Leucine
Skeletal formula of L-leucine
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Names | |||
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IUPAC name
Leucine
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Other names
2-Amino-4-methylpentanoic acid
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Identifiers | |||
3D model (
JSmol ) |
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ChEBI | |||
ChEMBL | |||
ChemSpider | |||
DrugBank | |||
ECHA InfoCard
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100.000.475 | ||
IUPHAR/BPS |
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KEGG | |||
PubChem CID
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UNII | |||
CompTox Dashboard (EPA)
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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).
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Leucine (symbol Leu or L)
Like
Leucine and
Dietary leucine
As a
Requirements
The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for essential amino acids in 2002. For leucine, for adults 19 years and older, 42 mg/kg body weight/day.[10]
Sources
Food | g/100g |
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Whey protein concentrate, dry powder | 10.0-12.0 |
Soy protein concentrate, dry powder | 7.5-8.5 |
Pea protein concentrate, dry powder | 6.6 |
Soybeans , mature seeds, roasted, salted |
2.87 |
Hemp seed, hulled | 2.16 |
Beef, round, top round, raw | 1.76 |
Peanuts | 1.67 |
Fish, salmon, pink, raw | 1.62 |
Wheat germ |
1.57 |
Almonds |
1.49 |
Chicken, broilers or fryers, thigh, raw | 1.48 |
Chicken egg , yolk, raw |
1.40 |
Oats | 1.28 |
Edamame (soybeans, green, raw) | 0.93 |
Beans, pinto, cooked | 0.78 |
Lentils , cooked |
0.65 |
Chickpea, cooked | 0.63 |
Corn, yellow | 0.35 |
Cow milk , whole, 3.25% milk fat |
0.27 |
Rice, brown, medium-grain, cooked | 0.19 |
Milk, human, mature, fluid | 0.10 |
Health effects
As a
Both L-leucine and D-leucine protect mice against epileptic seizures.[14] D-leucine also terminates seizures in mice after the onset of seizure activity, at least as effectively as diazepam and without sedative effects.[14] Decreased dietary intake of L-leucine lessens adiposity in mice.[15] High blood levels of leucine are associated with insulin resistance in humans, mice, and rodents.[16] This might be due to the effect of leucine to stimulate mTOR signaling.[17] Dietary restriction of leucine and the other BCAAs can reverse diet-induced obesity in wild-type mice by increasing energy expenditure, and can restrict fat mass gain of hyperphagic rats.[18][19]
Safety
Leucine toxicity, as seen in decompensated maple syrup urine disease, causes delirium and neurologic compromise, and can be life-threatening.[20]
A high intake of leucine may cause or exacerbate symptoms of
Leucine at a dose exceeding 500 mg/kg/d was observed with hyperammonemia.[22] As such, unofficially, a tolerable upper intake level (UL) for leucine in healthy adult men can be suggested at 500 mg/kg/d or 35 g/d under acute dietary conditions.[22][23]
Pharmacology
Pharmacodynamics
Leucine is a
and possibly other mechanisms.Metabolism in humans
Leucine metabolism in humans
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Leucine metabolism occurs in many
In healthy individuals, approximately 60% of dietary L-leucine is metabolized after several hours, with roughly 5% (2–10% range) of dietary L-leucine being converted to
The vast majority of L-leucine metabolism is initially catalyzed by the
A small fraction of L-leucine metabolism – less than 5% in all tissues except the
The metabolism of HMB is catalyzed by an uncharacterized enzyme which converts it to
Synthesis in non-human organisms
Leucine is an essential amino acid in the diet of animals because they lack the complete enzyme pathway to synthesize it de novo from potential precursor compounds. Consequently, they must ingest it, usually as a component of proteins. Plants and microorganisms synthesize leucine from pyruvic acid with a series of enzymes:[42]
- Acetolactate synthase
- Acetohydroxy acid isomeroreductase
- Dihydroxyacid dehydratase
- α-Isopropylmalate synthase
- α-Isopropylmalate isomerase
- Leucine aminotransferase
Synthesis of the small, hydrophobic amino acid valine also includes the initial part of this pathway.
Chemistry
Leucine is a branched-chain amino acid (BCAA) since it possesses an
See also
- Leucines, the isomers and derivatives of leucine
- Leucine zipper, a common motif in transcription factor proteins
Notes
- ^ This reaction is catalyzed by an unknown thioesterase enzyme.[31][32]
References
- ^ S2CID 19288938.
