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100-421: Lysine (symbol Lys or K ) is an α-amino acid that is a precursor to many proteins . Lysine contains an α-amino group (which is in the protonated −NH + 3 form when the lysine is dissolved in water at physiological pH ), an α-carboxylic acid group (which is in the deprotonated −COO form when the lysine is dissolved in water at physiological pH), and a side chain (CH 2 ) 4 NH 2 (which

200-509: A bilayer structure of phospholipids. The phospholipid molecule is amphipathic ; it contains a hydrophilic polar head and a hydrophobic nonpolar tail. The phospholipid heads interact with each other and aqueous media, while the hydrocarbon tails orient themselves in the center, away from water. These latter interactions drive the bilayer structure that acts as a barrier for ions and molecules. There are various types of phospholipids; consequently, their synthesis pathways differ. However,

300-469: A primer with a free 3'OH in which to incorporate nucleotides. In order for DNA replication to occur, a replication fork is created by enzymes called helicases which unwind the DNA helix. Topoisomerases at the replication fork remove supercoils caused by DNA unwinding, and single-stranded DNA binding proteins maintain the two single-stranded DNA templates stabilized prior to replication. DNA synthesis

400-454: A purine or pyrimidine base with a glycosidic bond and a phosphate group at the 5' location of the sugar. The DNA nucleotides adenosine and guanosine consist of a purine base attached to a ribose sugar with a glycosidic bond. In the case of RNA nucleotides deoxyadenosine and deoxyguanosine , the purine bases are attached to a deoxyribose sugar with a glycosidic bond. The purine bases on DNA and RNA nucleotides are synthesized in

500-446: A charged tRNA that is ready to add amino acids to the growing polypeptide chain. In addition to binding an amino acid, tRNA has a three nucleotide unit called an anticodon that base pairs with specific nucleotide triplets on the mRNA called codons ; codons encode a specific amino acid. This interaction is possible thanks to the ribosome, which serves as the site for protein synthesis. The ribosome possesses three tRNA binding sites:

600-450: A class of molecules called sterols . Sterols have four fused rings and a hydroxyl group . Cholesterol is a particularly important molecule. Not only does it serve as a component of lipid membranes, it is also a precursor to several steroid hormones, including cortisol , testosterone , and estrogen . Cholesterol is synthesized from acetyl CoA . The pathway is shown below: More generally, this synthesis occurs in three stages, with

700-538: A general base in catalysis . The ε- ammonium group ( −NH + 3 ) is attached to the fourth carbon from the α-carbon, which is attached to the carboxyl ( −COOH ) 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, anaemia, and systemic protein-energy deficiency. In contrast, an overabundance of lysine, caused by ineffective catabolism, can cause severe neurological disorders . Lysine

800-402: A hydrocarbon chain "tail". These fatty acids create larger components, which in turn incorporate noncovalent interactions to form the lipid bilayer. Fatty acid chains are found in two major components of membrane lipids: phospholipids and sphingolipids . A third major membrane component, cholesterol , does not contain these fatty acid units. The foundation of all biomembranes consists of

900-458: A polar head and nonpolar tails. Unlike phospholipids, sphingolipids have a sphingosine backbone. Sphingolipids exist in eukaryotic cells and are particularly abundant in the central nervous system . For example, sphingomyelin is part of the myelin sheath of nerve fibers. Sphingolipids are formed from ceramides that consist of a fatty acid chain attached to the amino group of a sphingosine backbone. These ceramides are synthesized from

1000-407: A precursor for carnitine , which transports fatty acids to the mitochondria , where they can be oxidised for the release of energy. Carnitine is synthesised from trimethyllysine , which is a product of the degradation of certain proteins, as such lysine must first be incorporated into proteins and be methylated prior to being converted to carnitine. However, in mammals the primary source of carnitine

1100-629: A process called translation . During translation, genetic material called mRNA is read by ribosomes to generate a protein polypeptide chain. This process requires transfer RNA (tRNA) which serves as an adaptor by binding amino acids on one end and interacting with mRNA at the other end; the latter pairing between the tRNA and mRNA ensures that the correct amino acid is added to the chain. Protein synthesis occurs in three phases: initiation, elongation, and termination. Prokaryotic ( archaeal and bacterial ) translation differs from eukaryotic translation ; however, this section will mostly focus on

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1200-431: A proton donor, to yield 2,3,4,5-tetrahydrodipicolinate (THDP). From this point on, four pathway variations have been found, namely the acetylase, aminotransferase, dehydrogenase, and succinylase pathways. Both the acetylase and succinylase variant pathways use four enzyme catalysed steps, the aminotransferase pathway uses two enzymes, and the dehydrogenase pathway uses a single enzyme. These four variant pathways converge at

