The review deals with synthesis and reactions of quinoxaline derivatives as well as their diverse pharmacological and biological properties. Quinoxalines and fused ring systems show diverse pharmacological activities. Syntheses of quinoxaline derivatives many different methods of synthetic strategies have been presented.
In most cases bacteria would rather use amino acids in their environment than make them from scratch. It takes a considerable amount of energy to make the enzymes for the pathway as well as the energy required to drive some of the reactions of amino acid biosynthesis. The genes that code for amino acid synthesis enzymes and the enzymes themselves are under tight control and are only turned on when they are needed.
Trytophan synthesis is complex and involves 5 steps from chorismate. Glutamate donates an amine group in the first step of the pathway and pyruvate is lost from chorismate. In the next threes steps a ribose sugar is added, this eventually contributes to the 5 membered ring of tryptophan. Energy is contributed to the process in the form of hydrolysis of pyrophosphate. This hydrolysis helps drive the addition of the ribose sugar in the second step of the reaction. In the last step of the pathway serine serves as the donor of the carbon amino group of tryptophan.
The synthesis of tyrosine is very similar to the synthesis of phenylalanine, but the reactions are carried out by different enzymes under different regulatory control. NADH is created in the formation of 4-hydroxyphenylpyruvate. Tyrosine is made by a similar transamination reaction as that seen in phenylalanine synthesis.
Chorismate is converted to phenylpyruvate in two steps and phenylalanine is synthesized by a transamination reaction with glutamate. No energy is require to run these reactions.
The synthesis of lysine has been found to consist of different reactions in different bacterial species. A somewhat generalize pathway is presented. Lysine synthesis involves the addition of pyruvate to aspartate semialdehyde, the use of a CoA intermediate (either acetyl CoA or succinyl-CoA) and the addition of an amino group from glutamate. The group added from CoA (either succinyl or acetyl) serves as a blocking group, protecting the amino group from attack during transamination by glutamate. NADPH + H+ is required for reduction in the second step of the pathway.
Alanine synthesisis is a bit of a mystery. Several reactions have been identified, but it has been impossible to generate an alanine and therefore positively identify a required pathway. There are several pathways and the most likely is formation of alanine by transamination from glutamate onto pyruvate. A transamination using valine instead of glutamate is also possible.
Figure 4 - Formation of asparagine. Notice the use of AMP instead of ADP in this reaction. This releases more energy which is needed to drive the synthesis.
The biosynthesis of serine and glycine constitute a major metabolic pathway that plays a central role in the formation of other amino acids, nucleic acids and phospholipids. When is grown on glucose, fully 15% of carbon assimilated passes through the serine pathway. Synthesis of serine and glycine starts with oxidation of 3-phosphoglycerate forming 3-phosphohydroxy pyruvate and NADH. A transamination reaction with glutamate forms 3-phosphoserine and removal of the phosphate yields serine. Glycine is generated by removal of the methyl group from serine. Energy is not required for this pathway, in fact it yields energy in the form of reduced NADH.
The rest of the simple reactions involve transfer of the amino group (transamination) from glutamate or glutamine to a central metabolite to make the required amino acid. Aspartate is synthesize by the transfer of a ammonia group from glutamate to oxaloacetate.
In most cases these amino acids can be synthesize by one step reactions from central metabolites. They are simple in structure and their synthesis is also straight forward.
Synthesis of cysteine is a two step reaction. Serine and acetyl-CoA combine to form -acetylserine. Sulfide from is then added to -acetylserine to form cysteine. The pathway for cysteine synthesis was covered in .
The amino acids synthesis pathways can be grouped into several logical units. These units reflect either common mechanisms or the use of common enzymes that synthesize more than one amino acid. These categories are: simple reactions, branch chain amino acids, aromatic amino acids, threonine/lysine, serine/glycine, and unique pathways. The aromatic amino acids, threonine/lysine and serine/glycine pathways have a common beginning and then diverge to form the amino acid of interest.
The synthesis of histidine is long and complex and its pathway is intertwined with nucleic acid biosynthesis (specifically purine). The pathway seems to be universal in all organisms able to synthesize histidine. The first five steps of the pathway take ribose from phosphoribosyl pyrophosphate (PRPP) and transform it into Imadiazoleglycerol phosphate. Once the imadiazole ring is formed, glutamate donates the -amino group and the newly formed amine is oxidized to histidine in the last step of the pathway. Energy is required in the form of ATP (in this case elements of the ATP molecule actually becomes part of the amino acid) and pyrophosphate which is lost from phosphoribosyl pyrophosphate and ATP help drive the reaction.