Biosynthesis of Amino Acids:-Three Nonessential and Six Essential Amino Acids Are Synthesized from Oxaloacetate and Pyruvate
Alanine and aspartate are synthesized from pyruvate and oxaloacetate, respectively, by transamination from glutamate. Asparagine is synthesized by amidation of aspartate, with glutamine donating the NH4. These are nonessential amino acids, and their simple biosynthetic pathways occur in all organisms. Methionine, threonine, lysine, isoleucine, valine, and leucine are essential amino acids. Their biosynthetic pathways are complex and interconnected (Fig. 1).
FIGURE 1 Biosynthesis of six essential amino acids from oxalo acetate and pyruvate in bacteria: methionine, threonine, lysine, iso leucine, valine, and leucine. Here, and in other multistep pathways, the enzymes are listed in the key. Note that L,L-α,-ε diaminopimelate, the product of step14, is symmetric. The carbons derived from pyruvate (and the amino group derived from glutamate) are not traced beyond this point, because subsequent reactions may place them at either end of the lysine molecule.
In some cases, the pathways in bacteria, fungi, and plants differ significantly. The bacterial pathways are outlined in Figure 1. Aspartate gives rise to methionine, threonine, and lysine. Branch points occur at aspartate -semi aldehyde, an intermediate in all three pathways, and at homoserine, a precursor of threonine and methionine. Threonine, in turn, is one of the precursors of isoleucine. The valine and isoleucine pathways share four en zymes (Fig. 1, steps 18 to 21). Pyruvate gives rise to valine and isoleucine in pathways that begin with condensation of two carbons of pyruvate (in the form of hydroxyethyl thiamine pyrophosphate) with another molecule of pyruvate (valine path) or with-ketobutyrate (isoleucine path). The -ketobutyrate is derived from threonine in a reaction that requires pyridoxal phosphate (Fig. 1, step 17). An intermedi ate in the valine pathway, -Ket isovalerate, is the starting point for a four-step branch pathway leading to leucine (steps 22 to 25).
FIGURE 2 Biosynthesis of chorismate, an intermediate in the synthesis of aromatic amino acids in bacteria and plants. All carbons are derived from either erythrose 4-phosphate (light purple) or phosphoenolpyruvate (pink). Note that the NAD required as a cofactor in step 2 is released unchanged; it may be transiently reduced to NADH during the reaction, with formation of an oxidized reaction intermediate. Step 6 is competitively inhibited by glyphosate (-COO-CH2 -NH-CH2 -PO32-), the active ingredient in the widely used herbicide Roundup. The herbicide is relatively nontoxic to mammals, which lack this biosynthetic pathway. The chemical names quinate, shikimate, and chorismate are derived from the names of plants in which these intermediates have been found to accumulate.
