Leucine

Leucine

L-Leucine

L-Leucine at physiological pH
Names
IUPAC name
Leucine
Other names
2-Amino-4-methylpentanoic acid
Identifiers
61-90-5 YesY
ChEBI CHEBI:57427 YesY
ChEMBL ChEMBL291962 N
ChemSpider 5880 YesY
DrugBank DB01746 YesY
3312
Jmol 3D model Interactive image
KEGG D00030 YesY
PubChem 6106
UNII GMW67QNF9C YesY
Properties
C6H13NO2
Molar mass 131.18 g·mol−1
Acidity (pKa) 2.36 (carboxyl), 9.60 (amino)[1]
Supplementary data page
Refractive index (n),
Dielectric constant (εr), etc.
Thermodynamic
data
 Phase behaviour
solid–liquid–gas
UV, IR, NMR, MS
N verify (what is YesYN ?)
Infobox references

Leucine (abbreviated as Leu or L; encoded by the six codons UUA, UUG, CUU, CUC, CUA, and CUG) is an α-amino acid 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 an isobutyl side chain, classifying it as a nonpolar (at physiological pH) amino acid. It is essential in humans—meaning the body cannot synthesize it and thus must obtain from the diet.

Leucine is a major component of the subunits in ferritin, astacin, and other "buffer" proteins.

Biology

Leucine is used in the liver, adipose tissue, and muscle tissue. Adipose and muscle tissue use leucine in the formation of sterols. Combined leucine use in these two tissues is seven times greater than in the liver.[2]

Biosynthesis in plants

As it is an essential amino acid, animals cannot synthesize leucine. Consequently, they must ingest it, usually as a component of proteins. Plants and microorganisms synthesize leucine from pyruvic acid with a series of enzymes:[3]

Synthesis of the small, hydrophobic amino acid valine also includes the initial part of this pathway.

Metabolism in humans

Human metabolic pathway for β-hydroxy β-methylbutyric acid (HMB) and isovaleryl-CoA, relative to leucine.[4] Like leucine, HMB also activates mTOR signaling, in addition to other anabolic and anti-catabolic signaling mechanisms (e.g., proteasome inhibition) in skeletal muscle tissue.[4][5] Of the two major pathways, leucine is mostly metabolized into isovaleryl-CoA, while only 5% or so is metabolized into HMB.[4]

Effects

Leucine is an mTOR activator. It is a dietary amino acid with the capacity to directly stimulate muscle protein synthesis.[6] As a dietary supplement, leucine has been found to slow the degradation of muscle tissue by increasing the synthesis of muscle proteins in aged rats.[7] However, results of comparative studies are conflicted. Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men.[8] More studies are needed, preferably ones based on an objective, random sample of society. Factors such as lifestyle choices, age, gender, diet, exercise, etc. must be factored into the analyses to isolate the effects of supplemental leucine as a standalone, or if taken with other branched chain amino acids (BCAAs). Until then, dietary supplemental leucine cannot be associated as the prime reason for muscular growth or optimal maintenance for the entire population.

Leucine potently activates the mammalian target of rapamycin kinase that regulates cell growth. Infusion of leucine into the rat brain has been shown to decrease food intake and body weight via activation of the mTOR pathway.[9]

Both L-leucine and D-leucine protect mice against seizures.[10] D-leucine also terminates seizures in mice after the onset of seizure activity, at least as effectively as diazepam and without sedative effects.[10]

Safety

Leucine toxicity, as seen in decompensated maple syrup urine disease (MSUD), causes delirium and neurologic compromise, and can be life-threatening.

