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Chapter 22 Biosynthesis of Amino Acids Nucleotides and Related Molecules 22 1 Overview of Nitrogen Metabolism The Nitrogen Cycle Maintains a Pool of Biologically Available Nitrogen The most important source of nitrogen is air o Relatively few species can convert atmospheric nitrogen into a useful form Nitrogen cycle available nitrogen o Fixation bacteria to yield ammonia o Nitrification nitrate a vast set of processes that salvage and reuse biologically reduction of atmospheric nitrogen by nitrogen fixing most ammonia that reaches the soil is oxidized to o Plants and bacteria reduce the nitrate and nitrite through nitrate and nitrite reductases forming ammonia o Animals use plants as a source of amino acids o When organisms die microbial degradation of their proteins returns o Denitrification ammonia to the soil conditions by bacteria conversion of nitrate to N2 under anaerobic Anammox These bacteria use this process to generate ATP anaerobic ammonia oxidation o Converting ammonia and nitrite to N2 Nitrogen Is Fixed by Enzymes of the Nitrogenase Complex Only certain bacteria and archaea can fix atmospheric nitrogen o Cyanobacteria of soils and fresh and salt waters o Methanogenic archaea strict anaerobes that obtain energy and carbon by converting H2 and CO2 to methane o Other kinds of free living soil bacteria o Symbionts in the root nodules of leguminous plants The first important product of nitrogen fixation is ammonia produced in an exergonic reaction N2 Nitrogen fixation has a really high activation energy due to the triple bond in o Overcome by the binding and hydrolysis of ATP a highly conserved complex of proteins that carries Nitrogenase complex out biological nitrogen fixation o Dinitrogenase reductase contains a single 4Fe 4S redox center bound between the subunits and can be oxidized and reduced by one electron a dimer of two identical subunits that 2 binding sites for ATP ADP o Dinitrogenase that contains iron and molybdenum a tetramer with two copies of two different subunits Redox centers have 2 Mo 32 Fe and 30 S per tetramer P clusters Nitrogen fixation is carried out by a highly reduced form of dinitrogenase and requires eight elections o Six electrons to reduce N2 o Two electrons to produce H2 o Dinitrogenase is reduced by the transfer of electrons from dinitrogenase reductase one at a time o Each turn of the cycle requires 2 ATP o Ferredoxin dinitrogenase reductase Dinitrogenase reductase is inactivated in air reduced flavodoxin and other sources reduce o Some nitrogen fixing bacteria live anaerobically or repress nitrogenase synthesis when in air o Some aerobic species uncouple electron transfer from ATP synthesis o Symbionts in root nodules of leguminous plants have both energy requirements and oxygen lability taken care of Leghemoglobin bacteria in root nodules to protect them from oxygen an oxygen binding heme protein that bathes Ammonia Is Incorporated into Biomolecules through Glutamate and Glutamine Glutamate acids and other nitrogen containing biomolecules and glutamine provide the entry point for ammonia into amino o Glutamate is the source of amino groups for most other amino acids o Glutamine is the source of amino groups in a wide range of The most important pathway for the assimilation of NH4 into glutamate catalyzes the reaction of glutamate and NH4 to biosynthetic processes requires two reactions o Glutamine synthetase yield glutamine Two steps o Glutamate synthetase from glutamine in plants and bacteria catalyzes a reaction that produces glutamate Glutamate can also be formed by reaction of ketoglutarate and NH4 catalyzed by L glutamate dehydrogenase o Uses NADPH o L glutamate dehydrogenase is located in the mitochondrial matrix in eukaryotes Glutamine Synthetase Is a Primary Regulatory Point in Nitrogen Metabolism Glutamine synthetase is regulated allosterically and by covalent modification o Alanine glycine and at least six end products of glutamine metabolism are allosteric inhibitors o Covalent modification by adenylation addition of AMP which increases the sensitivity to allosteric inhibitors Adenylyltransferase promotes adenylylation and deadenylylation o Activity is modulated by binding to a regulatory protein called PII which is regulated by covalent modification uridylylation Uridylylated PII stimulates deadenylylation Deuridylylatd PII stimulates adenylylation Uridylyltransferase uridylylates and deuridylylates PII Inhibited by binding of glutamine and Pi to uridylyltransferase Stimulated by binding of ketoglutarate and ATP to PII o PII also regulates the activation of transcription of the gene encoding glutamine synthetase Deuridylylated PII decreases transcription When glutamine levels are high glutamine synthetase activity decreases When glutamine levels are low and ketoglutarate and ATP are available glutamine synthesis increases Multiple layers of regulation increase sensitivity Several Classes of Reactions Play Special Roles in the Biosynthesis of Amino Acids and Nucleotides Chemical rearrangements o Transamination reactions and other rearrangements promoted by enzymes containing pyridoxal phosphate o Transfer of one carbon groups with either tetrahydrofolate or S adenosylmethionine as cofactor o Transfer of amino groups derived from the amide nitrogen of glutamine Glutamine amidotransferases transfers o All have two structural domains the enzymes catalyzing amino group One binding glutamine One binding the second substrate which serves as amino group acceptor 22 2 Biosynthesis of Amino Acids Nonessential amino acids Essential amino acids 5 phosphoribosyl 1 pyrophosphate pathways of amino acid and nucleotide synthesis o Synthesized from ribose 5 posphate amino acids that are not needed in the diet amino acids that must be obtained from food PRPP an intermediate in several Catalyzed by ribose phosphate pyrophosphokinase Ketoglutarate Gives Rise to Glutamate Glutamine Proline and Arginine a cyclized derivative of glutamate synthesized from glutamate via ornithine and the urea cycle in Proline Arginine animals Arginase converts arginine to ornithine and urea and the ornithine is converted to glutamate semialdehyde by ornithine aminotransferase Serine Glycine and Cysteine Are Derived from 3 Phosphoglycerate an amino acid whose synthetic pathway is the same in all organisms Serine In the first step of serine formation the hydroxyl group of 3 phosphoglycerate is oxidized by a dehydrogenase using NAD to yield 3 phosphohydroxypyruvate

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MSU BMB 462 - Chapter 22 – Biosynthesis of Amino Acids

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