Amino acid synthesis is a series of biochemical processes (metabolic pathways) in which various amino acids are produced from other compounds. Substrates for this process are various compounds in the food or growth medium of the organism. Not all organisms are able to synthesize all amino acids. Humans are a good example of this, because humans can only synthesize 11 of the 20 standard amino acids (ie non-essential amino acids), and at the time of accelerated growth, histidine can be considered an essential amino acid.
The fundamental problem for biological systems is to get nitrogen in a convenient form. This problem is solved by certain microorganisms capable of reducing an inert N (N) molecule (nitrogen gas) into two ammonia molecules in one of the most remarkable reactions in biochemistry. Ammonia is the source of nitrogen for all amino acids. Carbon backbones come from the glycolytic pathway, the phosphate pentose pathway, or the citric acid cycle.
In the production of amino acids, one finds an important problem in biosynthesis, ie stereochemical control. Since all amino acids except glycine are chiral, the biosynthetic pathway must produce the correct isomer with high fidelity. In each of the 19 pathways for the formation of chiral amino acids, the stereochemistry of carbonic atoms is formed by transamination reactions involving pyridoxal phosphates. Almost all of the transaminases that catalyze this reaction descend from the same ancestor, illustrating once again that effective solutions to biochemical problems are maintained throughout evolution.
Biosynthetic pathways are often highly regulated in such a way that block-building is synthesized only when supplies are low. Very often, high concentrations of end products from pathways inhibit the activity of enzymes that function at the beginning of the pathway. Often present are allosteric enzymes that are able to sense and respond to the concentration of regulating species. This enzyme is similar in functional properties to aspartate transcarbamoylase and its regulators. Feedback and allosteric mechanisms ensure that all twenty amino acids are maintained in sufficient quantities for protein synthesis and other processes.
Video Amino acid synthesis
Fiksasi nitrogen
Microorganisms use ATP and reduce ferredoxin, a powerful reductor, to reduce atmospheric nitrogen (N 2 ) to ammonia (NH 3 ). An iron-molybdenum group in nitrogenase by agile catalyzes the fixation of N 2 , an inert molecule. Higher organisms consume fixed nitrogen to synthesize amino acids, nucleotides, and other nitrogen-containing biomolecules. The main points of entry of ammonia into metabolism are glutamine or glutamate.
Maps Amino acid synthesis
Transamination
Most of the amino acids are synthesized from? -ketoacids, and then transaminated from other amino acids, usually glutamate. The enzyme involved in this reaction is aminotransferase.
- ? - ketoacid glutamate? amino acid ? -ketoglutarat
Glutamat sendiri dibentuk oleh aminasi? -ketoglutarat:
- ? - ketoglutarate NH
< sub style = "font-size: inherit; line-height: inherit; vertical-align: baseline"> 4 ? glutamat
Dari intermediet siklus asam sitrat dan jalur lainnya
From the basic set of twenty amino acids (excluding selenocysteine), there are eight that can not be synthesized by humans. In addition, amino acids arginine, cysteine, glycine, glutamine, histidine, proline, serine, and tyrosine are considered important conditional , meaning they are usually not required in the diet, but must be exogenously assigned to specific populations not synthesize it in sufficient quantities. For example, enough arginine is synthesized by the urea cycle to meet the needs of adults but perhaps not from growing children. Amino acids that must be obtained from the diet are called essential amino acids. Non-essential amino acids are produced in the body. The pathway for the synthesis of nonessential amino acids is quite simple. Glutamate dehydrogenase catalyzes the reductive amination of the -ketoglutarate into glutamate. The transamination reaction occurs in the synthesis of most amino acids. In this step, the chirality of amino acids is formed. Alanine and aspartate are synthesized by transamination of pyruvate and oxaloacetate, respectively. Glutamine is synthesized from NH4 and glutamate, and asparagine is synthesized similarly. Proline and arginine are derived from glutamate. Serine, formed from 3-phosphoglycerate, is a precursor of glycine and cysteine. Tyrosine is synthesized by hydroxylation of phenylalanine, an essential amino acid. Pathways for the biosynthesis of essential amino acids are much more complex than those for nonessential ones. Active tetrahydrofolate, the carrier of a one-carbon unit, plays an important role in the metabolism of amino acids and nucleotides. This coenzyme carries a one-carbon unit of three oxidation states, which can be interchanged: at most minus - methyl; medium - methylene; and most oxidized - formyl, formimino, and methenyl. The main donor of the active methyl group is S-adenosylmethionine, which is synthesized by transfer of adenosyl groups from ATP to methionine sulfur atoms. S-Adenosylhomocysteine ​​is formed when the activated methyl group is transferred to the acceptor. It is hydrolyzed to adenosine and homocysteine, the latter being subsequently methylated to methionine to complete the activated methyl cycle.
