Table of contents · 7 sections
Amino acids are the building blocks of proteins, determining their properties and functions. The human body has 20 proteinogenic amino acids, 8 of which are essential. Knowing the classification, properties, and metabolism of amino acids is the foundation of biochemistry and clinical medicine. This article provides a comprehensive systematization with clinical correlations.
General structure of amino acids
All proteinogenic amino acids are α-amino acids with the general formula:
- α-Carbon (chiral, except for glycine) — bonded to 4 groups:
- Amino group (−NH₂)
- Carboxyl group (−COOH)
- Hydrogen atom (−H)
- Side chain (R-group) — determines the properties of the amino acid
At a physiological pH of 7.4, amino acids exist as zwitterions (−NH₃⁺ and −COO⁻). All proteinogenic amino acids are L-isomers.
Classification by R-group properties
| Group | Amino acids | Characteristic |
|---|---|---|
| Non-polar (hydrophobic) | Gly, Ala, Val, Leu, Ile, Pro, Met, Phe, Trp | Located in the interior of globular proteins, stabilizing their structure |
| Polar uncharged | Ser, Thr, Cys, Tyr, Asn, Gln | Form hydrogen bonds, participate in catalysis |
| Positively charged (basic) | Lys, Arg, His | Carry a (+) charge at pH 7.4. His is the only one with a pKa ~6, acting as a buffer at physiological pH |
| Negatively charged (acidic) | Asp, Glu | Carry a (−) charge at pH 7.4. Glutamate is the main excitatory neurotransmitter |
Essential amino acids
8 amino acids are not synthesized in the human body and must be obtained from the diet:
Mnemonic: «PVT TIM HALL» (Phe, Val, Trp, Thr, Ile, Met, His*, Arg*, Leu, Lys)
| Amino acid | One-letter code | Function / deficiency |
|---|---|---|
| Phenylalanine (Phe) | F | Precursor of tyrosine → dopamine, norepinephrine. Defect: phenylketonuria (PKU) |
| Valine (Val) | V | BCAA (branched-chain amino acid) — metabolized in muscles |
| Tryptophan (Trp) | W | Precursor of serotonin and melatonin, NAD⁺ (niacin). Deficiency → pellagra |
| Threonine (Thr) | T | Protein glycosylation, synthesis of mucins |
| Isoleucine (Ile) | I | BCAA, both ketogenic and glucogenic |
| Methionine (Met) | M | Methyl group donor (via SAM), initiating amino acid in translation |
| Leucine (Leu) | L | BCAA, purely ketogenic (along with lysine). mTOR activator |
| Lysine (Lys) | K | Purely ketogenic, hydroxylation → component of collagen |
*His and Arg are conditionally essential (essential in children).
Glucogenic and ketogenic amino acids
- Glucogenic — metabolized to pyruvate or TCA cycle intermediates → can yield glucose (gluconeogenesis). Most amino acids
- Ketogenic — metabolized to acetyl-CoA or acetoacetate → ketone bodies. Only Leu and Lys are purely ketogenic
- Mixed (both gluco- and ketogenic): Ile, Phe, Thr, Trp, Tyr
Mnemonic for ketogenic: «Only Leucine and Lysine are purely Ketogenic» → LL.
Post-translational modifications
- Hydroxylation of proline and lysine (vitamin C!) → collagen. Vitamin C deficiency → scurvy (weak collagen)
- Phosphorylation of serine, threonine, tyrosine → enzyme regulation (kinases/phosphatases)
- Carboxylation of glutamate (vitamin K!) → clotting factors (II, VII, IX, X)
- Methylation of lysine and arginine in histones → regulation of gene expression
- Disulfide bonds between cysteines → stabilization of tertiary structure (immunoglobulins, insulin)
Clinical correlations
| Disease | Defect | Amino acid |
|---|---|---|
| Phenylketonuria (PKU) | Phenylalanine hydroxylase deficiency | ↑ Phe, ↓ Tyr |
| Maple syrup urine disease | Branched-chain α-keto acid dehydrogenase deficiency | ↑ Val, Leu, Ile |
| Homocystinuria | Cystathionine-β-synthase deficiency | ↑ homocysteine, ↓ cysteine |
| Alkaptonuria | Homogentisate oxidase deficiency | ↑ homogentisic acid (from Tyr) |
| Scurvy | Vitamin C deficiency → impaired hydroxylation | Pro, Lys in collagen |
Frequently asked questions
Why are leucine and lysine strictly ketogenic?
Their catabolism yields only acetyl-CoA and/or acetoacetate. Acetyl-CoA cannot be converted to pyruvate or OAA (humans lack the glyoxylate cycle) → cannot yield glucose. All other amino acids are at least partially glucogenic.
Why is newborn screening for PKU necessary?
Phenylketonuria (1:10,000) — without treatment, phenylalanine accumulation causes severe intellectual disability. Early diagnosis (Guthrie test on days 4–5 of life) and a phenylalanine-free diet prevent brain damage. This is one of the most successful examples of neonatal screening.
Study chemistry through interactive lessons on the platform. Related topics: Krebs cycle, mitosis and meiosis, antibiotics. Use clinical calculators for biochemical calculations.