- ^ Dawson, R.M.C., et al., Data for Biochemical Research, Oxford, Clarendon Press, 1959.
- ^ "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.
- ISBN 978-3-319-06298-3.
- ISBN 9781451175622.
- ISBN 9780203010266.
- 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].
- ^ 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).
- ISBN 978-0307408921.
- ISBN 978-0-309-08525-0.
- ^ National Nutrient Database for Standard Reference. U.S. Department of Agriculture. Archived from the original on 3 March 2015. Retrieved 16 September 2009.
- PMID 16195315.
- PMID 19321567.
- ^ PMID 26054437.
- PMID 27346343.
- PMID 25287287.
- PMID 26185979.
- PMID 29266268.
- PMID 27408778.
- PMID 15930465.
- PMID 25520560.
- ^ PMID 22952178.
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.
- S2CID 3708265.
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
- PMID 15051860.
- ^ PMID 28963468.
- ^ PMID 23361334.
- PMID 18497260.
- PMID 26449471.
- PMID 26586190.
- PMID 25263562.
- ^ a b c "KEGG Reaction: R10759". Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. Archived from the original on 1 July 2016. Retrieved 24 June 2016.
- ^ PMID 21918059.
Reduced activity of MCC impairs catalysis of an essential step in the mitochondrial catabolism of the BCAA leucine. Metabolic impairment diverts methylcrotonyl CoA to 3-hydroxyisovaleryl CoA in a reaction catalyzed by enoyl-CoA hydratase (22, 23). 3-Hydroxyisovaleryl CoA accumulation can inhibit cellular respiration either directly or via effects on the ratios of acyl CoA:free CoA if further metabolism and detoxification of 3-hydroxyisovaleryl CoA does not occur (22). The transfer to carnitine by 4 carnitine acyl-CoA transferases distributed in subcellular compartments likely serves as an important reservoir for acyl moieties (39–41). 3-Hydroxyisovaleryl CoA is likely detoxified by carnitine acetyltransferase producing 3HIA-carnitine, which is transported across the inner mitochondrial membrane (and hence effectively out of the mitochondria) via carnitine-acylcarnitine translocase (39). 3HIA-carnitine is thought to be either directly deacylated by a hydrolase to 3HIA or to undergo a second CoA exchange to again form 3-hydroxyisovaleryl CoA followed by release of 3HIA and free CoA by a thioesterase.
- ^ PMID 23374455.
- ^ ISBN 978-0-12-387784-0. Archived from the original on 22 March 2018. Retrieved 6 June 2016.
Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours ... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds
Figure 8.57: Metabolism of L-leucine Archived 22 March 2018 at the Wayback Machine - ^ PMID 4855772.
- S2CID 29717535.
In conclusion, HMB treatment clearly appears to be a safe potent strategy against sarcopenia, and more generally against muscle wasting, because HMB improves muscle mass, muscle strength, and physical performance. It seems that HMB is able to act on three of the four major mechanisms involved in muscle deconditioning (protein turnover, apoptosis, and the regenerative process), whereas it is hypothesized to strongly affect the fourth (mitochondrial dynamics and functions). Moreover, HMB is inexpensive (~30– 50 US dollars per month at 3 g per day) and may prevent osteopenia (Bruckbauer and Zemel, 2013; Tatara, 2009; Tatara et al., 2007, 2008, 2012) and decrease cardiovascular risks (Nissen et al., 2000). For all these reasons, HMB should be routinely used in muscle-wasting conditions especially in aged people. ... 3 g of CaHMB taken three times a day (1 g each time) is the optimal posology, which allows for continual bioavailability of HMB in the body (Wilson et al., 2013)
- ^ "KEGG Reaction: R04137". Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. Archived from the original on 1 July 2016. Retrieved 24 June 2016.
- ^ "Homo sapiens: 4-hydroxyphenylpyruvate dioxygenase reaction". MetaCyc. SRI International. 20 August 2012. Retrieved 6 June 2016.
- ^ a b "Leucine metabolism". BRENDA. Technische Universität Braunschweig. Archived from the original on 17 August 2016. Retrieved 12 August 2016.
- ISBN 978-1-57259-153-0.
- ISBN 978-3-540-76885-2.
External links
- Leucine Biosynthesis at the Wayback Machine (archived 2017-05-06)