Lysine (abbreviated as Lys or K), encoded by the codons AAA and AAG, is an ?-amino acid that is used in the biosynthesis of proteins. It contains an ?-amino group (which is in the protonated -NH3+ form under biological conditions), an ?-carboxylic acid group (which is in the deprotonated -COO- form under biological conditions), and a side chain lysyl ((CH2)4NH2), classifying it as a charged (at physiological pH), aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it and thus it must be obtained from the diet.
Lysine is a base, as are arginine and histidine. The ?-amino group often participates in hydrogen bonding and as a general base in catalysis. The ?-amino group (NH3+) is attached to the fifth carbon from the ?-carbon, which is attached to the carboxyl (C=OOH) group.
Common posttranslational modifications include methylation of the ?-amino group, giving methyl-, dimethyl-, and trimethyllysine (the latter occurring in calmodulin); also acetylation, sumoylation, ubiquitination, and hydroxylation - producing the hydroxylysine in collagen and other proteins. O-Glycosylation of hydroxylysine residues in the endoplasmic reticulum or Golgi apparatus is used to mark certain proteins for secretion from the cell. In opsins like rhodopsin and the visual opsins (encoded by the genes OPN1SW, OPN1MW, and OPN1LW), retinaldehyde forms a Schiff base with a conserved lysine residue, and interaction of light with the retinylidene group causes signal transduction in color vision (See visual cycle for details). Deficiencies may cause blindness, as well as many other problems due to its ubiquitous presence in proteins.
Maps, Directions, and Place Reviews
Biosynthesis
As an essential amino acid, lysine is not synthesized in animals, hence it must be ingested as lysine or lysine-containing proteins. In plants and most bacteria, it is synthesized from aspartic acid (aspartate):
- L-aspartate is first converted to L-aspartyl-4-phosphate by aspartokinase (or Aspartate kinase). ATP is needed as an energy source for this step.
- ?-Aspartate semialdehyde dehydrogenase converts this into ?-aspartyl-4-semialdehyde (or ?-aspartate-4-semialdehyde). Energy from NADPH is used in this conversion.
- 4-hydroxy-tetrahydrodipicolinate synthase adds a pyruvate group to the ?-aspartyl-4-semialdehyde, and a water molecule is removed. This causes cyclization and gives rise to (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate.
- This product is reduced to 2,3,4,5-tetrahydrodipicolinate (or ?1-piperidine-2,6-dicarboxylate, in the figure: (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate) by 4-hydroxy-tetrahydrodipicolinate reductase. This reaction consumes an NADPH molecule and releases a second water molecule.
- Tetrahydrodipicolinate N-acetyltransferase opens this ring and gives rise to N-succinyl-L-2-amino-6-oxoheptanedionate (or N-acyl-2-amino-6-oxopimelate). Two water molecules and one acyl-CoA (succinyl-CoA) enzyme are used in this reaction.
- N-succinyl-L-2-amino-6-oxoheptanedionate is converted into N-succinyl-LL-2,6-diaminoheptanedionate (N-acyl-2,6-diaminopimelate). This reaction is catalyzed by the enzyme succinyl diaminopimelate aminotransferase. A glutamic acid molecule is used in this reaction and an oxoacid is produced as a byproduct.
- N-succinyl-LL-2,6-diaminoheptanedionate (N-acyl-2,6-diaminopimelate)is converted into LL-2,6-diaminoheptanedionate (L,L-2,6-diaminopimelate) by succinyl diaminopimelate desuccinylase (acyldiaminopimelate deacylase). A water molecule is consumed in this reaction and a succinate is produced a byproduct.
- LL-2,6-diaminoheptanedionate is converted by diaminopimelate epimerase into meso-2,6-diamino-heptanedionate (meso-2,6-diaminopimelate).
- Finally, meso-2,6-diamino-heptanedionate is converted into L-lysine by diaminopimelate decarboxylase.
Enzymes involved in this biosynthesis include:
- Aspartokinase
- Aspartate-semialdehyde dehydrogenase
- 4-hydroxy-tetrahydrodipicolinate synthase
- 4-hydroxy-tetrahydrodipicolinate reductase
- 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase
- Succinyldiaminopimelate transaminase
- Succinyl-diaminopimelate desuccinylase
- Diaminopimelate epimerase
- Diaminopimelate decarboxylase.
It is worth noting, however, that in fungi, euglenoids and some prokaryotes lysine is synthesized via the alpha-aminoadipate pathway.
Llysine Benefits For Cats Video
Metabolism
Lysine is metabolised in mammals to give acetyl-CoA, via an initial transamination with ?-ketoglutarate. The bacterial degradation of lysine yields cadaverine by decarboxylation.
Allysine is a derivative of lysine, used in the production of elastin and collagen. It is produced by the actions of the enzyme lysyl oxidase on lysine in the extracellular matrix and is essential in the crosslink formation that stabilizes collagen and elastin.
Synthesis
Synthetic, racemic lysine has long been known. A practical synthesis starts from caprolactam. Industrially, L-lysine is usually manufactured by a fermentation process using Corynebacterium glutamicum; production exceeds 600,000 tons a year.
L-lysine HCl is used as a dietary supplement, providing 80.03% L-lysine. As such, 1 g of L-lysine is contained in 1.25 g of L-lysine HCl.
Dietary sources
The nutritional requirement per day, in milligrams of lysine per kilogram of body weight, is: infants (3-4 months) 103 mg/kg, children (2 years) 64 mg/kg, older children (10-12 years) 44 to 60 mg/kg, adults 12 mg/kg. For a 70 kg adult, 12 milligrams of lysine per kilogram of body weight is 0.84 grams of lysine. Recommendations for adults have been revised upwards to 30 mg/kg.
