Figure 18-13
Schematic diagram of the major
enzymatic modification/demodification systems involved
in the control of glycogen metabolism in muscle.
Page 639
o= original
m=modified
Candace Parchen (BS Cell Molec. Biol. 2004) will give the Biology
seminar next Wednesday 2/10 (4pm in BI 234).
Title: The Effect of Phosphodiesterase 5 (PDE5) inhibitors on
Dystrophic Hearts
Annual T-shirt contest is underway. Strut your geeky stuff!!!!!
Page 641
Figure 18-14
X-ray structure
of the catalytic
(C) subunit of
mouse protein
kinase A (PKA).
PKs have KEY roles in signalling
1.7% of human genome = kinases
1000 putative kinase genes!
ATP
inhibitor
Figure 18-15 X-ray structure of
the regulatory (R) subunit of
bovine protein kinase A (PKA).
Page 641
Autoinhibitory domain
Fits in active site of C
Keeps complex inactive
Phosphorylase Kinase
• Senses Ca+2
– Activated by [Ca+2] as low as 10-7M!!
– 4 subunits (αβγδ)4 active structure a tetramer
of tetramers!
– Subunit γ has catalytic activity
– Others are inhibitory
– Subunit δ = Calmodulin (CaM)
Figure 18-16 X-Ray structure
of rat testis calmodulin.
4 binding sites for
Ca+2
Ca+2 binding induces
a conformational
change exposing a
met-rich hydrophobic
region.
Page 642
Flexible stalk
May be random coil really
Why would increased
[Ca+2 ]promote glucose
mobilization?
Nerve impulses into
muscle trigger Ca+2
release
methionine sulfur atoms
key nonpolar areas
In phosphorylase kinase, CaM-Ca+2 binds strongly to the
γ subunit and increases its activity.
The non-polar amino acids
form two neat grooves (red
stars) when calcium
binds,. Because these
non-polar grooves are
generic in shape,
calmodulin acts as a
versatile regulatory protein
and its targets are not
required to possess any
specific amino acid
sequence or structural
binding motifs.
Figure 18-17 EF hand, the
calcium binding site.
Page 642
Octahedral geometry for Ca+2
Page 643
Figure 18-18a. NMR structure of (Ca2+)4–CaM from Drosophila
melanogaster in complex with its 26-residue target polypeptide
from rabbit skeletal muscle myosin light chain kinase (MLCK). (a)
A view of the complex in which the N-terminus of the target
polypeptide is on the right.
Target peptide
Page 643
Figure 18-18b. NMR structure of (Ca2+)4–CaM from Drosophila
melanogaster in complex with its 26-residue target polypeptide
from rabbit skeletal muscle myosin light chain kinase (MLCK). (b)
The perpendicular view as seen from the right side of Part a.
Figure 18-19
Schematic diagram
of the Ca2+–CaMdependent activation
of protein kinases.
Figure 18-21
The antagonistic effects of insulin and
epinephrine on glycogen metabolism in muscle.
Phosphoprotein phosphatase
Page 645
2 Mn+2 activate water for
nucleophillic attack
Maintaining steady blood [glc]
Hi [glc] stimulates insulin
secretion
Page 648
Low [glc] stimulates
glucagon secretion
Figure 18-22
The enzymatic activities of
phosphorylase a and glycogen synthase in
mouse liver in response to an infusion of glucose.
Figure 18-23
Comparison of the relative enzymatic
activities of hexokinase and glucokinase over the
physiological blood glucose range.
Page 649
NOT inhibited by G6P
Page 649
Figure 18-24
Formation and degradation of -Dfructose-2,6-bisphosphate as catalyzed by PFK-2 and
FBPase-2.
These 2 activities
are located on 2
different domains
of the same
protein!
PKA is a ser kinase
It decreases PFK
activity and increases
FBPase activity.
Glucoagon Action in Liver vs.
Muscle
Liver
• ↑cAMP
• ↑PKA
• ↓[F2,6BP]
• glycolysis↓
Muscle
•↑ Glycogen breakdown
•↑glycolysis
HUH???
--Different isozymes
--Different phosphorylation sites
--Different Kinetics!!!
Figure 18-25 X-ray structure of
the H256A mutant of rat testis
PFK-2/FBPase-2.
Page 650
PFK 2
FBPase
Page 652
Figure 18-26b
The liver’s
response to stress.
(b) The participation
of two second
messenger systems.
Page 652
Figure 18-26a
The liver’s
response to
stress.
(a) Stimulation of
α-adrenoreceptors
by epinephrine
activates
phospholipase C
to hydrolyze PIP2
to IP3 and DAG.
Fig. 19-16 Receptor-mediated
activation/inhibition of
Adenylate Cyclase
Page 674
Figure 19-13
Activation/deactivation cycle for
hormonally stimulated AC.
Page 674
Figure 19-14 General structure
of a G protein-coupled receptor
(GPCR).
Page 708
Figure 19-51 Role of PIP2 in
intracellular signaling.
Page 682
Figure 19-21 Schematic diagram of a
typical mammalian AC.
Page 707
Figure 19-50
Molecular formula of
the phosphatidylinositides.
Page 709
Figure 19-52
A phospholipase is named
according to the bond that it cleaves on a
glycerophospholipid.
Page 713
Figure 19-57 Activation of
PKC.
Page 719
Figure 19-64 Insulin signal transduction.
Figure 18-27
The ADP concentration in human
forearm muscles during rest and following exertion in
normal individuals and those with McArdle’s disease.
Page 653
(Muscle Phosphorylase Deficiency)
Page 651
Table 18-1Hereditary Glycogen
Storage Diseases.
Figure 20.2
For diffusion Keq = 1, thus DG°’ = 0
Start of
“reaction”
equilibrium
For diffusion Keq = 1, thus DG°’ = 0
Figure 20.3
“non-mediated”
transport
Table 20-1
Figure 20.4
Figure 20-9
Valinomycin
(K+ complex)
Figure 20-9
Monensin
(Na+ complex)
a-hemolysin
(Staph. aureus)
“IONOPHORES”
Gramicidin A
See Figure 20.11
Figure 20.14
Figure 20.15
Figure 20.18
Table 20-3
Figure 20.21
Figure 20.27
“Alfonse, Biochemistry makes my head hurt!!”
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