Metabolism of Amino Acids Summary

Metabolism of Amino Acid

Instructor: Dr. Gloria Amegatcher

Course: MLAB 205 - Introduction to Biochemistry

Introduction

  • Energy-giving nutrients:

    • Carbohydrates, lipids, and proteins are classified as these nutrients.

    • These nutrients are termed proximate principles of diet.

    • Roles:

    • Carbohydrates and lipids are primarily energy sources.

    • Energy provision is not the main role of amino acid metabolism.

    • Primary functions of amino acids:

      • Synthesize various proteins.

      • Produce specialized non-protein compounds.

Proteins

  • Functions:

    • Perform a wide variety of functions divided into:

    • Static functions: Structural functions.

    • Dynamic functions: Enzymatic, hormonal, and receptor roles.

  • Composition:

    • High molecular weight composed of long chains of alpha amino acids linked by peptide bonds.

    • Elements present: carbon (C), hydrogen (H), oxygen (O), nitrogen (N), with sometimes phosphorus (P) and sulfur (S).

  • Degradation:

    • Upon degradation, proteins release amino acids (AAs).

    • Each amino acid undergoes its own metabolism.

Amino Acids

  • Types:

    • There are 20 naturally occurring amino acids, out of which:

    • 10 can be synthesized by the body, contributing to the amino acid pool.

  • Hydrolysis:

    • Simple proteins yield only alpha amino acids upon hydrolysis.

  • Subgroups of simple proteins:

    • Includes Albumin, Globulin, and Histones.

Classification of Amino Acids

  1. Monoamino monocarboxylic acids

  2. Monoamino dicarboxylic acids

  3. Diamino monocarboxylic acids

  4. Sulfur-containing amino acids

  5. Aromatic amino acids

  6. Heterocyclic amino acids

Sources of Amino Acids

  • Turnover of body protein:

    • Continuous renewal of proteins in the body.

  • Intake of dietary protein:

    • Essential for obtaining amino acids from food.

  • Synthesis of non-essential amino acids (EAs):

    • Derived from digestion of consumed proteins.

    • Released through breakdown of body’s own protein stores, particularly during:

    • Fasting

    • Illness

    • Intensive physical activity.

    • Maintains adequate amino acid levels even when dietary intake is insufficient through internal production from simpler molecules.

Uses of Amino Acids

  • Building blocks for the body's proteins:

    • Amino acids combine to form numerous proteins that structure cells, tissues, and organs (muscles, skin, hair).

  • Creation of specialized molecules:

    • Beyond proteins, amino acids serve other roles.

  • Source of energy:

    • Used for energy when needed.

  • Amino acid pool:

    • Present in plasma and tissues, a dynamic process of continuous addition and removal.

  • Role in neurotransmitter production:

    • Specific amino acids produce brain chemicals such as serotonin and dopamine, which regulate mood, sleep, appetite, and overall brain function.

Pathways of Amino Acid Metabolism

  1. Digestion of dietary proteins

  2. Digestion of body proteins

  3. Endogenous synthesis of amino acids

  4. Synthesis of proteins

  5. Amino acid pool

  6. Synthesis of non-protein compounds

  7. Breakdown into ammonia and carbon skeleton

Essential and Non-Essential Amino Acids

  • Protein Composition:

    • Proteins consist of 20 standard L-amino acids, all vital for protein synthesis.

  • Classification:

    • Essential amino acids (EAA): Cannot be synthesized by the body and must be included in the diet.

    • Non-essential amino acids (NEAA): Can be synthesized internally from simpler molecules.

List of Amino Acids

Essential Amino Acids Include:

  • Histidine (H)

  • Isoleucine (I)

  • Leucine (L)

  • Lysine (K)

  • Methionine (M)

  • Phenylalanine (F)

  • Threonine (T)

  • Valine (V)

  • Tryptophan (W)

  • Conditionally Essential Amino Acids:

    • Arginine (R)

    • Cysteine (C)

    • Glutamine (Q)

    • Glycine (G)

    • Proline (P)

    • Tyrosine (Y)

Non-Essential Amino Acids Include:

  • Alanine (A)

  • Aspartic acid (D)

  • Asparagine (N)

  • Glutamic acid (E)

  • Serine (S)

  • Selenocysteine (U)

  • Pyrrolysine (O)

Urea Cycle

  • Function of Amino Group:

    • The amino group of amino acids forms urea, the key excretory product of protein metabolism.

  • Fate of Carbon Skeletons:

    • Converted to keto acids via transamination:

    • Fates of keto acids include:

      • Energy production.

      • Glucose synthesis.

      • Fat or ketone body formation.

      • Non-essential amino acid production.

Transamination

  • Definition:

    • The transfer of an amino (-NH2) group from an amino acid to a keto acid.

  • Process:

    • Involves interconversion between pairs of amino acids and keto acids.

  • Enzymes:

    • Catalyzed by transaminases requiring pyridoxal phosphate (PLP), which is derived from vitamin B6.

  • Functionality:

    • Redistributes amino groups, produces non-essential amino acids based on cellular demand.

    • Redirects excess amino acids to generate energy and consolidates nitrogen in glutamate.

    • Involves all amino acids except lysine, threonine, proline, and hydroxyproline.

    • Clinical Relevance:

    • Serum transaminases serve as essential diagnostic markers.

Deamination

  • Definition:

    • The removal of the amino group from amino acids as NH3.

  • Types:

    • Can be oxidative or non-oxidative.

    • Oxidative Deamination:

    • Releases free ammonia (NH3) from amino acids via oxidation.

  • Location:

    • Primarily occurs in the liver and kidneys.

  • Purpose:

    • Provides NH3 for urea synthesis and alpha-keto acids for energy and other metabolic reactions.

Urea Synthesis

  • Urea is the end product formed during protein metabolism.

  • Toxicity of Ammonia:

    • Ammonia from amino acid nitrogen poses harmful effects.

  • Detoxification Process:

    • Ammonia is converted to urea for eliminating toxicity.

  • Synthesis Process:

    • Occurs mainly in the liver, with excretion via kidneys.

  • Steps of Urea Formation:

    • Ammonia + CO2 combine to form carbamoyl phosphate.

    • Carbamoyl phosphate enters the cycle to form citrulline.

    • Citrulline combines with another nitrogen source forming arginine.

    • Arginine is subsequently broken down to release urea.

  • Key Point: Urea synthesis effectively removes excess nitrogen, preventing ammonia toxicity.

Urea Cycle Overview

  • Simplified Steps of Urea Synthesis in liver:

    1. Ammonia + CO2 → Carbamoyl phosphate.

    2. Carbamoyl phosphate → Citrulline.

    3. Citrulline + nitrogen source → Arginine.

    4. Arginine breakdown yields Urea.

  • Significance:

    • Converts toxic ammonia into urea for safe excretion by the kidneys, preventing nitrogen overload.

Urea Cycle and Krebs Cycle Connection

  • Link:

    • The urea cycle detoxifies ammonia into urea within the liver and is connected to the Krebs (TCA) cycle through shared intermediates (e.g., fumarate, citrulline).

  • Significance:

    • Integrates nitrogen removal with energy metabolism, emphasizing the importance of both cycles in maintaining homeostasis.