Excess leucine may be a cause of pellagra, whose main symptoms are "the four D's": diarrhea, dermatitis, dementia and death,[11] though the relationship is unclear.[12]

Leucine at a dose exceeding 500 mg/kg/d was observed with hyperammonemia.[13] As such, the UL for leucine in healthy adult men can be suggested at 500 mg/kg/d or 35 g/d under acute dietary conditions.[13][14]

Dietary sources

Food sources of leucine[15]
Food g/100g
Soybeans, mature seeds, raw 2.97
Beef, round, top round, separable lean and fat, trimmed to 3 mm (1⁄8 in) fat, select, raw 1.76
Hemp seeds, whole seeds, raw 1.7
Peanuts 1.672
Salami, pork 1.63
Fish, salmon, pink, raw 1.62
Wheat germ 1.571
Almonds 1.488
Chicken, broilers or fryers, thigh, meat only, raw 1.48
Chicken egg, yolk, raw, fresh 1.40
Oat 1.284
Hemp hearts, shelled hemp seeds, raw 1.1
Beans, pinto, cooked 0.765
Lentils, cooked 0.654
Chickpea, cooked 0.631
Corn, yellow 0.348
Cow milk, whole, 3.25% milk fat 0.27
Rice, brown, medium-grain, cooked 0.191
Milk, human, mature, fluid 0.10

Chemical properties

(S)-Leucine (or L-leucine), left; (R)-leucine (or D-leucine), right, in zwitterionic form at neutral pH

Leucine is a branched-chain amino acid (BCAA) since it possesses an aliphatic side-chain that is non-linear.

Racemic leucine had been subjected to circularly polarized synchrotron radiation to better understand the origin of biomolecular asymmetry. An enantiomeric enhancement of 2.6% had been induced, indicating a possible photochemical origin of biomolecules' homochirality.[16]

Other uses

As a food additive, L-leucine has E number E641 and is classified as a flavor enhancer.[17]

