User:Bhnson1/Isoleucine

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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+3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO− 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 our diet. In plants isoleucine can be synthesized from threonine and methionine. In plants and bacteria, Isoleucine is synthesized from pyruvate employing leucine biosynthesis enzymes. It is encoded by the codons AUU, AUC, and AUA.

Biosynthesis
In plants and microorganisms, isoleucine is synthesized via several steps starting from pyruvate and alpha-ketobutyrate. As an essential nutrient, 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. 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 acids.

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 adults 19 years and older, 19 mg of isoleucine/kg body weight is required daily.

Beside its biological role as a nutrient, Isoleucine also has been shown to participate in regulation of glucose metabolism. Isoleucine is an essential component of many proteins. Isoleucine is known to be necessary in the formation of Fetal hemoglobin.

Nutritional sources
There are many animal and plant-based dietary sources of isoleucine. Isoleucine is commonly ingested as a component of proteins. When proteins enter the small intestine they are broken into single amino acids by enzymes known as proteases. Free amino acids are taken up by the lining of the digestive tract, mainly in the small intestine, then used in the body. As an essential component of many proteins, animal and plant based protein sources contain isoleucine. Foods that have high amounts of isoleucine include eggs, soy protein, seaweed, turkey, chicken, lamb, cheese, and fish.

Synthesis and Discovery
There are many possible routes to synthesize Isoleucine. One common multistep procedure starts from 2-bromobutane and diethylmalonate. Synthetic isoleucine was first reported in 1905 by French chemists Bouveault and Locquin.

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.