thumb|Isoleucine ball and stick model spinning

Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO<sup>−</sup> form under biological conditions), and a hydrocarbon side chain with a branch (a central carbon atom bound to three other carbon atoms). It is classified as a non-polar, uncharged (at physiological pH), branched-chain, aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it. Essential amino acids are necessary in the human diet. In plants isoleucine can be synthesized from threonine and methionine. In plants and bacteria, isoleucine is synthesized from a pyruvate employing leucine biosynthesis enzymes. It is encoded by the codons AUU, AUC, and AUA.

Metabolism

Biosynthesis

In plants and microorganisms, isoleucine is synthesized from pyruvate and alpha-ketobutyrate. This pathway is not present in humans. Enzymes involved in this biosynthesis include:

  1. Acetolactate synthase (also known as acetohydroxy acid synthase)
  2. Acetohydroxy acid isomeroreductase
  3. Dihydroxyacid dehydratase
  4. Valine aminotransferase

Catabolism

Isoleucine is both a glucogenic and a ketogenic amino acid.

Metabolic diseases

The degradation of isoleucine is impaired in the following metabolic diseases:

  • Combined malonic and methylmalonic aciduria (CMAMMA)
  • Maple syrup urine disease (MSUD)
  • Methylmalonic acidemia
  • Propionic acidemia

Insulin resistance

Isoleucine, like other branched-chain amino acids, is associated with insulin resistance: higher levels of isoleucine are observed in the blood of diabetic mice, rats, and humans. In diet-induced obese and insulin resistant mice, a diet with decreased levels of isoleucine (with or without the other branched-chain amino acids) results in reduced adiposity and improved insulin sensitivity. Reduced dietary levels of isoleucine are required for the beneficial metabolic effects of a low protein diet. Mice fed a low isoleucine diet are leaner, live longer, and are less frail. In humans, higher dietary levels of isoleucine are associated with greater body mass index.

Beside its biological role as a nutrient, isoleucine also participates in regulation of glucose metabolism. Isoleucine is present in the gamma chain of fetal hemoglobin and must be present for the protein to form. Mutations in isoleucine-degrading enzymes can lead to dangerous buildup of isoleucine and its toxic derivative. One example is maple syrup urine disease (MSUD), a disorder that leaves people unable to breakdown isoleucine, valine, and leucine. People with MSUD manage their disease by a reduced intake of all three of those amino acids alongside drugs that help excrete built-up toxins.

Many animals and plants are dietary sources of isoleucine as a component of proteins. Synthetic isoleucine was first reported in 1905 by French chemists Bouveault and Locquin.

Discovery

German chemist Felix Ehrlich discovered isoleucine while studying the composition of beet-sugar molasses 1903. In 1907 Ehrlich carried out further studies on fibrin, egg albumin, gluten, and beef muscle in 1907. These studies verified the natural composition of isoleucine.

See also

  • Alloisoleucine, the diasteromer of isoleucine
  • Low Isoleucine protein foods

References

  • Isoleucine degradation
  • Isoleucine biosynthesis