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966 Chapter 25 DNA Metabolism

Many DNA viruses encode their own DNA poly-merases, and some of these have become targets for pharmaceuticals. For example, the DNA polymerase of the herpes simplex virus is inhibited by acyclovir, a compound developed by Gertrude Elion (p. 876). Acyclovir consists of guanine attached to an incomplete ribose ring. It is phosphorylated by a virally encoded thymi-dine kinase; acyclovir binds to this viral enzyme with an affinity 200-fold greater than its binding to the cellular thymidine kinase. This ensures that phosphorylation occurs mainly in virus-infected cells. Cellular kinases convert the resulting acyclo-GMP to acyclo-GTP, which is both an inhibitor and a substrate of DNA polymerases, and which competitively inhibits the herpes DNA poly-merase more strongly than cellular DNA polymerases. Because it lacks a 3' hydroxyl, acyclo-GTP also acts as a chain terminator when incorporated into DNA. Thus viral replication is inhibited at several steps.

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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