1300-617: A reaction with acetyl-CoA . It can also be used to construct the amino acid alanine and can be converted into ethanol or lactic acid via fermentation . Pyruvic acid supplies energy to cells through the citric acid cycle (also known as the Krebs cycle) when oxygen is present ( aerobic respiration ), and alternatively ferments to produce lactate when oxygen is lacking. In 1834, Théophile-Jules Pelouze distilled tartaric acid and isolated glutaric acid and another unknown organic acid. Jöns Jacob Berzelius characterized this other acid

1400-510: A review by the European Food Safety Authority found no evidence of a cause–effect relationship. The same review, published in 2011, found no evidence to support claims that lysine could lower cholesterol, increase appetite, contribute to protein synthesis in any role other than as an ordinary nutrient, or increase calcium absorption or retention. Diseases related to lysine are a result of the downstream processing of lysine, i.e.

1500-412: A role in anaemia , as lysine is suspected to have an effect on the uptake of iron and, subsequently, the concentration of ferritin in blood plasma . However, the exact mechanism of action is yet to be elucidated. Most commonly, lysine deficiency is seen in non-western societies and manifests as protein-energy malnutrition , which has profound and systemic effects on the health of the individual. There

1600-423: A statistically significant difference in body weight with pyruvate compared to placebo . However, all of the trials had methodological weaknesses and the magnitude of the effect was small. The review also identified adverse events associated with pyruvate such as diarrhea, bloating, gas, and increase in low-density lipoprotein (LDL) cholesterol. The authors concluded that there was insufficient evidence to support

1700-406: A strong negative feedback loop on these enzymes and, subsequently, 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 also been reported that an alternative variant of

1800-457: A strong oxidizer (e.g., potassium permanganate or bleach ), or by the hydrolysis of acetyl cyanide , formed by reaction of acetyl chloride with potassium cyanide : Pyruvate is an important chemical compound in biochemistry . It is the output of the metabolism of glucose known as glycolysis . One molecule of glucose breaks down into two molecules of pyruvate, which are then used to provide further energy, in one of two ways. Pyruvate

1900-493: A twelve-step reaction mechanism present in most single-celled organisms. Higher eukaryotes employ a similar reaction mechanism in ten reaction steps. Purine bases are synthesized by converting phosphoribosyl pyrophosphate (PRPP) to inosine monophosphate (IMP), which is the first key intermediate in purine base biosynthesis. Further enzymatic modification of IMP produces the adenosine and guanosine bases of nucleotides. Other DNA and RNA nucleotide bases that are linked to

2000-417: A variant AAA pathway found in some prokaryotes, AAA is first converted to N ‑acetyl-α-aminoadipate, which is phosphorylated and then reductively dephosphorylated to the ε-aldehyde. The aldehyde is then transaminated to N ‑acetyllysine, which is deacetylated to give L -lysine. However, the enzymes involved in this variant pathway need further validation. As with all amino acids, catabolism of lysine

2100-440: Is hydrolysed by the same enzyme to produce homocitrate . Homocitrate is enzymatically dehydrated by homoaconitase (HAc) (E.C 4.2.1.36) to yield cis -homoaconitate . HAc then catalyses a second reaction in which cis -homoaconitate undergoes rehydration to produce homoisocitrate . The resulting product undergoes an oxidative decarboxylation by homoisocitrate dehydrogenase (HIDH) (E.C 1.1.1.87) to yield α‑ketoadipate. AAA

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2200-553: 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. The most common bacteria used is Corynebacterium glutamicum specially mutagenized or gene-engineered to produce lysine, but analogous strains of Escherichia coli are also employed. The 1993 film Jurassic Park , which

2300-411: Is a two-step reaction which involves the conversion of UMP to UTP . Phosphate addition to UMP is catalyzed by a kinase enzyme. The enzyme CTP synthase catalyzes the next reaction step: the conversion of UTP to CTP by transferring an amino group from glutamine to uridine; this forms the cytosine base of CTP. The mechanism, which depicts the reaction UTP + ATP + glutamine ⇔ CTP + ADP + glutamate,

2400-481: Is activated by a phosphopantetheinyl transferase (E.C 2.7.8.7). Once the semialdehyde is formed, saccharopine reductase (E.C 1.5.1.10) catalyses a condensation reaction with glutamate and NAD(P)H, as a proton donor, and the imine is reduced to produce the penultimate product, saccharopine. The final step of the pathway in fungi involves the saccharopine dehydrogenase (SDH) (E.C 1.5.1.8) catalysed oxidative deamination of saccharopine, resulting in L -lysine. In

2500-485: Is also a hereditary genetic disease that involves mutations in the enzymes responsible for lysine catabolism, namely the bifunctional AASS enzyme of the saccharopine pathway. Due to a lack of lysine catabolism, the amino acid accumulates in plasma and patients develop hyperlysinaemia , which can present as asymptomatic to severe neurological disabilities , including epilepsy , ataxia , spasticity , and psychomotor impairment . The clinical significance of hyperlysinemia

