Ganong's Review of Medical Physiology, 23rd Edition

is activated by heterotrimeric G proteins, while PLCγ forms are
activated through tyrosine kinase receptors. PLC isoforms can
catalyze the hydrolysis of the membrane lipid phosphatidylinositol
4,5-diphosphate (PIP 2 ) to form IP 3 and diacylglycerol
(DAG) (Figure 2–25). The IP 3 diffuses to the endoplasmic
CHAPTER 2 Overview of Cellular Physiology in Medical Physiology 55
D
P V H S G N T T L L F D S D N G P P G M NH2 H
D
V
T
E
E
R
D
E
A
W
W
M
V
V
G M A L I N
I L M S B A G F
V I V P V V
L A I V A L G M
F G N V L D
V L V I A C A L
T A I S T I
A
K
F
N F C
D
I
A
K
G Q
N
F
H
K
W
T
A
M
C
R
E F W
T S I D
V L C
V T A S
I E T
L C V I
A V D
F
Y
N
E T
R L Q T V Y H K
E
TC
C
D
F
F
T
D
N
Q
Y W H Q A Y
M Q I P A I A S
L F S S I V
T L Q S S F Y V
V I W P L V
V M L I V M V F
V M R V Y S L
R A
R
T
Y
K
K
V
I
L
N
A
F
K
A
K
H
E
Q K L
I
T
V C
A K R Q L Q
F
K
K
T
L
I
S L
S
P S D
F K Y Q H E S K
S
S
F R G
R
P
R
N L G Q V E Q D G R S G H G L
N L S R V V C T K N S F P V Y F N P G E T G N M NH2 P
F
E
A
2-Adrenergic receptor
P
S
C
Q
Q
Extracellular
Y
G
F P
T
M
Y
surface
V G
G
L
F
C
E
A
Y
N
P
E
L
G
I
I P
E
H
Y
P W L G
R
K
Q S
S
I V H E V Y
F S M T Y L F A T
V I N V I L L N
L A A Y T T T F L G G E
I F F W L G
M F L Q G F I A L
P L W C Y V N S
L I M L V M F L W S L A
L T F A F N
G F P D A V V L A
T G M I P L I Y
I N F L A L N L I E R Y
I G C R S T L Y L I Y V V V
P
D F R
V
N
I A F Q
T
L
E
V
P
L
Q T
H K K L R
L
C
Cytoplasmic
L
surface
R
R
S
S
S
A E G M Y D T K G N G N S S Y G N G Y A K
S
G
C
Q
L G Q E K E S E R L C E D P P G T E S F V N C
Q
L P S D N T S C N R G Q S D L S L S P V T
G
HOOC
C G I
D
Y
Y
T
P
H
E
E
G
T
Q S
D
N
H F
G
N
T
P
W G V E S F F I Y I F M
L P P A V I Y M F A V Q T I P A
A C A F V V A Y P F F A
L A M V H F I I L W C I K T S A
W T F P L I L F A V Y N
A V G M V I F F I V M I P V I Y
I A H C Y G I V M I M M
C
N
Q
R
N
K
E
T
K Q
L
F R N
V
C
E
M
P G
V
K E A
M F
S N F R
F
K
V
Q
T T
T
V
T
K
E
T
A A
A
L
A Q Q Q E
S
C
C
G
D D N K
Intradiskal
Rhodopsin
surface
F
Cytoplasmic surface
HOOC A P A V Q S T E T K S V T T S A E G L P
FIGURE 2–24 Structures of two G protein-coupled receptors. The individual amino acid residues are identified by their single-letter codes,
and the orange residues are sites of phosphorylation. The Y-shaped symbols identify glycosylation sites. Note the extracellular amino terminal, the
intracellular carboxyl terminal, and the seven membrane-spanning portions of each protein. (Reproduced with permission from Benovic JL et al: Light-
dependent phosphorylation of rhodopsin by β-adrenergic receptor kinase. Reprinted by permission from Nature 1986;321:869. Copyright © 1986 by Macmillan Magazines)
Phosphatidylinositol
(PI)
P
1
4
P
1
4
P
Inositol IP
+
CDP-diacylglycerol
reticulum, where it triggers the release of Ca 2+ into the cytoplasm
by binding the IP 3 receptor, a ligand-gated Ca 2+ channel
(Figure 2–26). DAG is also a second messenger; it stays in
the cell membrane, where it activates one of several isoforms
of protein kinase C.
PIP PIP2 Diacylglycerol
FIGURE 2–25 Metabolism of phosphatidylinositol in cell membranes. Phosphatidylinositol is successively phosphorylated to form
phosphatidylinositol 4-phosphate (PIP), then phosphatidylinositol 4,5-bisphosphate (PIP2). Phospholipase Cβ and phospholipase Cγ catalyze the
breakdown of PIP2 to inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. Other inositol phosphates and phosphatidylinositol derivatives can also
be formed. IP3 is dephosphorylated to inositol, and diacylglycerol is metabolized to cytosine diphosphate (CDP)-diacylglycerol. CDP-diacylglycerol
and inositol then combine to form phosphatidylinositol, completing the cycle. (Modified from Berridge MJ: Inositol triphosphate and diacylglycerol as second
messengers. Biochem J 1984;220:345.)
P
1
4
P
Phospholipase
C
IP 2
5
P
Phosphatidic acid
P
1
4
P
IP 3
5
P