Essential Amino Acids and Proteins

Essential Amino Acids - The VIP Building Blocks

• Indispensable dietary AAs; body cannot synthesize them de novo sufficiently for growth/maintenance.
• 📌 Mnemonic: PVT TIM HALL
  • Phenylalanine, Valine, Threonine
  • Tryptophan, Isoleucine, Methionine
  • Histidine (essential, esp. infants, uremia)
  • Arginine (conditionally essential: trauma, sepsis)
  • Leucine, Lysine
• Metabolic Fates:
  • Purely Ketogenic: Leucine, Lysine.
  • Both Glucogenic & Ketogenic: Phenylalanine, Isoleucine, Tryptophan, Threonine.
• Vital for protein synthesis, N-balance, biomolecule precursors.
• 

⭐ Maple Syrup Urine Disease (MSUD): Autosomal recessive; deficient branched-chain α-ketoacid dehydrogenase. Affects Leucine, Isoleucine, Valine (LIV).

Protein Structure - From Chains to Shapes

• Primary (1°): Amino acid sequence; peptide bonds. Determines final protein shape.
• Secondary (2°): Local folding (α-helix, β-sheet) via backbone H-bonds.
  • α-helix: Right-handed coil. H-bonds between C=O ($n$) & N-H ($n+4$). 📌 Proline: helix breaker.
  • β-sheet: Extended strands, H-bonded (parallel/antiparallel).
• Tertiary (3°): Overall 3D shape of one polypeptide. Interactions: disulfide, hydrophobic, ionic, H-bonds.
• Quaternary (4°): Arrangement of multiple subunits (e.g., Hemoglobin).

⭐ Denaturation (heat, pH, chemicals) disrupts 2°, 3°, 4° structures, sparing 1° (peptide bonds).

Protein Functions & Metabolism - The Body's Workhorses

• Functions:
  • Structural: Collagen (connective tissue), keratin (hair/nails)
  • Enzymatic: Catalysts (pepsin, DNA polymerase)
  • Transport: Hemoglobin (O₂), albumin (fatty acids, drugs), transferrin (Fe³⁺)
  • Immune Defense: Antibodies (immunoglobulins)
  • Hormonal Regulation: Insulin, glucagon, GH
  • Movement: Contractile (actin, myosin)
  • Acid-Base Balance: Buffers (hemoglobin)
  • Receptors/Channels: Membrane proteins
• Metabolism:
  • Digestion:
    • Stomach: Pepsinogen → Pepsin (HCl)
    • Small Intestine: Pancreatic (trypsin) & brush border enzymes
  • Absorption: Active transport of AAs, di/tripeptides
  • Nitrogen Balance: Reflects body protein status.
    • Positive (N intake > N excretion): Growth, pregnancy.
    • Negative (N intake < N excretion): Starvation, trauma.
  • Amino Acid Pool: ~100g free AAs; sources (diet, breakdown), fates (synthesis, energy).
  • Urea Cycle (Liver): Converts toxic $NH_3$ from AA catabolism to urea for renal excretion.

    ⭐ Ornithine Transcarbamylase (OTC) deficiency: most common urea cycle disorder (X-linked). Hyperammonemia, encephalopathy.

Nutritional Aspects & Disorders - Fueling & Failing

• Protein Quality Metrics:
  • Nitrogen Balance: $N_{in} - (UUN + \textbf{4g})$. Positive (anabolism), Negative (catabolism).
  • Biological Value (BV): (N retained / N absorbed) × 100. Egg protein BV ≈ \textbf{100}.
  • Net Protein Utilization (NPU): BV × Digestibility Coefficient.
  • Protein Efficiency Ratio (PER): Weight gain (g) / Protein intake (g).
• Protein-Energy Malnutrition (PEM):
  • Kwashiorkor ("sickness of weaning child"): ↓ Protein > ↓ Energy. Edema, hypoalbuminemia, fatty liver, dermatosis (flaky paint), hair (flag sign).
  • Marasmus ("dying away"): ↓ Energy > ↓ Protein. Severe wasting, "old man" face, alert & irritable. No edema.
  • Markers: ↓ Serum albumin, ↓ prealbumin (transthyretin - T½ \textbf{2-3 days}).
• Selected Aminoacidopathies (Metabolic Failure):
  • PKU: ↓ Phenylalanine hydroxylase. Mousy odor. Guthrie test.
  • MSUD: ↓ Branched-chain α-ketoacid dehydrogenase. Burnt sugar urine odor.
  • Alkaptonuria: ↓ Homogentisate oxidase. Dark urine, ochronosis.
  • Homocystinuria: ↓ Cystathionine β-synthase. Lens (↓ & in), Marfanoid, thrombosis.

⭐ > In Kwashiorkor, edema is primarily due to hypoalbuminemia leading to decreased plasma oncotic pressure.

High‑Yield Points - ⚡ Biggest Takeaways

• Essential amino acids (PVT TIM HALL) must be obtained from diet; Arginine & Histidine are semi-essential.
• Kwashiorkor (protein deficiency, edema) vs. Marasmus (calorie & protein deficiency, wasting).
• Phenylketonuria (PKU): phenylalanine hydroxylase deficiency; musty odor, CNS symptoms.
• Maple Syrup Urine Disease (MSUD): deficiency of branched-chain α-ketoacid dehydrogenase.
• Alkaptonuria: homogentisate oxidase defect; ochronosis, black urine on standing.
• Biological Value (BV) & NPU measure protein quality; positive nitrogen balance indicates anabolism_._