Good sources of lysine are high-protein foods such as eggs, meat (specifically red meat, lamb, pork, and poultry), soy, beans and peas, cheese (particularly Parmesan), and certain fish (such as cod and sardines).
Lysine is the limiting amino acid (the essential amino acid found in the smallest quantity in the particular foodstuff) in most cereal grains, but is plentiful in most pulses (legumes). Consequently, meals that combine cereal grains and legumes, such as the Indian dal with rice, Middle Eastern hummus, ful medames, falafel with pita bread, the Mexican beans with rice or tortilla have arisen to provide complete protein in diets that are, by choice or by necessity, vegetarian. A food is considered to have sufficient lysine if it has at least 51 mg of lysine per gram of protein (so that the protein is 5.1% lysine).
Foods containing significant proportions of lysine include:
Properties
L-Lysine plays a major role in calcium absorption; building muscle protein; recovering from surgery or sports injuries; and the body's production of hormones, enzymes, and antibodies.
Modifications
Lysine can be modified through acetylation (acetyllysine), methylation (methyllysine), ubiquitination, sumoylation, neddylation, biotinylation, pupylation, and carboxylation, which tends to modify the function of the protein of which the modified lysine residue(s) are a part.
Clinical significance
A systematic Cochrane Review (investigating all clinical trials, in vitro studies and mechanism of action) published in 2015 showed there is no evidence that lysine supplementation is effective against herpes simplex virus and it has not been approved by the FDA for herpes simplex suppression.
Some studies have shown that lysine supplementation can decrease cold sore outbreaks and reduce healing time. Diets high in Arginine feed the herpes simplex virus and increase replication rate, while diets high in lysine can decrease replication rate
Lysine has anxiolytic action through its effects on serotonin receptors in the intestinal tract, and is also hypothesized to reduce anxiety through serotonin regulation in the amygdala. One study on rats showed that overstimulation of the 5-HT4 receptors in the gut are associated with anxiety-induced intestinal pathology. Lysine, acting as a serotonin antagonist and therefore reducing the overactivity of these receptors, reduced signs of anxiety and anxiety-induced diarrhea in the sample population. Another study showed that lysine deficiency leads to a pathological increase in serotonin in the amygdala, a brain structure that is involved in emotional regulation and the stress response. Human studies have also shown correlations between reduced lysine intake and anxiety. A population-based study in Syria included 93 families whose diet is primarily grain-based and therefore likely to be deficient in lysine. Fortification of grains with lysine was shown to reduce markers of anxiety, including cortisol levels; Smiriga and colleagues hypothesized that anxiety reduction from lysine occurs through mechanism of serotonin alterations in the central amygdala; older primary research reports hypothesized lysine to reduce anxiety through the potentiation of benzodiazepine receptors (common targets of anxiolytic drugs such as Xanax and Ativan).
There are lysine conjugates that show promise in the treatment of cancer, by causing cancerous cells to destroy themselves when the drug is combined with the use of phototherapy, while leaving non-cancerous cells unharmed.
Lysine deficiency causes immunodeficiency in chickens. One cause of relative lysine deficiency is cystinuria, where there is impaired hepatic resorption of basic, or positively charged amino acids, including lysine. The accompanying urinary cysteine results because the same deficient amino acid transporter is normally present in the kidney as well.
Limited studies suggest that a high-lysine diet or L-lysine monochloride supplements may have a moderating effect on blood pressure and the incidence of stroke.
The stimulant pro-drug lisdexamfetamine (Vyvanse) consists of lysine attached to the amine of d-amphetamine and is enzymatically cleaved off to produce the active drug, d-amphetamine.
Use of lysine in animal feed
Lysine production for animal feed is a major global industry, reaching in 2009 almost 700,000 tonnes for a market value of over EUR1.22 billion. Lysine is an important additive to animal feed because it is a limiting amino acid when optimizing the growth of certain animals such as pigs and chickens for the production of meat. Lysine supplementation allows for the use of lower-cost plant protein (maize, for instance, rather than soy) while maintaining high growth rates, and limiting the pollution from nitrogen excretion. In turn, however, phosphate pollution is a major environmental cost when corn is used as feed for poultry and swine.
Lysine is industrially produced by microbial fermentation, from a base mainly of sugar. Genetic engineering research is actively pursuing bacterial strains to improve the efficiency of production and allow lysine to be made from other substrates.
In popular culture
The 1993 film Jurassic Park (based on the 1990 Michael Crichton novel of the same name) features dinosaurs that were genetically altered so that they could not produce lysine. This was known as the "lysine contingency" and was supposed to prevent the cloned dinosaurs from surviving outside the park, forcing them to be dependent on lysine supplements provided by the park's veterinary staff. In reality, no animals are capable of producing lysine (it is an essential amino acid).
Lysine is the favorite amino acid of the character Sheldon Cooper in the television show, The Big Bang Theory. It was mentioned in season 2, episode 13, "The Friendship Algorithm".
In 1996, lysine became the focus of a price-fixing case, the largest in United States history. The Archer Daniels Midland Company paid a fine of US$100 million, and three of its executives were convicted and served prison time. Also found guilty in the price-fixing case were two Japanese firms (Ajinomoto, Kyowa Hakko) and a South Korean firm (Sewon). Secret video recordings of the conspirators fixing lysine's price can be found online or by requesting the video from the U.S. Department of Justice, Antitrust Division. This case served as the basis of the movie The Informant!, and a book of the same title.
Source of the article : Wikipedia
EmoticonEmoticon