2600-478: Is an essential amino acid . 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

2700-413: 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

2800-426: Is attributed to an opaque-2 mutation that reduced the transcription of lysine-lacking zein -related seed storage proteins and, as a result, increased the abundance of other proteins that are rich in lysine. Commonly, to overcome the limiting abundance of lysine in livestock feed, industrially produced lysine is added. The industrial process includes the fermentative culturing of Corynebacterium glutamicum and

2900-456: Is based on the 1990 novel Jurassic Park by Michael Crichton , features dinosaurs that were genetically altered so that they could not produce lysine, an example of engineered auxotrophy . This was known as the "lysine contingency" and was supposed to prevent the cloned dinosaurs from surviving outside the park, forcing them to depend on lysine supplements provided by the park's veterinary staff. In reality, no animal can produce lysine; it

3000-447: Is below: Cytosine is a nucleotide that is present in both DNA and RNA. However, uracil is only found in RNA. Therefore, after UTP is synthesized, it is must be converted into a deoxy form to be incorporated into DNA. This conversion involves the enzyme ribonucleoside triphosphate reductase . This reaction that removes the 2'-OH of the ribose sugar to generate deoxyribose is not affected by

3100-442: Is catalyzed by the enzyme phosphoserine phosphatase , which dephosphorylates L-phosphoserine to yield L-serine . There are two known pathways for the biosynthesis of glycine. Organisms that use ethanol and acetate as the major carbon source utilize the glyconeogenic pathway to synthesize glycine . The other pathway of glycine biosynthesis is known as the glycolytic pathway. This pathway converts serine synthesized from

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3200-403: Is catalyzed by the enzyme pyrroline-5-carboxylate synthase (P5CS), which catalyzes the reduction of the ϒ-carboxyl group of L-glutamate 5-phosphate. This results in the formation of glutamate semialdehyde, which spontaneously cyclizes to pyrroline-5-carboxylate. Pyrroline-5-carboxylate is further reduced by the enzyme pyrroline-5-carboxylate reductase (P5CR) to yield a proline amino acid. In

3300-489: Is commonly met in a western society with the intake of lysine from meat and vegetable sources well in excess of the recommended requirement. In vegetarian diets, the intake of lysine is less due to the limited quantity of lysine in cereal crops compared to meat sources. Given the limiting concentration of lysine in cereal crops, it has long been speculated that the content of lysine can be increased through genetic modification practices. Often these practices have involved

3400-410: Is composed of nucleotides that are joined by phosphodiester bonds . DNA synthesis , which takes place in the nucleus , is a semiconservative process, which means that the resulting DNA molecule contains an original strand from the parent structure and a new strand. DNA synthesis is catalyzed by a family of DNA polymerases that require four deoxynucleoside triphosphates, a template strand , and

3500-437: Is contained in 1.25 g of L -lysine HCl. The most common role for lysine is proteinogenesis. Lysine frequently plays an important role in protein structure . Since its side chain contains a positively charged group on one end and a long hydrophobic carbon tail close to the backbone, lysine is considered somewhat amphipathic . For this reason, lysine can be found buried as well as more commonly in solvent channels and on

3600-450: Is converted by fermentation to lactate using the enzyme lactate dehydrogenase and the coenzyme NADH in lactate fermentation , or to acetaldehyde (with the enzyme pyruvate decarboxylase ) and then to ethanol in alcoholic fermentation . Pyruvate is a key intersection in the network of metabolic pathways . Pyruvate can be converted into carbohydrates via gluconeogenesis , to fatty acids or energy through acetyl-CoA , to

3700-459: Is converted into acetyl-coenzyme A , which is the main input for a series of reactions known as the Krebs cycle (also known as the citric acid cycle or tricarboxylic acid cycle). Pyruvate is also converted to oxaloacetate by an anaplerotic reaction , which replenishes Krebs cycle intermediates; also, the oxaloacetate is used for gluconeogenesis . These reactions are named after Hans Adolf Krebs ,

3800-412: Is converted to phosphatidate via the addition of another fatty acid chain contributed by a second acyl CoA; all of these steps are catalyzed by the glycerol phosphate acyltransferase enzyme. Phospholipid synthesis continues in the endoplasmic reticulum, and the biosynthesis pathway diverges depending on the components of the particular phospholipid. Like phospholipids, these fatty acid derivatives have

3900-409: Is found in both prokaryotes and plants and begins with the dihydrodipicolinate synthase (DHDPS) (E.C 4.3.3.7) catalysed condensation reaction between the aspartate derived, L -aspartate semialdehyde, and pyruvate to form (4 S )-4-hydroxy-2,3,4,5-tetrahydro-(2 S )-dipicolinic acid (HTPA). The product is then reduced by dihydrodipicolinate reductase (DHDPR) (E.C 1.3.1.26), with NAD(P)H as

