Isoleucine

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l-Isoleucine
L-Isoleucin - L-Isoleucine.svg
skeletal formula of L-isoleucine
Ball-and-stick model of L-isoleucine Isoleucine-from-xtal-3D-bs-17.png
Ball-and-stick model of L-isoleucine
Space-filling model of L-isoleucine Isoleucine-from-xtal-3D-sf.png
Space-filling model of L-isoleucine
Names
IUPAC name
Isoleucine
Other names
(2S,3S)-2-amino-3-methylpentanoic acid
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
DrugBank
ECHA InfoCard 100.000.726 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m0/s1 Yes check.svgY
    Key: AGPKZVBTJJNPAG-WHFBIAKZSA-N Yes check.svgY
  • InChI=1/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m0/s1
    Key: AGPKZVBTJJNPAG-WHFBIAKZBB
  • CC[C@H](C)[C@@H](C(=O)O)N
  • Zwitterion:CC[C@H](C)[C@@H](C(=O)[O-])[NH3+]
Properties
C6H13NO2
Molar mass 131.175 g·mol−1
−84.9·10−6 cm3/mol
Supplementary data page
Isoleucine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Isoleucine (symbol Ile or I) [1] 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, and must be ingested in our diet. Isoleucine is synthesized from pyruvate employing leucine biosynthesis enzymes in other organisms such as bacteria. [2] It is encoded by the codons AUU, AUC, and AUA.

Contents

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 and alpha-ketobutyrate. Enzymes involved in this biosynthesis include: [3]

  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. [4]

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. [5] 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. [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 a low protein diet. [8] In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels. [9] In humans, higher dietary levels of isoleucine are associated with greater body mass index. [8]

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. [10]

Beside its biological role as a nutrient, Isoleucine also has been shown to participate in regulation of glucose metabolism. [11]

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, lamb, cheese, and fish. [12]

Isomers

Forms of Isoleucine
Common name :isoleucined-isoleucinel-isoleucinedl-isoleucined-alloisoleucinel-alloisoleucinedl-alloisoleucine
Synonyms:(R)-IsoleucineL(+)-Isoleucine(R*,R*)-isoleucinealloisoleucine
PubChem : CID 791 from PubChem CID 94206 from PubChem CID 6306 from PubChem CID 76551 from PubChem
EINECS number : 207-139-8 206-269-2 200-798-2 216-143-9 216-142-3 221-464-2
CAS number :443-79-8319-78-873-32-51509-35-91509-34-83107-04-8
L-Isoleucin - L-Isoleucine.svg   D-isoleucine.svg
l-isoleucine (2S,3S) and d-isoleucine (2R,3R)
L-alloisoleucine.svg   D-alloisoleucine.svg
l-alloisoleucine (2S,3R) and d-alloisoleucine (2R,3S)

Synthesis

Isoleucine can be synthesized in a multistep procedure starting from 2-bromobutane and diethylmalonate. [13] Synthetic isoleucine was originally reported in 1905 by French chemist Louis Bouveault. [14]

German chemist Felix Ehrlich discovered isoleucine in hemoglobin in 1903.

Related Research Articles

Methionine Sulfur-containing amino acid

Methionine is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical role in the metabolism and health of many species, including humans. It is encoded by the codon AUG.

Alanine Α-amino acid that is used in the biosynthesis of proteins

Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side chain. Consequently, its IUPAC systematic name is 2-aminopropanoic acid, and it is classified as a nonpolar, aliphatic α-amino acid. Under biological conditions, it exists in its zwitterionic form with its amine group protonated (as −NH3+) and its carboxyl group deprotonated (as −CO2). It is non-essential to humans as it can be synthesised metabolically and does not need to be present in the diet. It is encoded by all codons starting with GC (GCU, GCC, GCA, and GCG).

Leucine Chemical compound

Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO form under biological conditions), and a side chain isobutyl group, making it a non-polar aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Human dietary sources are foods that contain protein, such as meats, dairy products, soy products, and beans and other legumes. It is encoded by the codons UUA, UUG, CUU, CUC, CUA, and CUG.

Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO form under biological conditions), and a side chain isopropyl group, making it a non-polar aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Human dietary sources are foods that contain protein, such as meats, dairy products, soy products, beans and legumes. It is encoded by all codons starting with GU (GUU, GUC, GUA, and GUG).

Acetyl-CoA Chemical compound

Acetyl-CoA is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle to be oxidized for energy production. Coenzyme A consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid (B5) through an amide linkage and 3'-phosphorylated ADP. The acetyl group of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol).

Anabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-down aspect. Anabolism is usually synonymous with biosynthesis.

Gluconeogenesis Biological formation of glucose

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 vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise.

Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms.

A low-protein diet is a diet in which people decrease their intake of protein. A low-protein diet is used as a therapy for inherited metabolic disorders, such as phenylketonuria and homocystinuria, and can also be used to treat kidney or liver disease. Low protein consumption appears to reduce the risk of bone breakage, presumably through changes in calcium homeostasis. Consequently, there is no uniform definition of what constitutes low-protein, because the amount and composition of protein for an individual with phenylketonuria would differ substantially from one with homocystinuria or tyrosinemia.

Maple syrup urine disease Autosomal recessive metabolic disorder

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine and earwax, particularly prior to diagnosis and during times of acute illness.

In biochemistry, lipogenesis is the conversion of fatty acids and glycerol into fats, or a metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipogenesis encompasses both fatty acid and triglyceride synthesis, with the latter being the process by which fatty acids are esterified to glycerol before being packaged into very-low-density lipoprotein (VLDL). Fatty acids are produced in the cytoplasm of cells by repeatedly adding two-carbon units to acetyl-CoA. Triacylglycerol synthesis, on the other hand, occurs in the endoplasmic reticulum membrane of cells by bonding three fatty acid molecules to a glycerol molecule. Both processes take place mainly in liver and adipose tissue. Nevertheless, it also occurs to some extent in other tissues such as the gut and kidney. A review on lipogenes in the brain was published in 2008 by Lopez and Vidal-Puig. After being packaged into VLDL in the liver, the resulting lipoprotein is then secreted directly into the blood for delivery to peripheral tissues.

Branched-chain amino acid

A branched-chain amino acid (BCAA) is an amino acid having an aliphatic side-chain with a branch. Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine, and valine. Non-proteinogenic BCAAs include 2-aminoisobutyric acid.

De novo synthesis refers to the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to recycling after partial degradation. For example, nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as formate and aspartate. Methionine, on the other hand, is needed in the diet because while it can be degraded to and then regenerated from homocysteine, it cannot be synthesized de novo.

Amino acid synthesis

Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can only synthesize 11 of the 20 standard amino acids, and in time of accelerated growth, histidine can be considered an essential amino acid.

In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway. The glycolytic pathway also provides the glycerol with which three fatty acids can combine to form triglycerides, the final product of the lipogenic process. When only two fatty acids combine with glycerol and the third alcohol group is phosphorylated with a group such as phosphatidylcholine, a phospholipid is formed. Phospholipids form the bulk of the lipid bilayers that make up cell membranes and surrounds the organelles within the cells.

Acetolactate synthase Class of enzymes

The acetolactate synthase (ALS) enzyme is a protein found in plants and micro-organisms. ALS catalyzes the first step in the synthesis of the branched-chain amino acids.

Glucogenic amino acid

A glucogenic amino acid is an amino acid that can be converted into glucose through gluconeogenesis. This is in contrast to the ketogenic amino acids, which are converted into ketone bodies.

Ketogenic amino acid Type of amino acid

A ketogenic amino acid is an amino acid that can be degraded directly into acetyl-CoA, which is the precursor of ketone bodies and myelin, particularly during early childhood, when the developing brain requires high rates of myelin synthesis. This is in contrast to the glucogenic amino acids, which are converted into glucose. Ketogenic amino acids are unable to be converted to glucose as both carbon atoms in the ketone body are ultimately degraded to carbon dioxide in the citric acid cycle.

FGF21 Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 21 is a protein that in mammals is encoded by the FGF21 gene. The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family and specifically a member of the endocrine subfamily which includes FGF23 and FGF15/19. FGF21 is the primary endogenous agonist of the FGF21 receptor, which is composed of the co-receptors FGF receptor 1 and β-Klotho. Loss of β-Klotho abolishes all effects of FGF21.

