Fundamentals of Biochemistry Third Edition Donald Voet • Judith G. Voet • Charlotte W. Pratt Chapter 13 Biochemical Signaling Copyright © 2008 by John Wiley & Sons, Inc.

There are many forms that biochemicals are used to signal systems to start or stop functioning. An obvious example are the class of compounds called hormones, produced by endocrine glands.

For instance, the adrenal medulla synthesizes catecholamines, one of which is norepinephrine, which is methylated to become epinephrine These chemicals enter the bloodstream and interact with cells that have α and β adrenergic receptors in their membranes. These chemicals can act as agonists or antagonists.

Protein tyrosine kinases (PTKs) are a class of enzymes that activate other enzymes by covalent modification — phosphorylating a serine residue

But to get PTKs to work, you first need to bind a ligand But to get PTKs to work, you first need to bind a ligand. For example, the receptor tyrosine kinase (RTK), which is imbedded in a cell membrane (a transmembrane protein), binds insulin and switches conformation.

Kinetics of binding a ligand

Scatchard plot (b) yields the ligand binding constant KL B = [bound ligand] = [RL]; F = [free ligand] = [L] George Scatchard, 1949

The Ras signaling cascade regulates cell growth and differentiation: starts with an RTK

Another group of signal transduction molecules are heterotrimeric G proteins The structure of a heterotrimeric G protein, showing a bound GDP molecule

Adenylate cyclase (AC) catalyzes the production of cyclic AMP (cAMP) from ATP AC is activated by the binding of a heterotrimeric G protein

G protein coupled receptors contain 7 transmembrane helices

Figure 13-18

Adenylate cyclase synthesizes cAMP that activates protein kinase A (PKA)

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Figure 13-21b

The adenylate cyclase (AC) signaling system

Box 13-4a

Box 13-4b

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Box 13-5a

Box 13-5b