Cortisol inhibits protein synthesis.
Rule with feedback inhibition
Most of the amino acid biosynthesis pathways are regulated by feedback inhibition, in which allosterically committed steps are inhibited by the final product. Branch paths require extensive interaction between branches that include negative and positive regulation. The regulation of glutamine synthetase from E. coli is a striking demonstration of inhibition of cumulative feedback and control by a reversible covalent cascade modification.
? - Ketoglutarate
Family synthesis of amino acids -ketoglutarate (synthesis of glutamate, glutamine, proline and arginine) begins with? -ketoglutarate, intermediates in the Citrate Cycle. Concentration? -ketoglutarat depends on the activity and metabolism in the cell along with the regulation of enzymatic activity. In E. coli citrate synthase, the enzyme involved in the condensation reaction initiates the Citric Acid Cycle is severely inhibited by the inhibition of aqueous -ketoglutarate and can be inhibited by DPNH as well as high concentrations of ATP. This is one of the earliest regulations of the family of amino acid synthesis -ketoglutarate.
Setting the synthesis of glutamate from? -ketoglutarate is subject to regulatory control of the Citric Cycle as well as the action of mass depending on the concentration of reactants involved due to the reversible nature of the transamination and glutamate dehydrogenase reaction.
Conversion of glutamate into glutamine is regulated by glutamine synthetase (GS) and is a very significant step in nitrogen metabolism. This enzyme is governed by at least four different mechanisms: 1. Repression and depression due to nitrogen levels; 2. Activation and inactivation due to enzymatic form (fast and relaxed); 3. Inhibition of cumulative feedback through metabolite end products; and 4. Enzyme changes due to adenilasi and deadenylation. In rich nitrogen media or growth conditions containing high amounts of ammonia there is a low GS level, whereas in limiting the amount of ammonia, the specific activity of the enzyme is 20-fold higher. Confirmation of enzymes plays a role in regulation depending on whether GS is in tight or relaxed form. The GS form is tightly fully active, but the removal of the manganese turns the enzyme into a relaxed state. The specific conformation state occurs based on the binding of specific divalent cations and is also associated with adenilation. Inhibition of GS feedback is due to cumulative feedback due to several metabolites including L-tryptophan, L-histidine, AMP, CTP, glucosamine-6-phosphate and carbamate phosphate, alanine, and glycine. The advantages of one product do not individually inhibit the enzyme but the combination or accumulation of all end products has a strong inhibitory effect on glutamine synthesis. Glutamine synthase activity is also inhibited through adenilasi. The activity of adenylation is catalyzed by bifunctional adenylyltransferase/adenylyl removal (AT/AR). Glutamine and a regulating protein called PII act together to stimulate adenilasi.
The setting of proline biosynthesis may depend on the initial control measures through inhibition of negative feedback. In E. coli , prolet allosterically inhibits Glutamate 5-kinase which catalyzes the reaction of L-glutamate to L -? - Glutamyl phosphate unstable.
The synthesis of arginine also uses negative feedback as well as repression through repressor encoded by the argR gene. The gene products of argR , ArgR an aporepressor, and arginine as corepressor affect the operon of arginine biosynthesis. The degree of suppression is determined by the concentration of the repressor protein and the level of the corepressor.