The stable isotope composition of amino acids refers to the abundance of heavy and light non-radioactive isotopes of carbon, nitrogen, and other elements within these molecules. Amino acids are the building blocks of proteins. They are synthesized from alpha-keto acid precursors that are in turn intermediates of several different pathways in central metabolism. Carbon skeletons from these diverse sources are further modified before transamination, the addition of an amino group that completes amino acid biosynthesis. Bonds to heavy isotopes are stronger than bonds to light isotopes, making reactions involving heavier isotopes proceed slightly slower in most cases. This phenomenon, known as a kinetic isotope effect, gives rise to isotopic differences between reactants and products that can be detected using isotope ratio mass spectrometry. Amino acids are synthesized via a variety of pathways with reactions containing different, unknown isotope effects. Because of this, the 13C content of amino acid carbon skeletons varies considerably between the amino acids. There is also an isotope effect associated with transamination, which is apparent from the abundance of 15N in some amino acids.

References

  1. "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Retrieved 5 March 2018.
  2. Kisumi M, Komatsubara S, Chibata I (July 1977). "Pathway for isoleucine formation form pyruvate by leucine biosynthetic enzymes in leucine-accumulating isoleucine revertants of Serratia marcescens". Journal of Biochemistry. 82 (1): 95–103. doi:10.1093/oxfordjournals.jbchem.a131698. PMID   142769.
  3. Nelson DL, Cox MM (2000). Lehninger, Principles of Biochemistry (3rd ed.). New York: Worth Publishing. ISBN   1-57259-153-6.
  4. Cole JT (14 November 2014). "Chapter 2: Metabolism of BCAAs" (PDF). In Rajendram R, Preedy VR, Patel VB (eds.). Branched Chain Amino Acids in Clinical Nutrition. Vol. 1. ISBN   978-1-4939-1923-9.
  5. Lynch CJ, Adams SH (December 2014). "Branched-chain amino acids in metabolic signalling and insulin resistance". Nature Reviews. Endocrinology. 10 (12): 723–36. doi:10.1038/nrendo.2014.171. PMC   4424797 . PMID   25287287.
  6. Xiao F, Yu J, Guo Y, Deng J, Li K, Du Y, et al. (June 2014). "Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice". Metabolism. 63 (6): 841–50. doi:10.1016/j.metabol.2014.03.006. PMID   24684822.
  7. Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, et al. (February 2018). "Restoration of metabolic health by decreased consumption of branched-chain amino acids". The Journal of Physiology. 596 (4): 623–645. doi:10.1113/JP275075. PMC   5813603 . PMID   29266268.
  8. 1 2 3 Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME, Flores V, et al. (May 2021). "The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine". Cell Metabolism. 33 (5): 905–922.e6. doi: 10.1016/j.cmet.2021.03.025 . PMC   8102360 . PMID   33887198.
  9. Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, et al. (July 2016). "Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health". Cell Reports. 16 (2): 520–530. doi:10.1016/j.celrep.2016.05.092. PMC   4947548 . PMID   27346343.
  10. Institute of Medicine (2002). "Protein and Amino Acids". Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. pp. 589–768.
  11. "Effects of Leucine and Isoleucine on Glucose Metabolism". link.springer.com. October 2015. doi:10.1007/978-1-4939-1923-9_6.{{cite web}}: CS1 maint: url-status (link)
  12. "Foods highest in Isoleucine". Self Nutrition Data. Condé Nast. List is in order of highest to lowest of per 200 Calorie serving of the food, not volume or weight.
  13. Marvel, C. S. (1941). "dl-Isoleucine (α-Amino-β-methylvaleric acid)". Organic Syntheses . 21: 60. doi:10.15227/orgsyn.021.0060.; Collective Volume, vol. 3, p. 495
  14. Bouveault L, Locquin R (1905). "Action du sodium sur les éthers des acides monobasiques à fonction simple de la série grasse" [Effect of sodium on the ethers of single-function monobasic acids of the fatty series]. Compt. Rend. (in French). 140: 1593–1595.