4000-446: Is initiated by the RNA polymerase primase , which makes an RNA primer with a free 3'OH. This primer is attached to the single-stranded DNA template, and DNA polymerase elongates the chain by incorporating nucleotides; DNA polymerase also proofreads the newly synthesized DNA strand. During the polymerization reaction catalyzed by DNA polymerase, a nucleophilic attack occurs by the 3'OH of

4100-418: Is initiated from the uptake of dietary lysine or from the breakdown of intracellular protein. Catabolism is also used as a means to control the intracellular concentration of free lysine and maintain a steady-state to prevent the toxic effects of excessive free lysine. There are several pathways involved in lysine catabolism but the most commonly used is the saccharopine pathway, which primarily takes place in

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4200-547: Is made discontinuously in Okazaki fragments and grows away from the replication fork. Okazaki fragments are covalently joined by DNA ligase to form a continuous strand. Then, to complete DNA replication, RNA primers are removed, and the resulting gaps are replaced with DNA and joined via DNA ligase. A protein is a polymer that is composed from amino acids that are linked by peptide bonds . There are more than 300 amino acids found in nature of which only twenty two, known as

4300-414: Is marked by high amounts of lysine in the urine. It is often due to a metabolic disease in which a protein involved in the breakdown of lysine is non functional due to a genetic mutation. It may also occur due to a failure of renal tubular transport. Lysine production for animal feed is a major global industry, reaching in 2009 almost 700,000 tons for a market value of over €1.22 billion. Lysine

4400-418: Is partially protonated when the lysine is dissolved in water at physiological pH), and so it is classified as a basic , charged (in water at physiological pH), aliphatic amino acid. It is encoded by the codons AAA and AAG. Like almost 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

4500-534: Is plentiful in most pulses (legumes). Beans contain the lysine that maize lacks, and in the human archeological record beans and maize often appear together, as in the Three Sisters : beans, maize, and squash. 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). L -lysine HCl is used as a dietary supplement , providing 80.03% L -lysine. As such, 1 g of L -lysine

4600-469: Is responsible for synthesizing thymine residues from dUMP to dTMP . This reaction transfers a methyl group onto the uracil base of dUMP to generate dTMP. The thymidylate synthase reaction, dUMP + 5,10-methylenetetrahydrofolate ⇔ dTMP + dihydrofolate, is shown to the right. Although there are differences between eukaryotic and prokaryotic DNA synthesis, the following section denotes key characteristics of DNA replication shared by both organisms. DNA

4700-509: Is responsible for the decarboxylation reaction. Finally, glutaryl-CoA is oxidatively decarboxylated to crotonyl-CoA by glutaryl-CoA dehydrogenase (E.C 1.3.8.6), which goes on to be further processed through multiple enzymatic steps to yield acetyl-CoA; an essential carbon metabolite involved in the tricarboxylic acid cycle (TCA) . Lysine is an essential amino acid in humans. The human daily nutritional requirement varies from ~60 mg/kg in infancy to ~30 mg/kg in adults. This requirement

4800-431: Is synthesized by an ATP-dependent addition of an amino group onto aspartate; asparagine synthetase catalyzes the addition of nitrogen from glutamine or soluble ammonia to aspartate to yield asparagine. The diaminopimelic acid biosynthetic pathway of lysine belongs to the aspartate family of amino acids. This pathway involves nine enzyme-catalyzed reactions that convert aspartate to lysine. Protein synthesis occurs via

4900-400: Is the simplest of the alpha-keto acids , with a carboxylic acid and a ketone functional group. Pyruvate , the conjugate base , CH 3 COCOO , is an intermediate in several metabolic pathways throughout the cell. Pyruvic acid can be made from glucose through glycolysis , converted back to carbohydrates (such as glucose) via gluconeogenesis , or converted to fatty acids through

5000-438: Is the subject of debate in the field with some studies finding no correlation between physical or mental disabilities and hyperlysinemia. In addition to this, mutations in genes related to lysine metabolism have been implicated in several disease states, including pyridoxine-dependent epilepsia ( ALDH7A1 gene ), α-ketoadipic and α-aminoadipic aciduria ( DHTKD1 gene ), and glutaric aciduria type 1 ( GCDH gene ). Hyperlysinuria

5100-487: Is then formed via a pyridoxal 5′-phosphate (PLP) -dependent aminotransferase (PLP-AT) (E.C 2.6.1.39), using glutamate as the amino donor. From this point on, the AAA pathway varies with [something is missing here ? -> at the very least, section header! ] on the kingdom. In fungi, AAA is reduced to α‑aminoadipate-semialdehyde via AAA reductase (E.C 1.2.1.95) in a unique process involving both adenylation and reduction that

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5200-499: Is through dietary sources, rather than through lysine conversion. 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). There has been a long discussion that lysine, when administered intravenously or orally, can significantly increase

