Lecture No. 18 Hormonal Regulation of Fatty Acid Biosynthesis
Lecture No. 18 Hormonal Regulation of Fatty Acid Biosynthesis
Lecture No. 18 Hormonal Regulation of Fatty Acid Biosynthesis
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Hormonal regulation of fatty acid biosynthesis
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Regulation in General
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Regulation of Lipid Metabolism
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Lipid Metabolism
• Main processes:
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1) Absorption and Transport
• The main products of fat
digestion are free FA and
2-monoacylglycerols
(produced by the action of
pancreatic lipase)
• After absorption, FA is
activated to acyl-coenzyme A
(in the ER) which then reacts
with 2-monoacylglycerol to
form triacylglycerol
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Absorption and Transport
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Regulation at the Level of LPL
X
• In contrast, the amount of LPL in heart is decreased by insulin
and increased by starvation
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2 a) FA release from Adipose Tissue
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Regulation at the Level of Hormone- Sensitive
Lipase
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Mechanism
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• B) Insulin is released after Glc and AA
intake and signals the abundance of
dietary nutrients that are eligible for
storage
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C) Glucocorticoids, growth hormone, and the thyroid
hormones facilitate lipolysis by inducing the synthesis
of lipolytic proteins:
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2b) β-oxidation
• FAs are activated to acyl-
CoA by enzymes on the ER
membrane and
transported into the
mitochondrion by carnitine
• β-oxidation produces:
– acetyl-CoA, NADH,
FADH2
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Regulation of FA Oxidation
• A) Use of FAs by the tissues is proportional to the plasma FFA
level; therefore, FA oxidation is regulated at the level of HSL
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After a
carbohydrate-rich
meal
During fasting
• B) Carnitine-palmitoyl transferase I (CPT1) is inhibited by
malonyl-CoA that is formed in the FA biosynthesis by acetyl-
CoA carboxylase β-oxidation is inhibited when FA synthesis
is active
carboxylation
acetyl-CoA malonyl-CoA CPTI β-oxidation
ACC
– Thus, in the fed state, nearly all FAs entering the liver are esterified to
acylglycerols and transported out of the liver in the form of VLDL
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3) FA Biosynthesis
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malonyl-ACP + acetyl-ACP
– CO2
reduction
dehydration
reduction
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1) Acetyl-CoA carboxylase is allosterically activated by
citrate and inhibited by CoA-thioesters of long-chain FAs
such as palmitoyl-CoA (well-fed liver has a higher citrate
level and lower acyl-CoA level than does the fasting liver)
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• 2) acetyl-CoA carboxylase is stimulated by insulin and
inhibited by glucagon and epinephrine
– glucagon and epinephrine mediate activation of the
cAMP-dependent protein kinase A, which inactivates ACC
– insulin antagonizes this cascade by inducing
phosphodiesterase that degrades cAMP
– insulin stimulates the synthesis of ACC and fatty acid
synthase, starvation inhibits it (long-term regulation)
• Thus, cAMP-dependent phosphorylation simultaneously
inhibits FA synthesis and stimulates FA oxidation (by
activation of HSL)
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• 3) acetyl-CoA carboxylase is inhibited by phosphorylation
by the AMP-activated protein kinase (AMPK)
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Regulation of ACC – Overview
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Long-term Regulation
• Starvation and/or regular exercise, by decreasing the
glucose concentration in the blood, change the body‘s
hormone balance
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insulin
-
glucagon, + -
epinephrine
+
insulin +
- AMP-dependent -
insulin
phosphorylation
FA oxidation
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Adipose tissue as an endocrine organ
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Leptin
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Summary
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Summary
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