Isoleucine (symbol Ile or I)
Metabolism
Biosynthesis
In plants and microorganisms, isoleucine is synthesized from
Pyruvic acid and alpha-ketobutyrate. This pathway is not present in humans. Enzymes involved in this biosynthesis include:
-
Acetolactate synthase (also known as acetohydroxy acid synthase)
-
Acetohydroxy acid isomeroreductase
-
Dihydroxyacid dehydratase
-
Valine aminotransferase
Catabolism
Isoleucine is both a
glucogenic 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 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.
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.
In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels.
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.
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 adults 19 years and older, 19 mg of isoleucine/kg body weight is required daily.
Beside its biological role as a nutrient, isoleucine also participates in regulation of glucose metabolism.
Genetic diseases can change the consumption requirements of isoleucine. Amino acids cannot be stored in the body. Buildup of excess amino acids will cause a buildup of toxic molecules so, humans have many pathways to degrade each amino acid when the need for protein synthesis has been met.
Many animals and plants are dietary sources of isoleucine as a component of proteins.
Synthesis
Routes to isoleucine are numerous. One common multistep procedure starts from 2-bromobutane and
diethylmalonate.
Synthetic isoleucine was first reported in 1905 by French chemists
Louis 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.
Ehrlich published his own synthesis of isoleucine in 1908.
See also
External links