5300-420: The acylation of sphingosine. The biosynthetic pathway for sphingosine is found below: As the image denotes, during sphingosine synthesis, palmitoyl CoA and serine undergo a condensation reaction which results in the formation of 3-dehydrosphinganine. This product is then reduced to form dihydrospingosine, which is converted to sphingosine via the oxidation reaction by FAD . This lipid belongs to

5400-681: The amino acid alanine , and to ethanol . Therefore, it unites several key metabolic processes. In the last step of glycolysis , phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase . This reaction is strongly exergonic and irreversible; in gluconeogenesis , it takes two enzymes, pyruvate carboxylase and PEP carboxykinase , to catalyze the reverse transformation of pyruvate to PEP. Compound C00074 at KEGG Pathway Database. Enzyme 2.7.1.40 at KEGG Pathway Database. Compound C00022 at KEGG Pathway Database. Click on genes, proteins and metabolites below to link to respective articles. Pyruvate decarboxylation by

5500-478: The crosslinking between the three helical polypeptides in collagen , resulting in its stability and tensile strength. This mechanism is akin to the role of lysine in bacterial cell walls , in which lysine (and meso -diaminopimelate) are critical to the formation of crosslinks, and therefore, stability of the cell wall. This concept has previously been explored as a means to circumvent the unwanted release of potentially pathogenic genetically modified bacteria. It

5600-532: The liver (and equivalent organs) in animals, specifically within the mitochondria . This is the reverse of the previously described AAA pathway. In animals and plants, the first two steps of the saccharopine pathway are catalysed by the bifunctional enzyme, α-aminoadipic semialdehyde synthase (AASS) , which possess both lysine-ketoglutarate reductase (LKR) (E.C 1.5.1.8) and SDH activities, whereas in other organisms, such as bacteria and fungi, both of these enzymes are encoded by separate genes . The first step involves

5700-519: The proteinogenic amino acids , are the building blocks for protein. Only green plants and most microbes are able to synthesize all of the 20 standard amino acids that are needed by all living species. Mammals can only synthesize ten of the twenty standard amino acids. The other amino acids, valine , methionine , leucine , isoleucine , phenylalanine , lysine , threonine and tryptophan for adults and histidine , and arginine for babies are obtained through diet. The general structure of

5800-494: The pyruvate dehydrogenase complex produces acetyl-CoA . Carboxylation by pyruvate carboxylase produces oxaloacetate . Transamination by alanine transaminase produces alanine . Reduction by lactate dehydrogenase produces lactate . Pyruvic acid is an abundant carboxylic acid in secondary organic aerosols . Pyruvate is sold as a weight-loss supplement , though credible science has yet to back this claim. A systematic review of six trials found

5900-493: The AAA biosynthesis pathway, resulting in AAA being converted to α-ketoadipate. The product, α‑ketoadipate, is decarboxylated in the presence of NAD and coenzyme A to yield glutaryl-CoA, however the enzyme involved in this is yet to be fully elucidated. Some evidence suggests that the 2-oxoadipate dehydrogenase complex (OADHc), which is structurally homologous to the E1 subunit of the oxoglutarate dehydrogenase complex (OGDHc) (E.C 1.2.4.2),

6000-463: The AAA route has been found in Thermus thermophilus and Pyrococcus horikoshii , which could indicate that this pathway is more widely spread in prokaryotes than originally 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 (HCS) (E.C 2.3.3.14) to give the intermediate homocitryl‑CoA, which

6100-465: The LKR catalysed reduction of L -lysine in the presence of α-ketoglutarate to produce saccharopine, with NAD(P)H acting as a proton donor. Saccharopine then undergoes a dehydration reaction, catalysed by SDH in the presence of NAD , to produce AAS and glutamate. AAS dehydrogenase (AASD) (E.C 1.2.1.31) then further dehydrates the molecule into AAA. Subsequently, PLP-AT catalyses the reverse reaction to that of

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6200-473: The N-acetyl-L-ornithine. The acetyl group of acetylornithine is removed by the enzyme acetylornithinase (AO) or ornithine acetyltransferase (OAT), and this yields ornithine . Then, the enzymes citrulline and argininosuccinate convert ornithine to arginine. There are two distinct lysine biosynthetic pathways: the diaminopimelic acid pathway and the α-aminoadipate pathway . The most common of

6300-414: The amino acid lysine , which is derived from α-ketoglutarate . The biosynthesis of glutamate and glutamine is a key step in the nitrogen assimilation discussed above. The enzymes GOGAT and GDH catalyze the nitrogen assimilation reactions. In bacteria, the enzyme glutamate 5-kinase initiates the biosynthesis of proline by transferring a phosphate group from ATP onto glutamate. The next reaction

