Amino acids

1. Core Structure & Physical Properties

  • Basic Structural Components: Each \alpha-amino acid contains a central \alpha-carbon (\text{C}_\alpha) attached to a carboxyl group (-\text{COOH}), a primary amino group (-\text{NH}_2), a hydrogen atom (-\text{H}), and a distinctive side chain (-\text{R}).

  • Stereochemistry:

    • All 20 standard amino acids except Glycine possess an asymmetric (chiral) \alpha-carbon. Glycine lacks a chiral center because its side chain is a single hydrogen atom (-\text{H}).

    • All amino acids incorporated into mammalian proteins exist strictly in the L-configuration. D-amino acids are found only in bacterial cell walls and certain antibiotics.

  • Buffering Capacity:

    • Low pH (Acidic): The amino group accepts a proton to become positively charged (-\text{NH}_3^+).

    • High pH (Basic): The carboxyl group donates a proton to become negatively charged (-\text{COO}^-).

  • Amino Acid Pool: Approximately 50 g of free amino acids circulate in blood and tissues, replenished by dietary intake, protein turnover, and hepatic synthesis.

  • Nutritional Requirement: Mammals synthesize 10 out of the 20 standard amino acids. Essential amino acids must be obtained through diet. Arginine is conditionally essential for growth and development in children.

2. Classification of the 20 Standard Amino Acids

Class

Amino Acids

Key Features & High-Yield Exam Notes

Nonpolar (Hydrophobic)

Glycine (Gly, G), Alanine (Ala, A), Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I), Methionine (Met, M), Proline (Pro, P), Phenylalanine (Phe, F), Tryptophan (Trp, W)

• Do not gain/lose protons or form hydrogen/ionic bonds. • Cluster in the interior of soluble globular proteins and on the exterior surface of membrane-bound proteins. • Methionine contains a sulfur atom. • Proline, Phenylalanine, Tryptophan contain cyclic side chains.

Polar Uncharged (Hydrophilic)

Serine (Ser, S), Threonine (Thr, T), Tyrosine (Tyr, Y), Asparagine (Asn, N), Glutamine (Gln, Q), Cysteine (Cys, C)

• Readily form hydrogen bonds with water. • Ser, Thr, Tyr contain hydroxyl (-\text{OH}) groups located at enzyme active sites to facilitate catalysis. • Asn, Gln contain carbonyl and amide groups. • Cysteine contains a sulfhydryl (-\text{SH}) thiol group. Two cysteine residues oxidize to form a covalent disulfide bond (cystine), stabilizing tertiary structure (e.g., insulin).

Acidic (Negatively Charged)

Aspartic acid / Aspartate (Asp, D), Glutamic acid / Glutamate (Glu, E)

• Fully ionized at physiological pH to yield negatively charged carboxylate side chains (-\text{COO}^-). • Serve as proton donors.

Basic (Positively Charged)

Lysine (Lys, K), Arginine (Arg, R), Histidine (His, H)

• Side chains accept protons to carry a net positive charge (-\text{NH}^+). • Histidine contains an imidazole ring that buffers blood pH at 7.4 and coordinates oxygen binding in hemoglobin.

3. High-Yield Nonstandard Amino Acids

Nonstandard amino acids are produced via post-translational modifications after incorporation into polypeptide chains:

  • Hydroxyproline & Hydroxylysine:

    • Formed via hydroxylation of Proline and Lysine residues by prolyl and lysyl hydroxylases.

    • Require Vitamin C (Ascorbic Acid) as an essential coenzyme.

    • Crucial for triple-helix stability and cross-linking in collagen.

  • \gamma-Carboxyglutamate:

    • Synthesized exclusively in the liver via \gamma-carboxylation of glutamate residues.

    • Requires Vitamin K as a cofactor.

    • Binds negatively charged membrane phospholipids via positively charged calcium ions (\text{Ca}^{2+}).

    • Essential for blood clotting factors II (Prothrombin), VII, IX, X and osteocalcin.

    • Clinical correlation: Anticoagulants like Coumarin (Warfarin) act as Vitamin K antagonists, inhibiting glutamate carboxylation to reduce clot formation.

  • Desmosine:

    • Composed of four Lysine residues cross-linked together.

    • Provides elasticity to elastin in tissues such as the lungs.

  • N-Methyllysine:

    • Derivative of Lysine found in myosin (contractile muscle protein).

  • Selenocysteine:

    • Cysteine derivative containing selenium, residing in the active sites of enzymes such as glutathione peroxidase, thioredoxin reductase, and iodothyronine deiodinase.

4. Key Chemical Reactions & Derivatives

  • Peptide Bond Formation: Covalent condensation reaction between the \alpha-carboxyl group of one amino acid and the \alpha-amino group of another, eliminating \text{H}_2\text{O} and consuming ATP.

  • Transamination: Reversible transfer of an amino group from an amino acid to an \alpha-keto acid.

  • Deamination: Removal of the amino group as free ammonia (\text{NH}_3), leaving behind a carbon keto acid skeleton.

    • Toxic \text{NH}_3 travels to the liver to enter the urea cycle, converting into non-toxic urea for renal excretion.

  • Decarboxylation: Removal of the carboxyl group as \text{CO}_2 to generate bioactive amines:

    • \text{Histidine} \xrightarrow{\text{decarboxylation}} \text{Histamine}.

  • Synthesis of Catecholamines:

    • Synthesized sequentially from Tyrosine: \text{Tyrosine} \rightarrow \text{L-DOPA} \rightarrow \text{Dopamine} \rightarrow \text{Norepinephrine} \rightarrow \text{Epinephrine}.

  • Synthesis of Creatine:

    • Derived from Glycine and Arginine.

    • Stored as phosphocreatine (95% in skeletal muscle; remainder in cardiac muscle and brain) to rapidly regenerate ATP from ADP during high energy demand.

5. Clinical Diagnostic & Metabolic Highlights

  • Glycation Reactions (Non-Enzymatic):

    • Monosaccharides (primarily glucose) react spontaneously with free -\text{NH}_2 groups on proteins in hyperglycemic states.

    • HbA1c (Glycated Hemoglobin): Reflects average blood glucose levels over 2–3 months (the lifespan of red blood cells).

    • Fructosamine (Glycated Albumin): Reflects average blood glucose control over 2–3 weeks (the lifespan of serum albumin).

  • Metabolic Fate of Carbon Skeletons:

    • Fasting State: Liver converts carbon skeletons into glucose, ketone bodies, and \text{CO}_2.

    • Postprandial State: Liver stores carbon skeletons as glycogen and triglycerides.

    • Untreated Diabetes Mellitus: Accelerated conversion of amino acid carbon skeletons into excess ketone bodies in the liver.