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Serotonin

Serotonin

Polyamines such as spermine and spermidine, involved in DNA packaging, are derived from methionine and ornithine by the pathway shown in Figure 22-30. The first step is decarboxylation of ornithine, a precursor of arginine (Fig. 22-10). Ornithine decarboxylase, a PLP-requiring enzyme, is the target of several powerful inhibitors used as pharmaceutical agents (Box 22-2). ■

Arginine Is the Precursor for Biological Synthesis of Nitric Oxide

A surprise finding in the mid-1980s was the role of nitric oxide (NO)—previously known mainly as a component of smog—as an important biological messenger.

FIGURE 22-29 Biosynthesis of some neurotransmitters from amino acids. The key step is the same in each case: a PLP-dependent decarboxylation (shaded in pink).

This simple gaseous substance diffuses readily through membranes, although its high reactivity limits its range of diffusion to about a 1 mm radius from the site of synthesis. In humans NO plays a role in a range of physiological processes, including neurotransmission, blood clotting, and the control of blood pressure. Its mode of action is described in Chapter 12 (p. 434).

Nitric oxide is synthesized from arginine in an NADPH-dependent reaction catalyzed by nitric oxide synthase (Fig. 22-31), a dimeric enzyme structurally related to NADPH cytochrome P-450 reductase (see Box 21-1). The reaction is a five-electron oxidation. Each subunit of the enzyme contains one bound molecule of each of four different cofactors: FMN, FAD, tetrahydrobiopterin, and Fe3+ heme. NO is an unstable molecule and cannot be stored. Its synthesis is stimulated by interaction of nitric oxide synthase with Ca2+-calmodulin (see Fig. 12-21).

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