Isoleucine (symbol Ile or I) is an
α-amino acid that is used in the
biosynthesis of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s. 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 form under biological conditions), and a
hydrocarbon
In organic chemistry, a hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. Hydrocarbons are examples of group 14 hydrides. Hydrocarbons are generally colourless and hydrophobic, and their odors are usually weak or ...
side chain with a
branch
A branch, sometimes called a ramus in botany, is a woody structural member connected to the central trunk of a tree (or sometimes a shrub). Large branches are known as boughs and small branches are known as twigs. The term '' twig'' usuall ...
(a central
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon ma ...
atom bound to three other carbon atoms). It is classified as a non-polar, uncharged (at physiological pH), branched-chain,
aliphatic
In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane ...
amino acid. It is
essential in humans, meaning the body cannot synthesize it, and must be ingested in our diet. Isoleucine is synthesized from
pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic a ...
employing leucine biosynthesis enzymes in other organisms such as bacteria. It is
encoded by the
codon
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
s AUU, AUC, and AUA.
Metabolism
Biosynthesis
As an essential nutrient, it is not synthesized in the body, hence it must be ingested, usually as a component of proteins. In plants and microorganisms,
it is synthesized via several steps, starting from
pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic a ...
and
alpha-ketobutyrate. Enzymes involved in this biosynthesis include:
#
Acetolactate synthase (also known as acetohydroxy acid synthase)
#
Acetohydroxy acid isomeroreductase
#
Dihydroxyacid dehydratase
The enzyme dihydroxy-acid dehydratase () catalyzes the chemical reaction
:2,3-dihydroxy-3-methylbutanoate \rightleftharpoons 3-methyl-2-oxobutanoate + H2O
This enzyme participates in valine, leucine and isoleucine biosynthesis and pantothenate ...
#
Valine aminotransferase
Catabolism
Isoleucine is both a
glucogenic
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non- carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verteb ...
and a
ketogenic amino acid. After transamination with
alpha-ketoglutarate the carbon skeleton is oxidised and split into
propionyl-CoA and
acetyl-CoA. Propionyl-CoA is converted into
succinyl-CoA, a
TCA cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and prote ...
intermediate which can be converted into
oxaloacetate for gluconeogenesis (hence glucogenic). In mammals acetyl-CoA cannot be converted to carbohydrate but can be either fed into the TCA cycle by condensing with oxaloacetate to form
citrate or used in the synthesis of
ketone bodies (hence ketogenic) or
fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
s.
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. Mice fed an isoleucine deprivation diet for one day have improved insulin sensitivity, and feeding of an isoleucine deprivation diet for one week significantly decreases blood glucose levels. 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.
In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels. In humans, higher dietary levels of isoleucine are associated with greater
body mass index.
Functions and requirement
The Food and Nutrition Board (FNB) of the U.S.
Institute of Medicine has set Recommended Dietary Allowances (RDAs) for
essential amino acids in 2002. For isoleucine, for adults 19 years and older, 19 mg/kg body weight/day is required.
Beside its biological role as a nutrient, Isoleucine also has been shown to participate in regulation of
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
metabolism.
Nutritional sources
Even though this amino acid is not produced in animals, it is stored in high quantities. Foods that have high amounts of isoleucine include
eggs,
soy protein,
seaweed, turkey,
chicken
The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adu ...
, lamb,
cheese, and
fish
Fish are Aquatic animal, aquatic, craniate, gill-bearing animals that lack Limb (anatomy), limbs with Digit (anatomy), digits. Included in this definition are the living hagfish, lampreys, and Chondrichthyes, cartilaginous and bony fish as we ...
.
Isomers
Synthesis
Isoleucine can be synthesized in a multistep procedure starting from
2-bromobutane
2-Bromobutane is an isomer of 1-bromobutane. Both compounds share the molecular formula C4H9Br. 2-Bromobutane is also known as ''sec''-butyl bromide or methylethylbromomethane. Because it contains bromine, a halogen, it is part of a larger class ...
and
diethylmalonate
Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compo ...
. Synthetic isoleucine was originally reported in 1905 by French chemist
Louis Bouveault
Louis Bouveault (11 February 1864 – 5 September 1909) was a French scientist who became professor of organic chemistry at the Faculty of Sciences of the University of Paris.
He is known for the Bouveault aldehyde synthesis and the Bouveault� ...
.
German chemist
Felix Ehrlich
Felix Ehrlich (16 June 1877 in Harriehausen (today incorporated into Bad Gandersheim) – 23 January 1942 in Obernigk near Breslau) was a German chemist and biochemist.
Life and work
Felix Ehrlich studied in Berlin and Munich. After receiving h ...
discovered isoleucine in
hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythroc ...
in 1903.
References
External links
Isoleucine and valine biosynthesis
{{Amino acid metabolism intermediates
Proteinogenic amino acids
Glucogenic amino acids
Ketogenic amino acids
Branched-chain amino acids
Essential amino acids
G