Emanthrose 4-phosphate and phosphoenolpyruvate
Phenylalanine, tyrosine, and tryptophan are known as aromatic amino acids. The synthesis of the three shares the same beginning with their path; formation of chorismate from phosphoenolpyruvate (PEP) and erythrose 4- phosphate (E4P). The first step, condensing 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) of PEP/E4P, uses three isoenzymes AroF, AroG, and AroH. Each has a regulated synthesis of tyrosine, phenylalanine, and tryptophan, respectively. All of these isoenzymes have the ability to help regulate DAHP synthesis by inhibiting feedback methods. It acts in a cell by monitoring the concentrations of each of the three aromatic amino acids. When there is too much of one of them, that one will allosterically control the DAHP synthetase by "turn it off". With the first step of a deadly general pathway, the synthesis of the three amino acids can not be continued. The remainder of the enzyme in the general pathway (DAHP conversion to chorismate) appears to be constitutively synthesized, except for shikimic kinases which can be inhibited by shikimate by inhibition of the linear mixture type. If too much shikimate is produced then it can bind the shikimate kinase to stop production further.
In addition to the rules described above, any terminal amino acid path can be adjusted. This terminal line evolves from chorismate to the final product, either tyrosine, phenylalanine, or tryptophan. Each of these paths is arranged in the same way as the common path; with feedback inhibition at the first committed step of the path.
Tyrosine and phenylalanine share the same initial steps in their terminal path, chorismate is converted into a prephenate that is converted into a specific amino acid intermediate. This process is mediated by phenylalanine (PheA) or tyrosine (TyrA)-specific chorismate mutase-prephenate dehydrogenase. The reason for the specific enzyme of amino acids is because PheA uses simple dehydrogenase to convert prephenate to phenylpyruvate, while TyrA uses dehydrogenase which depends on NAD to make 4-hydroxylphenylpyruvate. Both PhaA and TyrA are feedbacks that are inhibited by each amino acid. Tyrosine may also be inhibited at the transcriptional level by TyrR repressor. TyrR binds the TyrR box to the operon near the gene promoter that it wants to suppress.
In the pathway-tryptophan synthesis path, the initial step converts chorismate to anthranilate using anthranilate synthase. This enzyme requires ammonia or glutamine as an amino group donor. The synthase of antranilates is governed by the trpE and trpG gene products. trpE encodes the first subunit, which binds chorismate and removes the amino group from donor to chorismate. trpG encodes a second subunit, which binds glutamine and uses it as an amino group donor so that the amine group can transfer to chorismate. The anthraicicate synthase is also regulated by feedback inhibition. The end product of tryptophan, having been produced in considerable quantities, is capable of acting as a co-repressor of TrpR repressor that represses the expression of the operon trp.
Oxonacetate/aspartate
The amino acid family of oxaloacetate/aspartate is composed of lysine, asparagine, methionine, threonine, and isoleucine. Aspartate may be converted into lysine, asparagine, methionine and threonine. Threonine also causes isoleucine. All these amino acids contain different mechanisms for their regulation, some more complex than others. All enzymes in this biosynthetic pathway are subject to regulation through inhibition of feedback and/or repression at the genetic level. As is typical in the highly branched metabolic pathway, there are additional regulations at each branch point of the path. This type of regulatory scheme allows control of the total flux of aspartate pathways in addition to the total flux of individual amino acids. The aspartate line uses L-aspartic acid as a precursor for the biosynthesis of a quarter of the amino acid building blocks. Without this pathway, protein synthesis would not be possible.
Aspartate
The aspartokinase enzyme, which catalyzes aspartate phosphorylation and initiates conversion into other amino acids, can be broken down into 3 isozymes, AK-I, II and III. AK-I is a feedback inhibited by threonine, whereas AK-II and III are inhibited by lysine. As a sidenote, AK-III catalyzes the phosphorylation of aspartic acid which is a commitment step in this biosynthetic pathway. The higher the concentration of threonine or lysine, the more aspartate kinase becomes down the regulation.