See also

References

  1. ↑ Dawson, R.M.C., et al., Data for Biochemical Research, Oxford, Clarendon Press, 1959.
  2. ↑ J. Rosenthal, et al. Department of Medicine, University of Toronto, Toronto, Canada. "Metabolic fate of leucine: A significant sterol precursor in adipose tissue and muscle". American Journal of Physiology Vol. 226, No. 2, p. 411-418. Retrieved 2008-03-25.
  3. ↑ Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6.
  4. 1 2 3 Wilson JM, Fitschen PJ, Campbell B, Wilson GJ, Zanchi N, Taylor L, Wilborn C, Kalman DS, Stout JR, Hoffman JR, Ziegenfuss TN, Lopez HL, Kreider RB, Smith-Ryan AE, Antonio J (February 2013). "International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)". J. Int. Soc. Sports. Nutr. 10 (1): 6. doi:10.1186/1550-2783-10-6. PMC 3568064. PMID 23374455. The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations. ... Indeed, HMB has been shown to decrease proteasome expression [72] and activity [72,78-80] during catabolic states, thus attenuating skeletal muscle protein degradation through the ubiquitin-proteasome pathway.
  5. ↑ Portal S, Eliakim A, Nemet D, Halevy O, Zadik Z (July 2010). "Effect of HMB supplementation on body composition, fitness, hormonal profile and muscle damage indices". J. Pediatr. Endocrinol. Metab. 23 (7): 641–50. PMID 20857835. There is a huge market for ergogenic supplements for athletes. However, only a few products have been proven to have ergogenic effects and to be effective at improving muscle strength and body composition. One such supplement is beta-hydroxy beta-methylbutyrate (HMB). ... Several studies have shown that combining exercise training with HMB supplementation leads to increased muscle mass and strength, and there is some anecdotal evidence of aerobic improvement. However, HMB supplementation has been found to be effective mainly for untrained individuals. While previous reviews have emphasized three main pathways for HMB's mode of action: 1) enhancement of sarcolemmal integrity via cytosolic cholesterol, 2) inhibition of protein degradation via proteasomes, and 3) increased protein synthesis via the mTOR pathway, more recent studies have suggested additional possible mechanisms for its physiological effects. These include decreased cell apoptosis and enhanced cell survival, increased proliferation, differentiation and fusion via the MAPK/ERK and PI3K/Akt pathways, and enhanced IGF-I transcription.
  6. ↑ Etzel MR (2004). "Manufacture and use of dairy protein fractions". The Journal of Nutrition 134 (4): 996S–1002S. PMID 15051860.
  7. ↑ L. Combaret, et al. Human Nutrition Research Centre of Clermont-Ferrand. "A leucine-supplemented diet restores the defective postprandial inhibition of proteasome-dependent proteolysis in aged rat skeletal muscle". Journal of Physiology Volume 569, issue 2, p. 489-499. Retrieved 2008-03-25.
  8. ↑ Verhoeven, Suzanne; Vanschoonbeek, Kristof; Verdijk, Lex B.; Koopman, René; Wodzig, Will K.W.H.; Dendale, Paul; van Loon, Luc JC (May 2009). "Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men". Am J Clin Nutr 89 (5): 1468–75. doi:10.3945/ajcn.2008.26668. PMID 19321567.
  9. ↑ Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ (2006). "Hypothalamic mTOR signaling regulates food intake". Science 312 (5775): 927–930. doi:10.1126/science.1124147. PMID 16690869.
  10. 1 2 Hartman AL, Santos P, O'Riordan KJ, Stafstrom CE, Marie Hardwick J (2015). "Potent anti-seizure effects of D-leucine". Neurobiology of Disease 82: 46–53. doi:10.1016/j.nbd.2015.05.013. PMID 26054437. Retrieved 2015-11-26.
  11. ↑ Hegyi J, Schwartz R, Hegyi V (2004). "Pellagra: dermatitis, dementia, and diarrhea". Int J Dermatol 43 (1): 1–5. doi:10.1111/j.1365-4632.2004.01959.x. PMID 14693013.
  12. ↑ Bapurao S, Krishnaswamy K (1978). "Vitamin B6 nutritional status of pellagrins and their leucine tolerance". Am J Clin Nutr 31 (5): 819–24. PMID 206127.
  13. 1 2 Elango R, Chapman K, Rafii M, Ball RO, Pencharz PB (2012). "Determination of the tolerable upper intake level of leucine in acute dietary studies in young men". The American Journal of Clinical Nutrition 96 (4): 759–67. doi:10.3945/ajcn.111.024471. PMID 22952178. Retrieved 2015-12-07. A significant increase in blood ammonia concentrations above normal values, plasma leucine concentrations, and urinary leucine excretion were observed with leucine intakes >500 mg · kg⁻¹ · d⁻¹. The oxidation of l-[1-¹³C]-leucine expressed as label tracer oxidation in breath (F¹³CO₂), leucine oxidation, and α-ketoisocaproic acid (KIC) oxidation led to different results: a plateau in F¹³CO₂ observed after 500 mg · kg⁻¹ · d⁻¹, no clear plateau observed in leucine oxidation, and KIC oxidation appearing to plateau after 750 mg · kg⁻¹ · d⁻¹. On the basis of plasma and urinary variables, the UL for leucine in healthy adult men can be suggested at 500 mg · kg⁻¹ · d⁻¹ or ~35 g/d as a cautious estimate under acute dietary conditions.
  14. ↑ Rasmussen B, Gilbert E, Turki A, Madden K, Elango R (2016). "Determination of the safety of leucine supplementation in healthy elderly men". Amino Acids. doi:10.1007/s00726-016-2241-0. PMID 27138628. Retrieved 2016-05-06. the upper limit for leucine intake in healthy elderly could be set similar to young men at 500 mg kg-1 day-1 or ~35 g/day for an individual weighing 70 kg
  15. ↑ National Nutrient Database for Standard Reference. U.S. Department of Agriculture. Retrieved 2009-09-16.
  16. ↑ Meierhenrich: Amino acids and the asymmetry of life, Springer-Verlag, 2008, ISBN 978-3-540-76885-2.
  17. ↑ Winter, Ruth (2009). A consumer's dictionary of food additives (7th ed.). New York: Three Rivers Press. ISBN 0307408922.

External links

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