6400-552: The aminoacyl site (A site), the peptidyl site (P site), and the exit site (E site). There are numerous codons within an mRNA transcript, and it is very common for an amino acid to be specified by more than one codon; this phenomenon is called degeneracy . In all, there are 64 codons, 61 of each code for one of the 20 amino acids, while the remaining codons specify chain termination. As previously mentioned, translation occurs in three phases: initiation, elongation, and termination. Pyruvic acid Pyruvic acid (CH 3 COCOOH)

6500-499: The aspartate family even though part of their carbon skeleton is derived from pyruvate . In the case of methionine, the methyl carbon is derived from serine and the sulfur group, but in most organisms, it is derived from cysteine. The biosynthesis of aspartate is a one step reaction that is catalyzed by a single enzyme. The enzyme aspartate aminotransferase catalyzes the transfer of an amino group from aspartate onto α-ketoglutarate to yield glutamate and oxaloacetate . Asparagine

6600-455: The bases attached to the sugar. This non-specificity allows ribonucleoside triphosphate reductase to convert all nucleotide triphosphates to deoxyribonucleotide by a similar mechanism. In contrast to uracil, thymine bases are found mostly in DNA, not RNA. Cells do not normally contain thymine bases that are linked to ribose sugars in RNA, thus indicating that cells only synthesize deoxyribose-linked thymine. The enzyme thymidylate synthetase

6700-493: The biochemist awarded the 1953 Nobel Prize for physiology, jointly with Fritz Lipmann , for research into metabolic processes. The cycle is also known as the citric acid cycle or tricarboxylic acid cycle, because citric acid is one of the intermediate compounds formed during the reactions. If insufficient oxygen is available, the acid is broken down anaerobically , creating lactate in animals and ethanol in plants and microorganisms (and in carp ). Pyruvate from glycolysis

6800-489: The biologically active enantiomer L -lysine, where the α-carbon is in the S configuration. The human body cannot synthesize lysine. It is essential in humans and must therefore be obtained from the diet. In organisms that synthesise lysine, two main biosynthetic pathways exist, the diaminopimelate and α-aminoadipate pathways, which employ distinct enzymes and substrates and are found in diverse organisms. Lysine catabolism occurs through one of several pathways,

6900-403: The building blocks for macromolecules. Some important biological macromolecules include: proteins , which are composed of amino acid monomers joined via peptide bonds , and DNA molecules, which are composed of nucleotides joined via phosphodiester bonds . Biosynthesis occurs due to a series of chemical reactions. For these reactions to take place, the following elements are necessary: In

7000-461: The carbons needed for the biosynthesis of the methionine and histidine . During serine biosynthesis, the enzyme phosphoglycerate dehydrogenase catalyzes the initial reaction that oxidizes 3-phospho-D-glycerate to yield 3-phosphonooxypyruvate . The following reaction is catalyzed by the enzyme phosphoserine aminotransferase , which transfers an amino group from glutamate onto 3-phosphonooxypyruvate to yield L-phosphoserine . The final step

7100-408: The commonalities between the two organisms. Before translation can begin, the process of binding a specific amino acid to its corresponding tRNA must occur. This reaction, called tRNA charging, is catalyzed by aminoacyl tRNA synthetase . A specific tRNA synthetase is responsible for recognizing and charging a particular amino acid. Furthermore, this enzyme has special discriminator regions to ensure

7200-842: 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 gave the basis for the book The Informant: A True Story , and the movie The Informant! . [REDACTED] This article was adapted from the following source under a CC BY 4.0 license ( 2018 ) ( reviewer reports ): Cody J Hall; Tatiana P. Soares da Costa (1 June 2018). "Lysine: biosynthesis, catabolism and roles" (PDF) . WikiJournal of Science . 1 (1): 4. doi : 10.15347/WJS/2018.004 . ISSN   2470-6345 . Wikidata   Q55120301 . Biosynthesis Elements of biosynthesis include: precursor compounds, chemical energy (e.g. ATP ), and catalytic enzymes which may need coenzymes (e.g. NADH , NADPH ). These elements create monomers ,

7300-411: The correct binding between tRNA and its cognate amino acid. The first step for joining an amino acid to its corresponding tRNA is the formation of aminoacyl-AMP: This is followed by the transfer of the aminoacyl group from aminoacyl-AMP to a tRNA molecule. The resulting molecule is aminoacyl-tRNA : The combination of these two steps, both of which are catalyzed by aminoacyl tRNA synthetase, produces

7400-613: The edible component of cereal crops. This highlights the need to not only increase free lysine, but also direct lysine towards the synthesis of stable seed storage proteins, and subsequently, increase the nutritional value of the consumable component of crops. While genetic modification practices have met limited success, more traditional selective breeding techniques have allowed for the isolation of " Quality Protein Maize ", which has significantly increased levels of lysine and tryptophan , also an essential amino acid. This increase in lysine content

