Isoleucine (symbolIle orI)[1] is anα-amino acid that is used in thebiosynthesis ofproteins. It contains anα-amino group (which is in the protonated −NH+ 3 form under biological conditions), anα-carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and ahydrocarbon side chain with abranch (a centralcarbon atom bound to three other carbon atoms). It is classified as a non-polar, uncharged (at physiological pH), branched-chain,aliphatic amino acid. It isessential 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.[2] In plants and bacteria, isoleucine is synthesized from apyruvate employing leucine biosynthesis enzymes.[3] It isencoded by thecodons AUU, AUC, and AUA.
In plants and microorganisms, isoleucine is synthesized frompyruvate andalpha-ketobutyrate. This pathway is not present in humans. Enzymes involved in this biosynthesis include:[4]
Isoleucine is both aglucogenic and aketogenic amino acid.[4] After transamination withalpha-ketoglutarate, the carbon skeleton is oxidised and split intopropionyl-CoA andacetyl-CoA. Propionyl-CoA is converted intosuccinyl-CoA, aTCA cycle intermediate which can be converted intooxaloacetate 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 formcitrate or used in the synthesis ofketone bodies (hence ketogenic) orfatty acids.[5]
Isoleucine, like otherbranched-chain amino acids, is associated with insulin resistance: higher levels of isoleucine are observed in the blood of diabetic mice, rats, and humans.[6] 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.[7][8] Reduced dietary levels of isoleucine are required for the beneficial metabolic effects of alow protein diet.[8] In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels.[9] Mice fed a low isoleucine diet are leaner, live longer, and are less frail.[10] In humans, higher dietary levels of isoleucine are associated with greaterbody mass index.[8]
The Food and Nutrition Board (FNB) of the U.S.Institute of Medicine has set Recommended Dietary Allowances (RDAs) foressential amino acids in 2002. For adults 19 years and older, 19 mg of isoleucine/kg body weight is required daily.[11]
Beside its biological role as a nutrient, isoleucine also participates in regulation ofglucose metabolism.[5] Isoleucine is an essential component of many proteins. As an essential amino acid, isoleucine must be ingested or protein production in the cell will be disrupted.Fetal hemoglobin is one of the many proteins that require isoleucine.[12] Isoleucine is present in the gamma chain of fetal hemoglobin and must be present for the protein to form.[12]
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.[13] Mutations in isoleucine-degrading enzymes can lead to dangerous buildup of isoleucine and its toxic derivative. One example ismaple syrup urine disease (MSUD), a disorder that leaves people unable to breakdown isoleucine,valine, andleucine.[14] 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.[15]
Many animals and plants are dietary sources of isoleucine as a component of proteins.[5] Foods that have high amounts of isoleucine includeeggs,soy protein,seaweed, turkey,chicken, lamb,cheese, andfish.
Routes to isoleucine are numerous. One common multistep procedure starts from2-bromobutane anddiethylmalonate.[16] Synthetic isoleucine was first reported in 1905 by French chemistsBouveault and Locquin.[17]
German chemistFelix Ehrlich discovered isoleucine while studying the composition of beet-sugar molasses 1903.[18] 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.[18] Ehrlich published his own synthesis of isoleucine in 1908.[19]
^Joshi V, Joung JG, Fei Z, Jander G (October 2010). "Interdependence of threonine, methionine and isoleucine metabolism in plants: accumulation and transcriptional regulation under abiotic stress".Amino Acids.39 (4):933–947.doi:10.1007/s00726-010-0505-7.PMID20186554.S2CID22641155.
^abLehninger AL, Nelson DL, Cox MM (2000).Lehninger principles of biochemistry (3rd ed.). New York: Worth Publishers.ISBN1-57259-153-6.OCLC42619569.
^abcRajendram R, Preedy VR, Patel VB (2015).Branched chain amino acids in clinical nutrition. Vol. 1. New York, New York: Humana.ISBN978-1-4939-1923-9.OCLC898999904.
^Institute of Medicine. Panel on Macronutrients, Institute of Medicine. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (2005).Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Washington, D.C.: National Academies Press.ISBN0-309-08537-3.OCLC57373786.
^Korman SH (December 2006). "Inborn errors of isoleucine degradation: a review".Molecular Genetics and Metabolism.89 (4):289–299.doi:10.1016/j.ymgme.2006.07.010.PMID16950638.
^Bouvealt L, Locquin R (1905). "Sur la synthése d'une nouvelle leucine".Compt. Rend. (141):115–117.
^abVickery HB, Schmidt CL (October 1931). "The History of the Discovery of the Amino Acids".Chemical Reviews.9 (2):169–318.doi:10.1021/cr60033a001.ISSN0009-2665.
