Leucine

Leucine ball and stick model spinning

Leucine (symbol Leu or L)<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>Template:Cite book</ref>

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.<ref>Template:Cite book</ref> It is the most important ketogenic amino acid in humans.<ref>Template:Cite book</ref>

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).<ref name="Pimentel 2017 systematic review on HMB">Template:Cite journal</ref><ref name="Pharmacology of HMB-FA in humans in vivo">Template:Cite journal</ref>

Dietary leucineEdit

As a food additive, L-leucine has E number E641 and is classified as a flavor enhancer.<ref>Template:Cite book</ref>

RequirementsEdit

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.<ref name="DRItext">Template:Cite book</ref>

Sources Template:AnchorEdit

Food sources of leucine<ref>Template:Cite book</ref>
Food	g/100g
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 effectsEdit

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.<ref>Template:Cite journal</ref> However, results of comparative studies are conflicted. Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men.<ref>Template:Cite journal</ref> 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 stand-alone, 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.

Both L-leucine and D-leucine protect mice against epileptic seizures.<ref name="pmid26054437">Template:Cite journal</ref> D-leucine also terminates seizures in mice after the onset of seizure activity, at least as effectively as diazepam and without sedative effects.<ref name="pmid26054437"/> Decreased dietary intake of L-leucine lessens adiposity in mice.<ref>Template:Cite journal</ref> High blood levels of leucine are associated with insulin resistance in humans, mice, and rodents.<ref>Template:Cite journal</ref> This might be due to the effect of leucine to stimulate mTOR signaling.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

SafetyEdit

Leucine toxicity, as seen in decompensated maple syrup urine disease, causes delirium and neurologic compromise, and can be life-threatening.<ref>Template:Cite journal</ref>

A high intake of leucine may cause or exacerbate symptoms of pellagra in people with low niacin status because it interferes with the conversion of L-tryptophan to niacin.<ref>Template:Cite journal</ref>

Leucine at a dose exceeding 500 mg/kg/d was observed with hyperammonemia.<ref name="pmid22952178">Template:Cite journal</ref> 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.<ref name="pmid22952178"/><ref name="pmid27138628">Template:Cite journal</ref>

PharmacologyEdit

PharmacodynamicsEdit

Leucine is a dietary amino acid with the capacity to directly stimulate myofibrillar muscle protein synthesis.<ref>Template:Cite journal</ref> This effect of leucine results from its role as an activator of the mechanistic target of rapamycin (mTOR),<ref name="Pharmacology of HMB-FA in humans in vivo" /> a serine-threonine protein kinase that regulates protein biosynthesis and cell growth. The activation of mTOR by leucine is mediated through Rag GTPases,<ref name="pmid28963468">Template:Cite journal</ref><ref name="pmid23361334">Template:Cite journal</ref><ref name="pmid18497260">Template:Cite journal</ref> leucine binding to leucyl-tRNA synthetase,<ref name="pmid28963468" /><ref name="pmid23361334" /> leucine binding to sestrin 2,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> and possibly other mechanisms.

Metabolism in humansEdit

Template:Leucine metabolism in humans

Leucine metabolism occurs in many tissues in the human body; however, most dietary leucine is metabolized within the liver, adipose tissue, and muscle tissue.<ref name="pmid4855772"/> Adipose and muscle tissue use leucine in the formation of sterols and other compounds.<ref name="pmid4855772"/> Combined leucine use in these two tissues is seven times greater than in the liver.<ref name="pmid4855772">Template:Cite journal</ref>

Template:Trim

A small fraction of Template:Nowrap metabolism – less than 5% in all tissues except the testes, where it accounts for about 33% – is initially catalyzed by leucine aminomutase, producing β-leucine, which is subsequently metabolized into Template:Nowrap (β-KIC), β-ketoisocaproyl-CoA, and then acetyl-CoA by a series of uncharacterized enzymes.<ref name="Leucine metabolism" /><ref name="BRENDA leucine metabolism" />

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Synthesis in nonhuman organismsEdit

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:<ref>Template:Cite book</ref>

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

ChemistryEdit

File:Betain-Leucin.png

(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 not linear.

Racemic leucine had beenTemplate:When 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.<ref>Meierhenrich: Amino acids and the asymmetry of life, Springer-Verlag, 2008, Template:ISBN.</ref>