Biosynthesis Of Amino Acids Nucleotides And Related Molecules

22.1 Overview of Nitrogen Metabolism 834

22.2 Biosynthesis of Amino Acids 841

22.3 Molecules Derived from Amino Acids 854

22.4 Biosynthesis and Degradation of Nucleotides 862

Time passes rapidly when you are having fun. The thrill of seeing people get well who might otherwise have died of disease ... cannot be described in words. The Nobel Prize was only the icing on the cake.

—Gertrude Elion, quoted in an article in Science, 2002

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 covered in Chapter 18.

Discussing the biosynthetic pathways for amino acids and nucleotides together is a sound approach, not only because both classes of molecules contain nitrogen (which arises from common biological sources) but 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 pathways described here can be intimidating to the beginning biochemistry student. Their complexity arises not so much from the chemistry itself, which in many cases is well understood, but from the sheer number of steps and variety of intermediates. 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.

Regulation is crucial in the biosynthesis of the nitrogen-containing compounds. Because each amino acid and each nucleotide is required in relatively small amounts, the metabolic flow through most of these pathways is not nearly as great as the biosynthetic flow leading to carbohydrate or fat in animal tissues. Because the different amino acids and nucleotides must be made in

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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