The Biosynthesis of Amino Acids

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The assembly of biological molecules, including proteins and nucleic acids, requires the generation of appropriate starting materials. We have already considered the assembly of carbohydrates in discussions of the Calvin cycle and the pentose phosphate pathway (Chapter 20). The present chapter and the next two examine the assembly of the other important building blocks—namely, amino acids, nucleotides, and lipids.

The pathways for the biosynthesis of these molecules are extremely ancient, going back to the last common ancestor of all living things. Indeed, these pathways probably predate many of the pathways of energy transduction discussed in Part II and may have provided key selective advantages in early evolution. Many of the intermediates in energy-yielding pathways play a role in biosynthesis as well. These common intermediates allow efficient interplay between energy-yielding (catabolic) and energy-requiring biosynthetic (anabolic) pathways. Thus, cells are able to balance the degradation of compounds for energy mobilization and the synthesis of starting materials for macromolecular construction.

We begin our consideration of biosynthesis with amino acids—the building blocks of proteins and the nitrogen source for many other important molecules, including nucleotides, neurotransmitters, and prosthetic groups such as porphyrins. Amino acid biosynthesis is intimately connected with nutrition because many higher organisms, including human beings, have lost the ability to synthesize some amino acids and must therefore obtain adequate quantities of these essential amino acids in their diets. Furthermore, because some amino acid biosynthetic enzymes are absent in mammals but present in plants and microorganisms, they are useful targets for herbicides and antibiotics.

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Nitrogen is an essential component of amino acids. Earth has an abundant supply of nitrogen, but it is primarily in the form of atmospheric nitrogen gas (N₂), a remarkably inert molecule. Thus, a fundamental problem for biological systems is to obtain nitrogen in a more usable form. This problem is solved by certain microorganisms capable of reducing the inert N ≡ N molecule of nitrogen gas to two molecules of ammonia in one of the most amazing reactions in biochemistry. Nitrogen in the form of ammonia is the source of nitrogen for all the amino acids. The carbon backbones come from the glycolytic pathway, the pentose phosphate pathway, or the citric acid cycle.

In amino acid production, we encounter an important problem in biosynthesis—namely, stereochemical control. Because all amino acids except glycine are chiral, biosynthetic pathways must generate the correct isomer with high fidelity. In each of the 19 pathways for the generation of chiral amino acids, the stereochemistry at the α-carbon atom is established by a transamination reaction that includes pyridoxal phosphate (PLP). Almost all the aminotransferases that catalyze these reactions descend from a common ancestor, illustrating once again that effective solutions to biochemical problems are retained throughout evolution.

Biosynthetic pathways are often highly regulated such that building blocks are synthesized only when supplies are low. Very often, a high concentration of the final product of a pathway inhibits the activity of allosteric enzymes that function early in the pathway to control the committed step. These enzymes are similar in functional properties to aspartate transcar-bamoylase and its regulators (Section 10.1). Feedback and allosteric mechanisms ensure that all 20 amino acids are maintained in sufficient amounts for protein synthesis and other processes.