7500-474: The enzyme glutamate dehydrogenase (GDH). GDH is able to transfer ammonia onto 2-oxoglutarate and form glutamate. Furthermore, the enzyme glutamine synthetase (GS) is able to transfer ammonia onto glutamate and synthesize glutamine, replenishing glutamine. The glutamate family of amino acids includes the amino acids that derive from the amino acid glutamate. This family includes: glutamate, glutamine , proline , and arginine . This family also includes

7600-409: The enzyme glutamine oxoglutarate aminotransferase (GOGAT) which removes the amide amino group of glutamine and transfers it onto 2-oxoglutarate , producing two glutamate molecules. In this catalysis reaction, glutamine serves as the nitrogen source. An image illustrating this reaction is found to the right. The other pathway for incorporating nitrogen onto the α-carbon of amino acids involves

7700-468: The enzyme serine acetyltransferase catalyzes the transfer of acetyl group from acetyl-CoA onto L-serine to yield O-acetyl-L-serine . The following reaction step, catalyzed by the enzyme O-acetyl serine (thiol) lyase , replaces the acetyl group of O-acetyl-L-serine with sulfide to yield cysteine. The aspartate family of amino acids includes: threonine , lysine , methionine , isoleucine , and aspartate. Lysine and isoleucine are considered part of

7800-463: The exterior of proteins, where it can interact with the aqueous environment. Lysine can also contribute to protein stability as its ε-amino group often participates in hydrogen bonding , salt bridges and covalent interactions to form a Schiff base . A second major role of lysine is in epigenetic regulation by means of histone modification . There are several types of covalent histone modifications, which commonly involve lysine residues found in

7900-475: The first stage taking place in the cytoplasm and the second and third stages occurring in the endoplasmic reticulum. The stages are as follows: The biosynthesis of nucleotides involves enzyme- catalyzed reactions that convert substrates into more complex products. Nucleotides are the building blocks of DNA and RNA . Nucleotides are composed of a five-membered ring formed from ribose sugar in RNA, and deoxyribose sugar in DNA; these sugars are linked to

8000-409: The first step in phospholipid synthesis involves the formation of phosphatidate or diacylglycerol 3-phosphate at the endoplasmic reticulum and outer mitochondrial membrane . The synthesis pathway is found below: The pathway starts with glycerol 3-phosphate, which gets converted to lysophosphatidate via the addition of a fatty acid chain provided by acyl coenzyme A . Then, lysophosphatidate

8100-552: The first step of arginine biosynthesis in bacteria, glutamate is acetylated by transferring the acetyl group from acetyl-CoA at the N-α position; this prevents spontaneous cyclization. The enzyme N-acetylglutamate synthase (glutamate N-acetyltransferase) is responsible for catalyzing the acetylation step. Subsequent steps are catalyzed by the enzymes N-acetylglutamate kinase , N-acetyl-gamma-glutamyl-phosphate reductase , and acetylornithine/succinyldiamino pimelate aminotransferase and yield

8200-421: The following year and named pyruvic acid because it was distilled using heat. The correct molecular structure was deduced by the 1870s. Pyruvic acid is a colorless liquid with a smell similar to that of acetic acid and is miscible with water. In the laboratory, pyruvic acid may be prepared by heating a mixture of tartaric acid and potassium hydrogen sulfate , by the oxidation of propylene glycol by

8300-432: The formation of the penultimate product, meso ‑diaminopimelate, which is subsequently enzymatically decarboxylated in an irreversible reaction catalysed by diaminopimelate decarboxylase (DAPDC) (E.C 4.1.1.20) 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

8400-400: The growing chain on the innermost phosphorus atom of a deoxynucleoside triphosphate; this yields the formation of a phosphodiester bridge that attaches a new nucleotide and releases pyrophosphate . Two types of strands are created simultaneously during replication: the leading strand , which is synthesized continuously and grows towards the replication fork, and the lagging strand , which

8500-580: The incorporation into proteins or modification into alternative biomolecules. The role of lysine in collagen has been outlined above, however, a lack of lysine and hydroxylysine involved in the crosslinking of collagen peptides has been linked to a disease state of the connective tissue. As carnitine is a key lysine-derived metabolite involved in fatty acid metabolism, a substandard diet lacking sufficient carnitine and lysine can lead to decreased carnitine levels, which can have significant cascading effects on an individual's health. Lysine has also been shown to play

8600-561: The intentional dysregulation of the DAP pathway by means of introducing lysine feedback-insensitive orthologues of the DHDPS enzyme. These methods have met limited success likely due to the toxic side effects of increased free lysine and indirect effects on the TCA cycle. Plants accumulate lysine and other amino acids in the form of seed storage proteins , found within the seeds of the plant, and this represents