Lysine
Lysine is synthesized from aspartate through diaminopimelate pathway (DAP). The first two stages of the DAP pathway are catalyzed by aspartokinase and semialdehyde dehydrogenase aspartate and play a key role in lysine, threonine and methionine biosynthesis. There are two bifunctional, ThrA and MetL aspartokinase/homoserine dehydrogenases, in addition to monofunctional aspartokinase, LysC. The transcription of aspartokinase gene is regulated by later amino acid concentrations, lysine, threonine and methionine. The higher the amino acid concentration, the fewer the genes are transcribed. ThrA and LysC are also feedbacks that are inhibited by threonine and lysine. Finally, LysA decarboxylase DAP mediates the last step of lysine synthesis and is common for all bacterial species studied. The formation of aspartate kinase (AK), which catalyzes aspartate phosphorylation and initiates conversion into other amino acids, is also inhibited by both lysine and threonine, which prevent the formation of amino acids derived from aspartate. In addition, high lysine concentrations inhibit the activity of dihydrodipicolinate synthase (DHPS). Thus, in addition to inhibiting the first enzyme from the aspartate family biosynthetic pathway, lysine also inhibits the activity of the first enzyme after the branch point, which is the specific enzyme for lysine synthesis itself.
Asparagine
There are two different syntheses of asparagin found in bacterial species. Both of these synthetases, both of which are referred to as AsnC proteins, are encoded by two genes: AsnA and AsnB. AsnC is autogenously regulated, in which the product of a structural gene regulates the expression of the operon in which the gene resides. AsnC stimulation effects on AsnA transcription are decreased by asparagin. However, AsnC autoregulation is not affected by asparagin.
Methionine
Synthesis of methionine is under strict regulation. MetJ receptor proteins, in association with S-adenosyl-methionine corepressor protein, mediate the repression of methionine biosynthesis pathways. More recently, the new regulatory focus, MetR has been identified. The MetR protein is required for MetE and Meth gene expression and serves as a transcription transactivator for these genes. METR transcription activity is regulated by homocysteine, which is a metabolic metabolic precursor. It is also known that vitamin B12 can suppress the expression of the MetE gene, mediated by holoenzyme Meth.
Threonine
The threonine biosynthesis is regulated by allosteric regulation of its predecessor, homoserine, by altering the enzyme homoserin dehydrogenase structurally. This reaction occurs at the key branch point in the pathway, with the homoserine substrate serving as the precursor for lysine biosynthesis, methionine, threonine and isoleucine. High levels of threonine produce low homoserine synthesis levels. The synthesis of aspartate kinase (AK), which catalyzes aspartate phosphorylation and initiates conversion into other amino acids, is a feedback inhibited by lysine, isoleucine, and threonine, which prevents the synthesis of amino acids derived from aspartate. Thus, in addition to inhibiting the first enzyme from the aspartate family biosynthetic pathway, threonine also inhibits the activity of the first enzyme after the branch point, which is the specific enzyme for the synthesis of threonine itself.
Isoleucine
The threonine deaminase enzyme, dihydroxy acid dehydrase and transaminase are controlled by end product regulation. That is. The presence of isoleucine will lower the regulation of the formation of all three enzymes, thereby decreasing the regulation of threonin biosynthesis. High concentrations of isoleucine also result in decreased regulation of aspartate conversion into aspartyl-phosphate intermediates, thereby halting further biosynthesis of lysine, methionine, threonine, and isoleucine.
