Amino acid synthesis
Amino acid synthesis is the set of biochemical processes (metabolic pathways) by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids). α-Ketoglutarates: glutamate, glutamine, proline, arginine Most amino acids are synthesized from α-ketoacids, and later transaminated from another amino acid, usually glutamate. The enzyme involved in this reaction is an aminotransferase. α-ketoacid + glutamate ⇄ amino acid + α-ketoglutarate Glutamate itself is formed by amination of α-ketoglutarate: α-ketoglutarate + ⇄ glutamate The α-ketoglutarate family of amino acid synthesis (synthesis of glutamate, glutamine, proline and arginine) begins with α-ketoglutarate, an intermediate in the Citric Acid Cycle. The concentration of α-ketoglutarate is dependent on the activity and metabolism within the cell along with the regulation of enzymatic activity. In E. coli citrate synthase, the enzyme involved in the condensation reaction initiating the Citric Acid Cycle is strongly inhibited by α-ketoglutarate feedback inhibition and can be inhibited by DPNH as well high concentrations of ATP. This is one of the initial regulations of the α-ketoglutarate family of amino acid synthesis. The regulation of the synthesis of glutamate from α-ketoglutarate is subject to regulatory control of the Citric Acid Cycle as well as mass action dependent on the concentrations of reactants involved due to the reversible nature of the transamination and glutamate dehydrogenase reactions. The conversion of glutamate to glutamine is regulated by glutamine synthetase (GS) and is a key step in nitrogen metabolism. This enzyme is regulated by at least four different mechanisms: 1. Repression and depression due to nitrogen levels; 2. Activation and inactivation due to enzymatic forms (taut and relaxed); 3. Cumulative feedback inhibition through end product metabolites; and 4. Alterations of the enzyme due to adenylation and deadenylation. In rich nitrogenous media or growth conditions containing high quantities of ammonia there is a low level of GS, whereas in limiting quantities of ammonia the specific activity of the enzyme is 20-fold higher. The confirmation of the enzyme plays a role in regulation depending on if GS is in the taut or relaxed form. The taut form of GS is fully active but, the removal of manganese converts the enzyme to the relaxed state. The specific conformational state occurs based on the binding of specific divalent cations and is also related to adenylation. The feedback inhibition of GS is due to a cumulative feedback due to several metabolites including L-tryptophan, L-histidine, AMP, CTP, glucosamine-6-phosphate and carbamyl phosphate, alanine, and glycine. An excess of any one product does not individually inhibit the enzyme but a combination or accumulation of all the end products have a strong inhibitory effect on the synthesis of glutamine. Glutamine synthase activity is also inhibited via adenylation. The adenylation activity is catalyzed by the bifunctional adenylyltransferase/adenylyl removal (AT/AR) enzyme. Glutamine and a regulatory protein called PII