Isoleucine

Chemical structure of L-isoleucine
Isoleucine
Systematic (IUPAC) name
(2S,3S)-2-amino-3-methylpentanoic acid
Identifiers
CAS number	73-32-5
PubChem	791
Chemical data
Formula	C6H13NO2
Mol. weight	131.18
SMILES	CC[C@H](C)[C@H](N)C(O)=O
Complete data

Isoleucine is an α-amino acid that is found in most proteins and is essential in the human diet. Together with threonine, isoleucine is one of two common amino acids that has a chiral side chain; that is, one that is not superimposable on its mirror image.

With a hydrocarbon side chain, Isoleucine is classified as a hydrophobic amino acid. Isoleucine is similar to leucine and valine in being a branched-chain amino acid and whose buildup in the blood and urine, due a particular enzyme deficiency, causes the serious metabolic disorder maple syrup urine disease.

In humans, the L-isomer of isoleucine, which is the only form that is involved in protein synthesis, is one of the 20 standard amino acids common in animal proteins and required for normal functioning in humans. Valine is also classified as an "essential amino acid" since it cannot be synthesized by the human body from other compounds through chemical reactions and thus has to be taken in with the diet.

Isoleucine's three letter code is Ile, its one letter code is I, and its systematic name is 2-amino-3-methylpentanoic acid (IUPAC-IUB 1983).

Structure

In biochemistry, the term amino acid is frequently used to refer specifically to alpha amino acids: those amino acids in which the amino and carboxylate groups are attached to the same carbon, the so-called α–carbon (alpha carbon). The general structure of these alpha amino acids is:

     R
     |
 H2N-C-COOH
     |
     H

where R represents a side chain specific to each amino acid.

Most amino acids occur in two possible optical isomers, called D and L. The L amino acids represent the vast majority of amino acids found in proteins. They are called proteinogenic amino acids. As the name "proteinogenic" (literally, protein building) suggests, these amino acid are encoded by the standard genetic code and participate in the process of protein synthesis.

However, isoleucine, is one of two common amino acids (along with threonine) that has a chiral side chain. Four stereoisomers of isoleucine are possible, including two possible diastereomers of L-isoleucine. However, isoleucine present in nature exists in one specific form, (2S,3S)-2-amino-3-methylpentanoic acid. Only this form is involved in the synthesis of proteins. (A stereoisomer has molecules with the same chemical formula and whose atomic connectivity is the same, but whose atomic arrangement in space is different. A diastereomer are two stereoisomers that are not mirror images of each other.)

Isoleucine's chemical formula is CH₂-CH₃-CH(CH₃)-CH, or more generally C₆H₁₃NO₂ (IUPAC-IUB 1983).

Like leucine and valine, isoleucine has large aliphatic hydrophobic side chains. Its molecules are rigid, and its mutual hydrophobic interactions are important for the correct folding of proteins, as these chains tend to be located inside of the protein molecule.

Isomers of isoleucine

Forms of Isoleucine
Common name:	isoleucine	D-isoleucine	L-isoleucine	DL-isoleucine	allo-D-isoleucine	allo-L-isoleucine	allo-DL-isoleucine
Synonyms:		(R)-Isoleucine	L(+)-Isoleucine	(R*,R*)-isoleucine		alloisoleucine
PubChem:	CID 791	CID 94206	CID 6306	CID 76551
EINECS number:	207-139-8	206-269-2	200-798-2		216-143-9	216-142-3	221-464-2
CAS number:	443-79-8	319-78-8	73-32-5		1509-35-9	1509-34-8	3107-04-8

Dietary aspects

As an essential amino acid, isoleucine is not synthesized in mammals, at least not in sufficient quantities, hence it must be ingested, usually as a component of proteins.

Rich sources of isoleucine are eggs, chicken, pork, mutton, pulses, soya beans, cottage cheese, milk, piyal seeds, cashew nuts, and cereal grains.

Biosynthesis

While isoleucine is not synthesized in animals, in plants and microorganisms isoleucine it is synthesized via several steps starting from pyruvic acid and alpha-ketoglutarate. Enzymes involved in this biosynthesis include (Lehninger 2000):

1. acetolactate synthase
2. acetohydroxy acid isomeroreductase
3. dihydroxyacid dehydratase
4. valine aminotransferase

Isoleucine can be synthesized outside of the body in a multistep procedure starting from 2-bromobutane and diethylmalonate (Marvel 1955). Synthetic isoleucine was originally reported in 1905.

Maple syrup urine disease

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder of amino acid metabolism. It is also called branched chain ketoaciduria.

This amino acid acidopathy is due to a deficiency of the metabolic enzyme branched chain α-keto acid dehydrogenase (BCKDH) leading to a buildup of the branched-chain amino acids isoleucine, leucine, and valine in the blood and urine.

MSUD is characterized by an infant with sweet-smelling urine with an odor similar to that of maple syrup. Infants with this disease seem healthy at birth but if left untreated suffer severe brain damage and eventually die. Because of a genetic bottleneck effect, MSUD has a much higher prevalence in children of Amish and Mennonite descent.

From early infancy, the condition is characterized by poor feeding, vomiting, lack of energy (lethargy), seizures, and mental health issues. The urine of affected infants has a distinctive sweet odor, much like burned caramel, that gives the condition its name.

Treatment of the MSUD, like diabetes, requires careful monitoring of blood chemistry and involves both special diet and frequent testing. A diet with minimal levels of the amino acids isoleucine, leucine, and valine must be maintained in order to prevent neurological damage. Usually patients or parents of patients are assisted by a physician or dietician. This diet must be adhered to strictly and permanently. However, with proper treatment those afflicted are able to live healthy, normal lives and not suffer the severe neurological damage that characterizes the untreated disease.

References

ISBN links support NWE through referral fees

• Doolittle, R. F. 1989. Redundancies in protein sequences. In G. D. Fasman, ed., Prediction of Protein Structures and the Principles of Protein Conformation. New York: Plenum Press. ISBN 0306431319.
• International Union of Pure and Applied Chemistry and International Union of Biochemistry and Molecular Biology (IUPAC-IUB) Joint Commission on Biochemical Nomenclature. 1983. Nomenclature and symbolism for amino acids and peptides: Recommendations on organic & biochemical nomenclature, symbols & terminology. IUPAC-IUB. Retrieved June 14, 2007.
• Lehninger, A. L., D. L. Nelson, and M. M. Cox. 2000. Lehninger Principles of Biochemistry, 3rd ed. New York: Worth Publishing. ISBN 1572591536.
• Marvel, C. S. 1955. dl-Isoleucine. Organic Syntheses, Collected Volume 3: 495.

External links

• Isoleucine and valine biosynthesis. Retrieved June 17, 2007.
• Computational Chemistry Wiki. Retrieved June 17, 2007.

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