Chapter 22 BIOSYNTHESIS OF AMINO ACIDS, NUCLEOTIDES, AND RELATED MOLECULES
Nitrogen ranks behind only carbon, hydrogen, and oxygen in its contribution to the mass of living systems. Most of this nitrogen is bound up in amino acids and nucleotides. In this chapter we address all aspects of the metabolism of these nitrogen-containing compounds except amino acid catabolism, which is the subject of Chapter 18.
In this final chapter covering anabolic processes, some of the underlying principles are unique, while others will be familiar from Chapter 21 and the consideration of gluconeogenesis in Chapter 14:
Amino acids and nucleotides are the precursors to proteins and nucleic acids, respectively. They also give rise to numerous neurotransmitters, metabolic cofactors, and other molecules of biological importance.
The supply of biologically available nitrogen can be limiting in many environments. Atmospheric is relatively inert and must be converted to other forms, such as ammonia and nitrate, to accommodate the requirements of life. A complex web of enzymatic processes, based primarily in microorganisms, interconverts the various molecular forms that comprise the global inventory of reactive nitrogen.
Oxygen and nitrogen metabolism are interlinked. The oxidation and reduction of the various forms of nitrogen in the biosphere often involve oxygen.
Regulation again plays an important role. Many of the processes covered in this chapter are regulated to carefully conserve a critical and limited resource. Tight regulation is needed to maintain balanced supplies of amino acids and nucleotides. The metabolic flux through most of these pathways is far less than for carbohydrate or lipid biosynthetic pathways; most amino acids and nucleotides are not stored, but are synthesized as they are needed.
The amino acids glutamate and glutamine represent the entry point where reactive forms of nitrogen are incorporated into biological systems. Reflecting their importance, the concentrations of these amino acids are sufficiently elevated in many tissues that they are major contributors to the electrochemical environment of cells. The prominent role of these two amino acids is a universal feature of animate nitrogen metabolism, yet another molecular manifestation of the shared evolutionary history of all organisms on the planet.
Like other anabolic pathways, the reaction sequences in amino acid and nucleotide biosynthesis are endergonic and reductive. They use ATP as a source of metabolic energy and they use a reduced electron carrier (usually NADPH) as a reductant.
Amino acids and nucleotides are the precursors to proteins and nucleic acids, respectively. They also give rise to numerous neurotransmitters, metabolic cofactors, and other molecules of biological importance.
The supply of biologically available nitrogen can be limiting in many environments. Atmospheric is relatively inert and must be converted to other forms, such as ammonia and nitrate, to accommodate the requirements of life. A complex web of enzymatic processes, based primarily in microorganisms, interconverts the various molecular forms that comprise the global inventory of reactive nitrogen.
Oxygen and nitrogen metabolism are interlinked. The oxidation and reduction of the various forms of nitrogen in the biosphere often involve oxygen.
Regulation again plays an important role. Many of the processes covered in this chapter are regulated to carefully conserve a critical and limited resource. Tight regulation is needed to maintain balanced supplies of amino acids and nucleotides. The metabolic flux through most of these pathways is far less than for carbohydrate or lipid biosynthetic pathways; most amino acids and nucleotides are not stored, but are synthesized as they are needed.
The amino acids glutamate and glutamine represent the entry point where reactive forms of nitrogen are incorporated into biological systems. Reflecting their importance, the concentrations of these amino acids are sufficiently elevated in many tissues that they are major contributors to the electrochemical environment of cells. The prominent role of these two amino acids is a universal feature of animate nitrogen metabolism, yet another molecular manifestation of the shared evolutionary history of all organisms on the planet.
Like other anabolic pathways, the reaction sequences in amino acid and nucleotide biosynthesis are endergonic and reductive. They use ATP as a source of metabolic energy and they use a reduced electron carrier (usually NADPH) as a reductant.Discussing the biosynthetic pathways for amino acids and nucleotides together is a sound approach, not only because both classes of molecules contain nitrogen, but also because the two sets of pathways are extensively intertwined, with several key intermediates in common. Certain amino acids or parts of amino acids are incorporated into the structure of purines and pyrimidines, and in one case, part of a purine ring is incorporated into an amino acid (histidine). The two sets of pathways also share much common chemistry, in particular a preponderance of reactions involving the transfer of nitrogen or one-carbon groups.
The sheer number of steps and variety of intermediates in the pathways described here can be intimidating to the beginning biochemistry student. These pathways are best approached by maintaining a focus on metabolic principles we have already discussed, on key intermediates and precursors, and on common classes of reactions. Even a cursory look at the chemistry can be rewarding, for some of the most unusual chemical transformations in biological systems occur in these pathways; for instance, we find prominent examples of the rare biological use of the metals molybdenum, selenium, and vanadium. The effort also offers a practical dividend, especially for students of human or veterinary medicine. Many genetic diseases of humans and animals have been traced to an absence of one or more enzymes of amino acid and nucleotide metabolism, and many pharmaceuticals in common use to combat infectious diseases are inhibitors of enzymes in these pathways — as are a number of the most important agents in cancer chemotherapy.