Chapter 22 Biosynthesis of Amino Acids, Nucleotides, and Related Molecules

The first intermediate with a complete purine ring is inosinate (IMP).

As in the tryptophan and histidine biosynthetic pathways, the enzymes of IMP synthesis appear to be organized as large, multienzyme complexes in the cell. Once again, evidence comes from the existence of single polypeptides with several functions, some catalyzing nonsequential steps in the pathway. In eukaryotic cells ranging from yeast to fruit flies to chickens, steps <1, (3), and © in Figure 22-33 are catalyzed by a multifunctional protein. An additional multifunctional protein catalyzes steps 10 and (11). In humans, a multifunctional enzyme combines the activities of AIR carboxylase and SAICAR synthetase (steps (S^and (8)). In bacteria, these activities are found on separate proteins, but a large noncovalent complex may exist in these cells. The channeling of reaction intermediates from one enzyme to the next permitted by these complexes is probably especially important for unstable intermediates such as 5-phosphoribosylamine.

Conversion of inosinate to adenylate requires the insertion of an amino group derived from aspartate (Fig. 22-34); this takes place in two reactions similar to those used to introduce N-1 of the purine ring (Fig. 22-33, steps @ and (9)). A crucial difference is that GTP rather than ATP is the source of the high-energy phosphate in synthesizing adenylosuccinate. Guanylate is formed by the NAD+-requiring oxidation of inosinate at C-2, followed by addition of an amino group derived from glu-tamine. ATP is cleaved to AMP and PPj in the final step (Fig. 22-34).

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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