Amino acids

Amino acids (aminocarboxylic acids, formerly: amido acids) are the building blocks of proteins. They are released again when proteins are broken down (proteolysis).
Essential amino acids must therefore be taken in with food because the body cannot produce them itself.

• α-amino acids: the amino group on the Cα atom is directly adjacent to the terminal carboxy group.
  • D-amino acids: α-amino acids whose carboxy group (-COOH) and amino group (-NH2) are in D-configuration.
  • L-amino acids: mirror image isomers of D-amino acids, rarer than D-amino acids
  • All proteinogenic amino acids are α-amino acids:
    • Alanine
    • Arginine
    • Asparagine
    • Aspartic acid (aspartate)
    • Cysteine
    • Glutamine (metabolite of glutamate)
    • Glutamic acid
    • Glycine (here more about Glycine as a neurotransmitter)
    • Histidine
    • Isoleucine
    • Leucine
    • Lysine
    • Methionine
    • Phenylalanine (prodrug of dopamine and noradrenaline, prodrug and metabolite of tyrosine)
    • Proline
    • Selenocysteine
    • Serine
    • Threonine
    • Tryptophan (prodrug of serotonin)
    • Tyrosine (prodrug of dopamine and noradrenaline, prodrug and metabolite of phenylalanine)
    • Valine
• β-amino acids (3-aminocarboxylic acids): the amino group is located on the third carbon atom (including the carboxy carbon atom), e.g. β-alanine.
• γ-Amino acids (4-aminocarboxylic acids): the amino group is located on the fourth carbon atom (including the carboxy carbon atom), e.g. γ-aminobutyric acid (GABA) (here more about GABA as a neurotransmitter).

In addition to the 23 proteinogenic amino acids (21 in humans), over 400 non-proteinogenic, naturally occurring amino acids are known to have biological functions. There are also a large number of synthetically produced amino acids. Examples of non-proteinogenic natural amino acids:

• Hydroxyproline (metabolite of proline, essential component of collagen)
• Taurine (conditionally essential) (here more about Taurine for ADHD)
• Citrulline (prodrug of arginine)
• Ornithine (metabolite of arginine, involved in the conversion of ammonia to urea, a key detoxification process)
• Phosphoserine (O-phosphorylated form of serine, prodrug for phosphatidylserine, a phospholipid of the cell membrane of nerve cells)

Proteins are formed from α-amino acids, which are linked together in chains to form polymers by the carboxy group of one amino acid forming a peptide bond with the amino group of the next. The amino acids differ in their side chains and together determine the form in which the polypeptide unfolds into the native protein in an aqueous environment. This biosynthesis of proteins takes place on the ribosomes of all cells using the genetic information of the mRNA.
The mRNA base sequence encodes the amino acid sequence in triplets. Each base triplet represents a codon that stands for a specific proteinogenic amino acid. These proteinogenic amino acids in a specific Order of priority form the proteins.

Some amino acids also act as neurotransmitters (e.g. γ-aminobutyric acid, GABA), hormones or tissue mediators.

Changes in amino acid metabolism have been described in ADHD. However, the amino acids that are relevant for dopamine, noradrenaline and serotonin synthesis in particular are unchanged.

• reduced
  • Histidine¹ (29 % reduced)²
  • Glutamine (10 % reduced)²
  • Proline (20 % reduced)²
  • Isoleucine
    • reduced¹
    • unchanged²
• increased
  • Aspartic acid (aspartate) (increased by 7 %)², tends to be elevated (just not significant) ²
  • Glutamate (increased by 7 %)²
  • Hydroxyproline (increased by 42 %)²
• unchanged
  • Tyrosine
    • unchanged³²
    • reduced (small, older study)¹
  • Tryptophan
    • unchanged³²
    • reduced (small, older study)¹
    • the transport of tryptophan across fibroplast membranes of boys with ADHD was reduced in vitro. This indicates a reduced tryptophan uptake through the blood-brain barrier,⁴
      • However, tryptophan administration did not influence the ADHD symptoms.⁵
      • Tryptophan reduction:
        • Impulsiveness
          • reduced⁶
          • contradictory results⁷
        • reactive aggressiveness⁷
          • reduced in ADHD and increased reactive aggression in controls⁶
          • increased with ADHD⁸
        • ADHD symptoms:
          • barely investigated⁷
          • no improvement observed⁹
          • Attention: deteriorated¹⁰
          • verbal declarative memory: unchanged¹¹
  • Phenylalanine
    • unchanged³²
    • reduced (small, older study)¹
  • Alanine
    • tends to be slightly increased (clearly not significant) ²
    • the transport of alanine across fibroplast membranes of boys with ADHD was increased in vitro. This indicates an increased uptake of alanine through the blood-brain barrier,⁴
  • Arginine²
  • Asparagine²
  • Glycine tends to be minimally reduced (clearly not significant) ²
  • Serine²
  • Taurine tends to be slightly elevated (clearly not significant) ²
  • Citrulline tends to be minimally reduced (clearly not significant) ²
  • Ornithine²
  • Phosphoserine tends to be slightly reduced (clearly not significant) ²
  • Leucine²
  • Lysine tends to be slightly reduced (clearly not significant) ²
  • Methionine tends to be slightly reduced (clearly not significant) ²
  • Threonine tends to be minimally elevated (clearly not significant) ²
  • Valine²
• unclear / contradictory
  • Homocysteine
    • reduces¹² (non-proteinogenic amino acid, metabolic product of methionine)
    • increased homocysteine levels in ADHD correlated with increased hyperactivity/impulsivity¹³
      • A deficiency of folic acid, vitamin B2, B6 and/or B12 can cause an excess of homocysteine.¹⁴ Elevated homocysteine levels can have a neurotoxic effect.
    • unchanged in children with ADHD¹⁵

Elevated ammonia and lactate levels in children with ADHD indicate an involvement of energy metabolism.¹⁶