Summary
Essential amino acids cannot be synthesized by humans and must be obtained from the diet. These nine amino acids have complex biosynthetic pathways in plants and microorganisms, and their metabolism is crucial for protein synthesis, neurotransmitter production, and energy homeostasis.
Key Points
- 1Nine amino acids cannot be synthesized by humans
- 2BCAAs metabolized primarily in muscle, not liver
- 3Methionine is the precursor of the universal methyl donor SAM
- 4Tryptophan is precursor to serotonin and contributes to NAD synthesis
Essential amino acids represent a critical nutritional requirement and intersection between human biochemistry and the metabolic capabilities of other organisms.
The Essential Nine
Humans cannot synthesize these amino acids *de novo*:
| Amino Acid | Abbreviation | Key Features |
|------------|--------------|--------------|
| Histidine | His, H | Conditionally essential in adults |
| Isoleucine | Ile, I | Branched-chain amino acid (BCAA) |
| Leucine | Leu, L | BCAA, mTOR activator |
| Lysine | Lys, K | Often limiting in plant proteins |
| Methionine | Met, M | Sulfur donor, SAM precursor |
| Phenylalanine | Phe, F | Tyrosine precursor |
| Threonine | Thr, T | Glycine precursor |
| Tryptophan | Trp, W | Serotonin precursor, often limiting |
| Valine | Val, V | BCAA |
Mnemonic
PVT TIM HALL: Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine*, Leucine, Lysine
*Arginine is conditionally essential (required during growth/stress)
Branched-Chain Amino Acids (BCAAs)
Leucine, Isoleucine, Valine
The three BCAAs share unique metabolic features:
#### Distinctive Metabolism
- Not metabolized in liver: Unlike other amino acids
- Muscle is primary site: BCAA transaminase and dehydrogenase
- Shared catabolic pathway: First two steps identical
#### Metabolic Pathway
1. Transamination: BCAT produces α-keto acids
2. Oxidative decarboxylation: BCKDH complex (rate-limiting)
3. Divergent pathways: Different end products
#### End Products
- Leucine: Acetyl-CoA, acetoacetate (ketogenic only)
- Isoleucine: Acetyl-CoA, succinyl-CoA (ketogenic + glucogenic)
- Valine: Succinyl-CoA (glucogenic only)
#### Clinical Significance
- Maple Syrup Urine Disease: BCKDH deficiency
- Exercise metabolism: BCAAs as muscle fuel
- mTOR signaling: Leucine activates protein synthesis
Aromatic Amino Acids
Phenylalanine
- Hydroxylation to tyrosine: By phenylalanine hydroxylase (PAH)
- Requires tetrahydrobiopterin (BH4): As cofactor
- Phenylketonuria (PKU): PAH deficiency; requires dietary restriction
Tryptophan
The least abundant essential amino acid:
#### Serotonin Pathway
2. Aromatic amino acid decarboxylase → Serotonin
3. Further to → Melatonin (in pineal gland)
#### Kynurenine Pathway
Sulfur-Containing Amino Acids
Methionine
Central role in one-carbon metabolism:
#### S-Adenosylmethionine (SAM)
- Universal methyl donor: DNA, proteins, lipids, neurotransmitters
#### Transsulfuration Pathway
- Homocysteine + serine → Cysteine
Homocysteine and Disease
Elevated homocysteine associated with:
Lysine and Threonine
Lysine
Unique among amino acids:
- No transamination: Cannot regenerate from α-keto acid
- Saccharopine pathway: Main catabolic route
- Protein quality: Often limiting in cereals
- Carnitine synthesis: Required for fatty acid transport
Threonine
- Glycine generation: Via threonine aldolase
- Mucin synthesis: Important for gut health
- Relatively abundant: In animal proteins
Dietary Considerations
Protein Quality
Defined by essential amino acid content:
- Complete proteins: Contain all essential AAs (meat, eggs, dairy)
- Incomplete proteins: Low in one or more (most plant proteins)
- Complementary proteins: Combining foods (beans + rice)
Limiting Amino Acids
Amino acid in shortest supply relative to requirement:
- Cereals: Lysine limiting
- Legumes: Methionine limiting
- Corn: Tryptophan and lysine limiting
Requirements
Daily requirements vary by:
WHO/FAO recommended intakes exist for each essential amino acid.