Amino Acids and Proteins

Amino Acids

  • Definition: Building blocks of proteins.

  • Role in Proteins:

    • Proteins are long chains of amino acids.

    • The sequence of bases in DNA determines:

    • Amino acid content and arrangement.

    • The sequence of amino acids.

  • Functions:

    • Responsible for growth, maintenance, and repair of all cells.

    • Chemical properties of amino acids determine the biological activity of proteins, which catalyze most reactions within living cells, controlling all cellular processes.

Structure of Amino Acids

  • Composition: Each amino acid contains at least one amino group (H0N) and one carboxyl group (COOH).

  • N-Terminal and C-Terminal Ends:

    • The amino group forms the N-terminal end, while the carboxyl group forms the C-terminal end, both bonded to the alpha-carbon atom.

  • Variability: Variations among amino acids occur in the R groups (side chains) which define the characteristics of each amino acid.

  • Peptide Bonds:

    • Amino group of one amino acid and carboxyl group of another amino acid form a peptide bond.

    • Polypeptide: A chain of amino acids linked by peptide bonds.

    • Protein: A large polypeptide typically composed of approximately 100-150 amino acids.

General Structure of an Alpha Amino Acid

General Structure of an Alpha Amino Acid

  • Formula Components: An amino group (NH₂), a hydrogen atom (H), a carboxyl group (COOH), and an R group which varies among different amino acids.

Table 11-1: Amino Acids Required in the Synthesis of Proteins

  • List of Essential Amino Acids:

    • Glycine (Gly)

    • Alanine (Ala)

    • SERINE (Ser)

    • Valine (Val)

    • Leucine (Leu)

    • Isoleucine (Ile)

    • Threonine (Thr)

    • Methionine (Met)

    • Phenylalanine (Phe)

    • Lysine (Lys)

    • Histidine (His)

    • Tryptophan (Trp)

    • Cysteine (Cys)

    • Proline (Pro)

    • Asparagine (Asn)

    • Aspartate (Asp)

    • Glutamine (Gln)

    • Glutamate (Glu)

Nutritional Considerations

  • Essential Amino Acids: Cannot be synthesized quickly enough in vivo and must be obtained through diet.

    • Diet Sources: Proteins in food are digested by enzymes (e.g., pepsin, trypsin) into amino acids which are then absorbed in the intestine and enter the bloodstream to contribute to the amino acid pool.

  • Non-Essential Amino Acids: The body can synthesize these amino acids sufficiently and they do not require dietary intake.

Metabolism of Amino Acids

  • Overview of Metabolism:

    • Half of the 20 human amino acids necessary for protein synthesis cannot be synthesized rapidly enough, necessitating dietary intake.

  • Enzymatic Process: Breakdown of body proteins occurs to provide energy or synthesize new proteins.

Roles of Amino Acids

  • Protein Synthesis: Includes plasma, intracellular, and structural proteins.

  • Synthesis of Non-Protein Nitrogenous Compounds (NPNs): e.g., purines, pyrimidines, porphyrins, creatine, histamine, thyroxine, epinephrine, and NAD.

    • Proteins must be broken down into amino acids before they can be utilized for energy.

    • Up to 20% of the body's energy requirements are met through amino acid breakdown via the following processes:

    • Deamination: Removal of the amino group from amino acids.

    • Transamination: Transfers the amino group from one amino acid to a keto acid.

    • Glucogenic Amino Acids: Generate glucose precursors such as pyruvate (e.g., alanine).

    • Ketogenic Amino Acids: Degraded to acetyl CoA to form ketone bodies (e.g., lysine and leucine).

Aminoacidopathies

  • Definition: Inherited (inborn) errors of metabolism characterized by an enzyme defect that hinders the body's ability to metabolize certain amino acids, leading to metabolic diseases.

  • Impact: More than 100 diseases identified, often resulting from impaired enzyme activity within a metabolic pathway or defective amino acid transport.

  • Consequences: Leads to accumulation of toxic amino acids or their metabolic by-products, necessitating newborn screening for early diagnosis to enable treatment prior to symptom onset.

  • Example Disorders: PKU, Tyrosinemia, Alkaptonuria, Maple Syrup Urine Disease, Cystinuria.

Screening for Metabolic Disorders

  • Newborn Screening: Essential for early diagnosis of disorders like PKU, with early treatment options providing better outcomes.

Phenylketonuria (PKU)

  • Prevalence: Approximately 1 in 15,000 births.

  • Genetics: Inherited via autosomal recessive pattern.

  • Normal Blood Levels: Phenylalanine concentration should be <120 µmol/L in newborns.

  • Metabolic Dysfunction: Typically associated with a mutation in phenylalanine hydroxylase (PAH) gene, leading to:

    • Classic PKU: Phenylalanine levels >1200 µmol/L.

    • Mild PKU: Partial deficiency, phenylalanine levels of 600-1200 µmol/L.

    • Non-PKU: Mild hyperphenylalaninemia with levels of 180-600 µmol/L without phenylketones' accumulation.

  • Long-term Effects: Chronic high levels can lead to significant and irreversible brain damage. Symptoms may present as a musty odor in metabolites within blood and urine due to toxic accumulation.

Detection and Treatment for PKU

  • Screening Tests: Newborn screening typically performed by detecting elevated phenylalanine levels using:

    • Guthrie Test: Blood filter disk placed on agar to detect inhibition by methionine.

    • HPLC or MS/MS: More precise methods for diagnosing phenylalanine levels.

  • Dietary Management: Requires avoidance of high phenylalanine foods (meat, dairy) while incorporating calculated amounts of cereals, starches, fruits, and vegetables. Recent advancements include a drug called Kuvan that assists with treatment.