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Fundamentals of Biochemistry

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

2 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.

3 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.

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

5 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.

6 Kinetics of binding a ligand

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

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

9

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

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

12 G protein coupled receptors contain 7 transmembrane helices

13 Figure 13-18

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

15 Figure 13-21

16 Figure 13-21b

17 The adenylate cyclase (AC) signaling system

18 Box 13-4a

19 Box 13-4b

20 Page 436

21 Figure 13-24

22 Figure 13-25

23 Figure 13-26

24 Figure 13-27

25 Figure 13-28

26 Figure 13-29

27 Page 441

28 Figure 13-30

29 Figure 13-31

30 Box 13-5a

31 Box 13-5b


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