LIPID REGULATION

1
BIOC 460 DR. TISCHLER LECTURE 32
LIPID REGULATION
2
OBJECTIVES
1. Describing the events associated with covalent
modification of hormone-sensitive
lipase 2. Identify the mechanism by which
activators or inhibitors of phosphodiesterase
affect the activity of hormone-sensitive
lipase 3. List the factors that induce
(increase synthesis) or repress (decrease
synthesis) acetyl CoA carboxylase and
fatty acid synthase. 4. Describe the events
associated with polymerization-depolymerization
of acetyl CoA carboxylase 5.
Discuss the events associated with covalent
modification of acetyl CoA
carboxylase 6. Discuss the events associated
with covalent modification of HMG-CoA
reductase
3
CoA ATP
Palmitoyl-CoA
Palmitic acid (palmitate)
malonyl CoA inhibition prevents oxidation
activation
CPT-I
14 NADPH 7 malonyl CoA 1 acetyl CoA (7
cycles total)
Palmitoyl-carnitine
6 more cycles
mitochondrial transport
Palmitoyl-CoA
Butyryl-CoA
Mitochondrial process
FAD
oxidation
NADP
reduction
FADH2
NADPH
Cytosolic process
hydration
H2O
H2O
dehydration
NAD
oxidation
NADP
reduction
NADH
NADPH
thiolysis
CoA
condensation
Malonyl CoA
Acetyl CoA
6 more cycles
8 Acetyl CoA 7 FADH2 7 NADH (7 cycles total)
Figure 1. Parallel comparison of synthesis and
oxidation of palmitate.
4
cell membrane
HORMONES
Epinephrine Glucagon
Adenylyl cyclase


protein kinase A
inactive
active
RECEPTORS

activation
-
inhibition

Figure 2. Hormonal activation of triacylglycerol
(hormone-sensitive) lipase. Hormone signals from
epinephrine or glucagon promote mobilization of
fatty acids (lipolysis) via production of cyclic
AMP. Activated protein kinase A, phosphorylates
HSL-b to the active HSL-a form .
5
Table 1. Long-term control by induction or
repression of acetyl CoA carboxylase and fatty
acid synthase
PHYSIOLOGICAL CONDITION EFFECT
High-carbohydrate, low-fat diet ?
synthesis High-fat diet ? synthesis Fasting
? synthesis
6
Figure 3a. Regulation of acetyl CoA carboxylase
by citrate and palmitoyl CoA via polymerization
and depolymerization
7
Pi
ADP
ATP
Figure 3a. Regulation of acetyl CoA carboxylase
by citrate and palmitoyl CoA via polymerization
and depolymerization
8
Figure 3b. Regulation of acetyl CoA carboxylase
by glucagon, epinephrine, insulin and AMP
9
High Cholesterol
SREBP, sterol regulatory element binding protein
NUCLEUS
Low Cholesterol
ENDOPLASMIC RETICULUM
synthesis of HMG CoA reductase
mRNA for HMG CoA Reductase
Figure 4. HMG CoA reductase is induced when
intracellular cholesterol becomes too low while
with high cholesterol SREBP is bound to the
endoplasmic reticulum and is thus rendered
ineffective (not on exam)
10
Figure 5. Regulation of HMG CoA reductase
activity by phosphorylation in response to
glucagon or epinephrine
11
Figure 5. Activation of HMG CoA reductase by
dephosphorylation in response to insulin
RK
(active)
ADP
OPO3
RKK
(active)
ATP
12
(No Transcript)