Lysine is an α-amino acid, used in the biosynthesis of proteins. It contains an α-amino group, an α-carboxylic acid group, a side chain lysyl, classifying it as a basic, aliphatic amino acid, it is encoded by the codons, AAA and AAG. Like all other amino acids, the α-carbon is chiral and lysine may refer to either enantiomer or a racemic mixture of both. For the purpose of this article, lysine will refer to the biologically active enantiomer L-lysine, where the α-carbon is in the S configuration; the human body cannot synthesize lysine. It must be obtained from the diet. In organisms that synthesise lysine, it has two main biosynthetic pathways, the diaminopimelate and α-aminoadipate pathways, which employ different enzymes and substrates and are found in different organisms. Lysine catabolism occurs through one of several pathways, the most common of, the saccharopine pathway. Lysine plays several roles in humans, most proteinogenesis, but in the crosslinking of collagen polypeptides, uptake of essential mineral nutrients, in the production of carnitine, key in fatty acid metabolism.
Lysine is often involved in histone modifications, thus, impacts the epigenome. The ε-amino group participates in hydrogen bonding and as a general base in catalysis; the ε-ammonium group is attached to the fourth carbon from the α-carbon, attached to the carboxyl group. Due to its importance in several biological processes, a lack of lysine can lead to several disease states including defective connective tissues, impaired fatty acid metabolism and systemic protein-energy deficiency. In contrast, an overabundance of lysine, caused by ineffective catabolism, can cause severe neurological disorders. Lysine was first isolated by the German biological chemist Ferdinand Heinrich Edmund Drechsel in 1889 from the protein casein in milk, he named it "lysin". In 1902, the German chemists Emil Fischer and Fritz Weigert determined lysine's chemical structure by synthesizing it. Two different pathways have been identified in nature for the synthesis of lysine; the diaminopimelate pathway belongs to the aspartate derived biosynthetic family, involved in the synthesis of threonine and isoleucine.
Whereas the α-aminoadipate pathway is part of the glutamate biosynthetic family. The DAP pathway is found in both prokaryotes and plants and begins with the dihydrodipicolinate synthase catalysed condensation reaction between the aspartate derived, L-aspartate semialdehyde, pyruvate to form -4-hydroxy-2,3,4,5-tetrahydro--dipicolinic acid; the product is reduced by dihydrodipicolinate reductase, with NADH as a proton donor, to yield 2,3,4,5-tetrahydrodipicolinate. From this point on, there are four pathway variations found in different species, namely the acetylase, aminotransferase and succinylase pathways. Both the acetylase and succinylase variant pathways use four enzyme catalysed steps, the aminotransferase pathway uses two enzymes, the dehydrogenase pathway uses a single enzyme; these four variant pathways converge at the formation of the penultimate product, meso‑diaminopimelate, subsequently enzymatically decarboxylated in an irreversible reaction catalysed by diaminopimelate decarboxylase to produce L-lysine.
The DAP pathway is regulated at multiple levels, including upstream at the enzymes involved in aspartate processing as well as at the initial DHDPS catalysed condensation step. Lysine imparts a strong negative feedback loop on these enzymes and, regulates the entire pathway; the AAA pathway involves the condensation of α-ketoglutarate and acetyl-CoA via the intermediate AAA for the synthesis of L-lysine. This pathway has been shown to be present in several yeast species, as well as protists and higher fungi, it has been reported that an alternative variant of the AAA route has been found in Thermus thermophilus and Pyrococcus horikoshii, which could indicate that this pathway is more spread in prokaryotes than proposed. The first and rate-limiting step in the AAA pathway is the condensation reaction between acetyl-CoA and α‑ketoglutarate catalysed by homocitrate-synthase to give the intermediate homocitryl‑CoA, hydrolysed by the same enzyme to produce homocitrate. Homocitrate is enzymatically dehydrated by homoaconitase to yield cis-homoaconitate.
HAc catalyses a second reaction in which cis-homoaconitate undergoes rehydration to produce homoisocitrate. The resulting product undergoes an oxidative decarboxylation by homoisocitrate dehydrogenase to yield α‑ketoadipate. AAA is formed via a pyridoxal 5′-phosphate -dependent aminotransferase, using glutamate as the amino donor. From this point on, the AAA pathway differs depending on the kingdom. In fungi, AAA is reduced to α‑aminoadipate-semialdehyde via AAA reductase in a unique process involving both adenylation and reduction, activated by a phosphopantetheinyl transferase. Once the semialdehyde is formed, saccharopine reductase catalyses a condensation reaction with glutamate and NADH, as a proton donor, the imine is reduced to produce the penultimate product, saccharopine; the final step of the pathway in fungi involves the saccharopine dehydrogenase catalysed oxidative deamination of saccharopine, resulting in L-lysine. In a variant AAA pathway found
Giovanni Lodetti is an Italian former professional footballer who played as a midfielder. A hard-working player, he supported his more creative teammates defensively, excelling as a defensive midfielder due to his stamina and his ability to read the game. Despite his supporting role in midfield, he possessed good technique and creativity, as well as an eye for goal, which saw him participate in his teams attacking moves. Lodetti is remembered for his time as a defensive midfielder with Italian club Milan, with which he achieved great domestic and international success in the 60s alongside playmaker Gianni Rivera, winning two Serie A titles, a Coppa Italia, two European Cups, a Cup Winners' Cup, an Intercontinental Cup, he also played for Sampdoria and Novara, before retiring in 1978. Lodetti represented the Italian national side at the 1966 World Cup in England, where they were eliminated in the first round, he was a member of the national squad in Italy's victorious UEFA Euro 1968 campaign on home soil.
Although he was set to participate in the 1970 World Cup, in which Italy reached the final, he was dropped last minute due to an injury to Anastasi, which led manager Ferruccio Valcareggi to call up Roberto Boninsegna and Pierino Prati in his place. In total he represented his national team 17 times between 1968, scoring two goals, he represented the under-21 side in their victorious campaign at the 1963 Mediterranean games. A. C. Milan Serie A: 1961–62, 1967–68 Coppa Italia: 1966–67 European Cup: 1962–63, 1968–69 Cup Winners' Cup: 1967–68 Intercontinental Cup: 1969 ItalyUEFA European Football Championship: 1968 A. C. Milan Hall of Fame Profile at MagliaRossonera.it Profile at EmozioneCalcio.it International caps at FIGC.it
Peter White is an American actor. White was born in New York City, New York and studied acting at the prestigious Yale School of Drama. In 1968, White received critical acclaim for his role as Alan McCarthy in off-Broadway's The Boys in the Band. White, the rest of the original cast, appeared in the 1970 film version, directed by William Friedkin, he played Director of Central Intelligence John A. McCone in the film Thirteen Days. Among White's many television credits are appearances on The Feather and Father Gang, Ally McBeal, The West Wing, The Colbys, a recurring co-starring role as Dr. Thomas Reed on the television series Sisters and playing the role of Lincoln'Linc' Tyler off and on for over thirty years on the soap opera All My Children. In 2010 White appeared in filmmaker Crayton Robey's making-of The Boys in the Band documentary Making the Boys. Peter White on IMDb Peter White at AllMovie