Ribose 5-phosphate
The histidine synthesis in E. coli is a complex pathway involving 10 reactions and 10 enzymes. Synthesis begins with 5-phosforibosil-pyrophosphate (PRPP) and ends with histidine and occurs by the following enzyme reactions:
HisG- & gt; HisE/HisI- & gt; HisA- & gt; HisH- & gt; HisF- & gt; HisB- & gt; HisC- & gt; HisB- & gt; HisD (HisE/I dan HisB keduanya adalah enzim bifunctional)
All enzymes are encoded on the operon. These operons have different blocks of the leader sequence, called blocks 1:
Met-Thr-Arg-Val-Gln-Phe-Lys-His-His-His-His-His-His-His-His-Pro-Asp
This leader sequence is essential for setting histidine in "E. coli". The operon operates under a coordinated regulatory system in which all gene products are pressed or pressed together. A major factor in histidine synthesis or derepression is the concentration of histidine-loaded tRNAs. The histidine setting is actually quite simple given the complexity of its biosynthetic pathway, and closely resembles the regulation of tryptophan. In this system the full leader order has 4 complementary strand blocks that can form a hairpin loop structure. Block one, shown above, is the key to regulation. When histidine is charged a low level tRNA inside a ribosome cell will stretch on its residual straps in block 1. This ribosomal stalling will allow complementary strands 2 and 3 to form a hairpin loop. The loop formed by strands 2 and 3 forms the anti-terminator and the translation of its gene will continue and histidine will be generated. However, when histidine charges a high tRNA level the ribosome will not stop in block 1, this will not allow the 2nd and 3rd strands to form the hairpin. Instead of strands 3 and 4 will form a hairpin loop farther downstream of the ribosome. The hairpin loop formed by strands 3 and 4 is a termination loop, when the ribosome comes into contact with the loop, it will "cripple" the transcript. When the ribosome is removed its gene will not be translated and histidine will not be produced by the cell.
3-Phosphoglycerate
Serine
Serine is the first amino acid in this family to be produced; then modified to produce both glycine and cysteine ​​(and many other biologically important molecules). Serine is formed from 3-phosphoglycerate in the following pathway:
3-phosphoglycerate- & gt; phosphohydroxyl-pyruvate- & gt; fosfoserin - & gt; serin
The conversion of 3-phosphoglycerate to phosphohydroxyl-pyruvate is achieved by dehydrogenase of the phosphoglycerate enzyme. This enzyme is a key regulatory step in this pathway. Phosphoglyceric dehydrogenase is regulated by serine concentrations in cells. At high concentrations, this enzyme will become inactive and serine will not be produced. At low serine concentrations, the enzyme will be fully active and serine will be produced by bacteria. Since serine is the first amino acid produced in this family, both glycine and cysteine ​​will be regulated by serine concentrations available in the cell.
Glycine
Glycine is synthesized from serine using serine hydromethyltransferase (SHMT) enzyme, which is encoded by the glyA gene. The enzyme effectively removes the hydroxyl group from the serine and replaces it with the methyl group to produce glycine. This reaction is the only way E. coli can produce glycine. The glyA setting is very complex and is known to include serine, glycine, methionine, purine, thymine, and folate, but the complete mechanism is unexplained. Methionine gene products Metr and homocysteine ​​â € <â € Cysteine ​​
Cysteine ​​is a very important molecule for bacterial survival. These amino acids store sulfur atoms and can actively participate in the formation of disulphide bonds. The genes needed for cysteine ​​synthesis are encoded on the cys regulator. The integration of sulfur into the molecule is regulated positively by CysB. CysB is the main focus of cysteine ​​regulation. The effective inducer of this regulon is N-acetyl-serine (NAS) and a very small amount of reduced sulfur. Function CysB by binding to half the DNA site on the cys regulon. Half of these sites differ in numbers and settings depending on the desired promoter. But there are one and a half sites that are conserved. It lies only in the upstream of the promoter -35 sites. There are also several accessory sites depending on the promoter. In the absence of an inducer, NAS, CysB will bind the DNA and include many of the half-sections of the accessory. Without half-site accessories, regulon can not be transcribed and cysteine ​​will not be produced. It is believed that the presence of NAS causes CysB to undergo conformational changes. This conformational change allows CysB to bind correctly to all half the sites and cause the recruitment of RNA polymerases. RNA polymerase will transcribe cys regulon and cysteine ​​to be produced.