8700-419: The intermediates of glycolysis to glycine. In the glycolytic pathway, the enzyme serine hydroxymethyltransferase catalyzes the cleavage of serine to yield glycine and transfers the cleaved carbon group of serine onto tetrahydrofolate , forming 5,10-methylene-tetrahydrofolate . Cysteine biosynthesis is a two-step reaction that involves the incorporation of inorganic sulfur . In microorganisms and plants,

8800-406: The intestine, reclaimed in the kidney, and moved into cells by the same amino acid transporters , an abundance of lysine would, in theory, limit the amount of arginine available for viral replication. Clinical studies do not provide good evidence for effectiveness as a prophylactic or in the treatment for HSV outbreaks. In response to product claims that lysine could improve immune responses to HSV,

8900-463: The most common of which is the saccharopine pathway . Lysine plays several roles in humans, most importantly proteinogenesis , but also in the crosslinking of collagen polypeptides, uptake of essential mineral nutrients, and in the production of carnitine , which is key in fatty acid metabolism . Lysine is also often involved in histone modifications , and thus, impacts the epigenome . The ε-amino group often participates in hydrogen bonding and as

9000-582: The protruding tail of histones. Modifications often include the addition or removal of an acetyl (−CH 3 CO) forming acetyllysine or reverting to lysine, up to three methyl (−CH 3 ) , ubiquitin or a sumo protein group. The various modifications have downstream effects on gene regulation , in which genes can be activated or repressed. Lysine has also been implicated to play a key role in other biological processes including; structural proteins of connective tissues , calcium homeostasis , and fatty acid metabolism . Lysine has been shown to be involved in

9100-433: The release of growth hormones . This has led to athletes using lysine as a means of promoting muscle growth while training, however, no significant evidence to support this application of lysine has been found to date. Because herpes simplex virus (HSV) proteins are richer in arginine and poorer in lysine than the cells they infect, lysine supplements have been tried as a treatment. Since the two amino acids are taken up in

9200-456: The ribose sugar via a glycosidic bond are thymine , cytosine and uracil (which is only found in RNA). Uridine monophosphate biosynthesis involves an enzyme that is located in the mitochondrial inner membrane and multifunctional enzymes that are located in the cytosol . After the uridine nucleotide base is synthesized, the other bases, cytosine and thymine are synthesized. Cytosine biosynthesis

9300-426: The simplest sense, the reactions that occur in biosynthesis have the following format: Some variations of this basic equation which will be discussed later in more detail are: Many intricate macromolecules are synthesized in a pattern of simple, repeated structures. For example, the simplest structures of lipids are fatty acids . Fatty acids are hydrocarbon derivatives; they contain a carboxyl group "head" and

9400-419: The standard amino acids includes a primary amino group , a carboxyl group and the functional group attached to the α-carbon . The different amino acids are identified by the functional group. As a result of the three different groups attached to the α-carbon, amino acids are asymmetrical molecules . For all standard amino acids, except glycine , the α-carbon is a chiral center . In the case of glycine,

9500-417: The structurally simpler leucine, and M to methionine. Two pathways have been identified in nature for the synthesis of lysine. The diaminopimelate (DAP) pathway belongs to the aspartate derived biosynthetic family, which is also involved in the synthesis of threonine , methionine and isoleucine , whereas the α-aminoadipate (AAA) pathway is part of the glutamate biosynthetic family. The DAP pathway

9600-410: The subsequent purification of lysine. 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

9700-409: The two synthetic pathways is the diaminopimelic acid pathway; it consists of several enzymatic reactions that add carbon groups to aspartate to yield lysine: The serine family of amino acid includes: serine, cysteine , and glycine . Most microorganisms and plants obtain the sulfur for synthesizing methionine from the amino acid cysteine. Furthermore, the conversion of serine to glycine provides

9800-520: The α-carbon has two hydrogen atoms, thus adding symmetry to this molecule. With the exception of proline , all of the amino acids found in life have the L-isoform conformation. Proline has a functional group on the α-carbon that forms a ring with the amino group. One major step in amino acid biosynthesis involves incorporating a nitrogen group onto the α-carbon. In cells, there are two major pathways of incorporating nitrogen groups. One pathway involves

9900-498: Was first isolated by the German biological chemist Ferdinand Heinrich Edmund Drechsel in 1889 from hydrolysis of the protein casein , and thus named it Lysin, from Greek λύσις (lysis)  'loosening'. In 1902, the German chemists Emil Fischer and Fritz Weigert determined lysine's chemical structure by synthesizing it. The one-letter symbol K was assigned to lysine for being alphabetically nearest, with L being assigned to

10000-449: Was proposed that an auxotrophic strain of Escherichia coli ( X 1776) could be used for all genetic modification practices, as the strain is unable to survive without the supplementation of DAP, and thus, cannot live outside of a laboratory environment. Lysine has also been proposed to be involved in calcium intestinal absorption and renal retention, and thus, may play a role in calcium homeostasis . Finally, lysine has been shown to be

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