Leucine

Leucine

Skeletal formula of L-leucine
Names
IUPAC name
Leucine
Other names
2-Amino-4-methylpentanoic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.475 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C6H13NO2/c1-4(2)3-5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t5-/m0/s1 checkY
    Key: ROHFNLRQFUQHCH-YFKPBYRVSA-N checkY
  • InChI=1/C6H13NO2/c1-4(2)3-5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t5-/m0/s1
    Key: ROHFNLRQFUQHCH-YFKPBYRVBU
  • CC(C)C[C@@H](C(=O)O)N
  • Zwitterion: CC(C)C[C@@H](C(=O)[O-])[NH3+]
Properties
C6H13NO2
Molar mass 131.175 g·mol−1
Acidity (pKa) 2.36 (carboxyl), 9.60 (amino)[2]
-84.9·10−6 cm3/mol
Supplementary data page
Leucine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Leucine (symbol Leu or L)[3] 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. Leucine is named after the Greek word for "white": λευκός (leukós, "white"), after its common appearance as a white powder, a property it shares with many other amino acids.[4]

Like valine and isoleucine, leucine is a branched-chain amino acid. The primary metabolic end products of leucine metabolism are acetyl-CoA and acetoacetate; consequently, it is one of the two exclusively ketogenic amino acids, with lysine being the other.[5] It is the most important ketogenic amino acid in humans.[6]

Leucine and β-hydroxy β-methylbutyric acid, a minor leucine metabolite, exhibit pharmacological activity in humans and have been demonstrated to promote protein biosynthesis via the phosphorylation of the mechanistic target of rapamycin (mTOR).[7][8]

  1. ^ a b Binns J, Parsons S, McIntyre GJ (December 2016). "Accurate hydrogen parameters for the amino acid L-leucine" (PDF). Acta Crystallographica Section B. 72 (Pt 6): 885–92. doi:10.1107/S2052520616015699. hdl:20.500.11820/c784fdaf-aa3a-48e4-86a2-d0a0bd7fdb7a. PMID 27910839. S2CID 19288938.
  2. ^ Dawson, R.M.C., et al., Data for Biochemical Research, Oxford, Clarendon Press, 1959.
  3. ^ "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.
  4. ^ Fleck, Michel; Petrosyan, Aram M. (2014). Salts of Amino Acids: Crystallization, Structure and Properties. Cham: Springer International Publishing. doi:10.1007/978-3-319-06299-0. ISBN 978-3-319-06298-3.
  5. ^ Ferrier DR (2013). Biochemistry. Lippincott Williams & Wilkins. ISBN 9781451175622.
  6. ^ Cynober LA (2003). Metabolic & Therapeutic Aspects of Amino Acids in Clinical Nutrition (2nd ed.). CRC Press. p. 101. ISBN 9780203010266.
  7. ^ Silva VR, Belozo FL, Micheletti TO, Conrado M, Stout JR, Pimentel GD, Gonzalez AM (September 2017). "β-hydroxy-β-methylbutyrate free acid supplementation may improve recovery and muscle adaptations after resistance training: a systematic review". Nutrition Research. 45: 1–9. doi:10.1016/j.nutres.2017.07.008. hdl:11449/170023. PMID 29037326. HMB's mechanisms of action are generally considered to relate to its effect on both muscle protein synthesis and muscle protein breakdown (Figure 1) [2, 3]. HMB appears to stimulate muscle protein synthesis through an up-regulation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), a signaling cascade involved in coordination of translation initiation of muscle protein synthesis [2, 4]. Additionally, HMB may have antagonistic effects on the ubiquitin–proteasome pathway, a system that degrades intracellular proteins [5, 6]. Evidence also suggests that HMB promotes myogenic proliferation, differentiation, and cell fusion [7]. ... Exogenous HMB-FA administration has shown to increase intramuscular anabolic signaling, stimulate muscle protein synthesis, and attenuate muscle protein breakdown in humans [2].
  8. ^ Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, et al. (June 2013). "Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism". The Journal of Physiology. 591 (11): 2911–23. doi:10.1113/jphysiol.2013.253203. PMC 3690694. PMID 23551944. The stimulation of MPS through mTORc1-signalling following HMB exposure is in agreement with pre-clinical studies (Eley et al. 2008). ... Furthermore, there was clear divergence in the amplitude of phosphorylation for 4EBP1 (at Thr37/46 and Ser65/Thr70) and p70S6K (Thr389) in response to both Leu and HMB, with the latter showing more pronounced and sustained phosphorylation. ... Nonetheless, as the overall MPS response was similar, this cellular signalling distinction did not translate into statistically distinguishable anabolic effects in our primary outcome measure of MPS. ... Interestingly, although orally supplied HMB produced no increase in plasma insulin, it caused a depression in MPB (−57%). Normally, postprandial decreases in MPB (of ~50%) are attributed to the nitrogen-sparing effects of insulin since clamping insulin at post-absorptive concentrations (5 μU ml−1) while continuously infusing AAs (18 g h−1) did not suppress MPB (Greenhaff et al. 2008), which is why we chose not to measure MPB in the Leu group, due to an anticipated hyperinsulinaemia (Fig. 3C). Thus, HMB reduces MPB in a fashion similar to, but independent of, insulin. These findings are in-line with reports of the anti-catabolic effects of HMB suppressing MPB in pre-clinical models, via attenuating proteasomal-mediated proteolysis in response to LPS (Eley et al. 2008).