Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 2Overview of Cellular Physiology in Medical Physiology 55

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 phosphatidyl-
inositol 4,5-diphosphate (PIP 2 ) to form IP 3 and diacylglycerol
(DAG) (Figure 2–25). The IP 3 diffuses to the endoplasmic

reticulum, where it triggers the release of Ca2+ into the cyto-

plasm by binding the IP 3 receptor, a ligand-gated Ca2+ chan-

nel (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.

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)

HDPVHSGNTTLLFDSDNGPPGM

VD

TE

ER

DE

WA

VV

IGLMMAS

VIV

VFLGVNI

TAI

LAIV

BLAIGNF

PVV

AVCLADL

STI

ALGM

NH 2

AK

F

MW

NFGN

FW

KM C

ERLQTVTN

FY

TESFIWD

VLC

LICEVTI

AVD

VTAS

AR

HT

KQ

AI

DCYHKET

CC

DF

FT

YWH N

MLQFISP

VVMILWI

VMR

TLQS

RY

IA

TI

SPF

KYQS

LL

KT

KN

A

AQIAAYS

SIV

VPMLVVF

VYSL

SFYV

RV

FQV

AKRQ

GQVEQDGRSG

LQKI

ESKD

RR

SS

KLCFK

AKHE

KL

T

HGL

PSHFRG

NL

QDN

LIP

IVH K

VIIFNFV

TLGTMFI

IG

PLWC

SPD

FRIAFQ

EL

LC

LR

R

IELVLYN

WLG

PALFINY

CR

YVNS

GY S

S

EGMYDTKGNGNSSYGN AKS

QEKESERL

GSA

CQ

LG TESFVNCQ

G

EDPPG

QSDLSLSPVT

C

HOOCLPSDNTSCNRG

 2 -Adrenergic receptor

Extracellular

surface

Cytoplasmic

surface

PSRVVCTKNSFPVYFNPGETG

EF

AP

QY

YL

AE

PW

QFSM

LMAFALY

IGNFFPL

TLY

LIML

TTTYTLF

QGF

ADLANVL

LIY

VMFL

NMNH 2

VT

V

GH

F

FY

V

GP

LE

GC

T

N

LS G

QHKKLRTP

NL

LFGAGTE

IAL

IVELRAY

VVV

WSLA

RS

IY

QM

C

EP

G

SCGIDY

YT

PH

EE

TN

WGV N

LAPCPAA

AWVTGFM

IAH

LAMV

CK

PMSNFRFG

NE

VEISYFM

FVV

VPILFIF

CYG M

HFII

QL

VF

TV

KEAAAQQQE T

T

SA

KEAKQ

TVE

R

T

HQGSDF

GP

FFAIVYQ

AYP

ILVFMAI

IV

LWCI

MN

KQFRNCM

VT

TL

CC

G

TIIFPMA

FFA

PVVYINY

IM

KTSA

HOOCAPAVQSTETKSVTTSAEDDGLPNK

Intradiskal Rhodopsin

surface

Cytoplasmic surface

F

FIGURE 2–25 Metabolism of phosphatidylinositol in cell membranes. Phosphatidylinositol is successively phosphorylated to form
phosphatidylinositol 4-phosphate (PIP), then phosphatidylinositol 4,5-bisphosphate (PIP 2 ). Phospholipase Cβ and phospholipase Cγ catalyze the
breakdown of PIP 2 to inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol. Other inositol phosphates and phosphatidylinositol derivatives can also
be formed. IP 3 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

P

1

4

P

P P

1

4 5

5

P

P P

1

4

Phosphatidylinositol

(PI)

PIP PIP 2 Diacylglycerol

IP 2

IP 3

Phospholipase

C

Inositol IP

CDP-diacylglycerol Phosphatidic acid

+