Further regulations are required for this path, however. CysB can actually manage its own transcription by binding to its own DNA sequence and blocking RNA polymerases. In this case the NAS will act to ban CysB binding to its own DNA sequence. OAS is a precursor of NAS, cysteine ​​itself can inhibit CysE that serves to create OAS. Without the required OAS, NAS will not be produced and cysteine ​​will not be produced. There are two other negative cysteine ​​regulators. These are molecular sulfides and thiosulfates, they act to bind to CysB and they compete with NAS for CysB binding.
Piruvat
Pyruvate is the end result of glycolysis and can be incorporated into the TCA cycle and fermentation process. The reaction that begins with one or two pyruvate molecules causes the synthesis of alanine, valine, and leucine. Inhibition of feedback from the final product is the main method of inhibition, and, in E. coli , operon ilvEDA also plays a role in this rule.
Alanine
Alanine is produced by transamination of one molecule of pyruvate using two alternative steps: 1) the conversion of glutamate into? -ketoglutarate using glutamate-alanine transaminase, and 2) valine conversion to? -ketoisovalerate via Transaminase C.
Not much is known about the alanine synthesis setting. The only definite method is the ability of bacteria to suppress transaminase activity C either valine or leucine (see ilvEDA operon ). In addition, alanine biosynthesis does not seem to be regulated.
Valine
Valine is produced by a pathway of four enzymes. Beginning with the reaction of two pyruvate molecules catalyzed by acetohydroxy acetic acid that produces? -acetolactate. The second step is NADPH H - depends on the reduction? -acetolactate and migration of methane groups to produce?,? -dihydroxyisovalerate. This is catalyzed by Acetohydroxy isomeroreductase. The third reaction is dehydration reaction?,? -dihydroxyisovalerate catalyzed by dehydration of Dihydroxy acid so as to produce? -ketoisovalerate. Finally, transamination is catalyzed either by alanine-valine transaminase or transaminase-glutamate-valine in valine.
Valine inhibits feedback to inhibit the synthase of acetic acid used to combine the first two pyruvate molecules.
Leucine
The leucine synthesis pathway deviates from the valine path starting with? -ketoisovalerate. ? -Isopropylmalate synthase reacts with this substrate and Acetyl CoA to produce? -isopropylmalate. Isomerase then isomerizes? -isopropylmalate becomes? -isopropylmalate. The third step is NAD-dependent oxidation -isopropylmalate through the action of dehydrogenase to produce? -ketoisokaproat. Finally it is transamination through the action of glutamate-leucine transaminase to produce leucine.
Leusin, like valine, set the first step of its path by blocking action? -sopropylmalate synthase. Since leucine is synthesized by diversion from the valine synthetic pathway, inhibition of valine feedback in its path may also inhibit leucine synthesis.
ilvEDA operon
The genes that encode the dihydroxy acid dehydrase used in the manufacture? -ketoisovalerate and Transaminase E, as well as other enzymes encoded on the operand ilvEDA. This operon is bonded and inactivated by valine, leucine, and isoleucine. (Isoleucine is not a direct derivative of pyruvate, but is produced by the use of many of the same enzymes used to produce valine and, indirectly, leucine.) When one of these amino acids is limited, the farthest gene from the amino acid This operon binding site may be transcribed. When these two amino acids are limited, the next closest genes to the binding site can be transcribed, and so on.
Amino acids as precursors for other biomolecules
Amino acids are precursors of various biomolecules. Glutathione (? -Glu-Cys-Gly) serves as a sulfhydryl buffer and detoxifying agent. Glutathione peroxidase, selenoenzyme, catalyzes the reduction of hydrogen peroxide and organic peroxide by glutathione. Nitric oxide, a short-lived courier, is formed from arginine. Porphyrins are synthesized from glycine and succinyl CoA, which condenses to give? -aminolevulinate. These two intermediate molecules become related to the shape of porphobilinogen. Four molecules of porphobilinogen combine to form a linear tetrapyrrole, which is cyclized to uroporphyrinogen III. Oxidation and side chain modifications lead to the synthesis of protoporfirin IX, which acquires the iron atoms to form heme.
References
External links
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