonia into a less toxic form (urea).

• Abnormal function of urea cycle enzymes can result in hyperammonemia, a critical condition that often requires dietary management to control nitrogen levels in the body.

Impacts of Uric Acid

• Uncontrolled levels of uric acid can lead to gout, a painful condition characterized by inflammation and swelling in joints.

• Contributing factors to elevated uric acid levels include certain dietary choices (high in purines) and various physiological conditions.

Fate of Carbon Atoms from Amino Acids

Learning Objective

• Describe the metabolic fates of carbon derived from amino acids.

Carbon Pathways

• The carbon skeletons of amino acids can convert into various metabolic intermediates, such as pyruvate or components involved in the citric acid cycle.

Classification of Amino Acids

• Glucogenic: Amino acids that can be converted into glucose through gluconeogenesis.

• Ketogenic: These yield ketone bodies that can serve as alternative energy sources during periods of low carbohydrate intake.

Nonessential Amino Acids

Learning Objective

• Differentiate between essential and nonessential amino acids.

Synthesis of Nonessential Amino Acids

• Humans possess the capability to synthesize roughly half of the 20 amino acids, which are deemed nonessential, meaning they do not need to be replenished through diet.

• Essential amino acids must be sourced from diet due to their complex biosynthesis pathways in organisms.

• Phenylketonuria (PKU) is a metabolic disorder that illustrates the necessity for dietary management of phenylalanine due to its toxic accumulation in individuals lacking the enzyme to metabolize it.

Complementary Proteins and Metabolite Roles

• Incorporating complementary sources of incomplete protein (like beans with rice) can ensure that individuals, particularly vegetarians, intake all essential amino acids necessary for health maintenance.

Summary of Amino Acid Functions

• Essential Amino Acids are critical for a variety of biological roles, including but not limited to protein synthesis, hormone production, and immune function, thus ensuring overall health is preserved.

• Classifying essential amino acids reliance on their dietary sources and their functional roles during various metabolic processes is key to understanding their importance for human health.