Lysine is a base, as are arginine and histidine. The ε-amino group often participates in hydrogen bonding and as a general base in catalysis. (The ε-amino group (NH3+) is attached to the fifth carbon beginning from the α-carbon, which is attached to the carboxyl (C=OOH) group.)
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 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.
β-Aspartate semialdehyde dehydrogenase converts this into β-aspartyl-4-semialdehyde (or β-aspartate-4-semialdehyde). Energy from NADPH is used in this conversion.
This product is reduced to 2,3,4,5-tetrahydrodipicolinate (or Δ1-piperidine-2,6-dicarboxylate, in the figure: (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate) by dihydrodipicolinate reductase. This reaction consumes a NADPH molecule.
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 glutaric 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).
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.
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.
The nutritional requirement per day, in milligrams of lysine per kilogram of body weight, is: infants (3–4 months) 103, children (2 years) 64, older children (10–12 years) 60 to 44, adults 12. For a 70 kg adult, 12 milligrams of lysine per kilogram of body weight is 0.84 grams of lysine. Note that recommendations were subsequently revised upwards, e.g. 30 mg/kg for adults.
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).
Some studies have found that lysine may be beneficial for those with herpes simplex infections. One small randomized, controlled study found that it reduced outbreaks by 2.4 per year.
Lysine has a known anxiolytic action through its effects on serotonin receptors in the intestinal tract. 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, and also led to potentiation of benzodiazepine receptors (common targets of anxiolytic drugs such as Xanax and Ativan). (Note that all of these studies were funded by Ajinomoto, Co. Inc., an industrial manufacturer of lysine.)
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.
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 €1.22 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 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.
^Chen C, Sander JE, Dale NM (2003). "The effect of dietary lysine deficiency on the immune response to Newcastle disease vaccination in chickens". Avian Dis.47 (4): 1346–51. doi:10.1637/7008. PMID14708981.