Term
Lipid Metabolism
Fed State |
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Definition
-1.Absorption of Lipids and Carbohydrates
-Lipids are packaged as lipoproteins (see C1-70, 71B).
-Carbohydrates dropped into the bloodstream.
2.Insulin stimulates metabolism of lipoproteins and uptake of carbohydrates.
3.Metabolism of lipids and carbohydrates into storage molecules (fatty acids).
-Fatty acids are made from acetyl-CoA
-Formation of malonyl-CoA
-Synthesis of fatty acid via 2-carbons additions
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Term
Lipid Metabolism
Fatty Acid Synthesis |
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Definition
-Fatty acid synthase resides in the cytoplasm.
-Fatty acid synthesis takes several steps but all reactions take place on one multifunctional enzyme.
-Sequential addition of malonyl-CoA with CO2 release.
-Thus, 2-carbons are added to the growing chain with each cycle.
-Synthesis ends with formation of palmitate (16 carbons).
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Term
Formation of Malonyl CoA
A Regulated Step |
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Definition
-Acetyl Co-A Carboxylase catalyzes the rate limiting step of fatty acid biosynthesis.
-High Citrate from TCA activates.
-relates fed state to FA synthesis
-Citrate acts in Acetate Shuttle
-Feedback Inhibition
-Palmitoyl-CoA
Hormonal Control:
Fed Signals Activate
-Insulin
Fasting Signals Repress
-glucagon and epinephrine
Hormonal control prevents a futile cycle between b-oxidation and fatty acid synthesis.
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Term
Lipid Metabolism
Fatty Acid Synthesis
Fatty Acid Synthase
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Definition
1. Add Acetyl-CoA
2. Add Malonyl-CoA to
Acyl carrier protein.
3. Condensation and release
CO2.
4.Reduction.
5.Dehydration.
6.Reduction
Repeat up to 16 carbons and palmitate is released.
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Term
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Definition
Citrate has a transporter and is degraded in cytosol to acetyl-CoA and oxaloacetate.
Oxaloacetate must be reduced to malate which can re-enter the mitochondria or
be converted to pyruvate.
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Term
Acetate Shuttle
Produces NADPH |
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Definition
The oxaloacetate can be reduced
and transported back into the
mitochondria.
Or,
Malic enzyme can convert malate
to pyruvate for transport back
into the mitochondria.
-Reactions using the malic enzyme convert
NADH into NADPH.
NADPH is used in anabolic pathways including FA synthesis.
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Term
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Definition
-Primarily in liver
•A small fraction of cholesterol made is incorporated into the membranes of hepatocytes
•Most is exported.
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Term
Cholesterol is made from acetyl-CoA in four stages |
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Definition
-Three acetate units condense to form a six carbon intermediate, mevalonate
-Conversion of mevalonate into activated isoprene units
-Polymerization of six 5-carbon isoprene units to form the 30-carbon linear structure of squalene.
-Cyclization of squalene forms the four rings of the steroid nucleus.
Subsequent modifications leads to the final product, cholesterol.
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Term
Cholesterol Biosynthesis
Regulation |
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Definition
HMG-CoA reductase is regulated by:
•Protein stability
•Feedback Inhibition
•Gene transcription
•Hormonal Control
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Term
HMG-CoA reductase is regulated by cholesterol or cholesterol derivative at several levels |
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Definition
-•Cholesterol, or a cholesterol derivative, promotes rapid degradation of the enzyme (via the ubiquitin-proteasome pathway) and inhibits transcription of its gene.
•Feedback inhibition.
Cholesterol inhibits
HMG-CoA reductase
activity.
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Term
HMG-CoA reductase
Hormonal Control |
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Definition
•Glucagon stimulates phosphorylation and is inhibitory
•Insulin stimulates dephosphorylation and is activating.
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Term
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Definition
1. Bile salts – amphipathic cholesterol derivatives
that aid lipid digestion
2. Cholesteryl esters (storage form of
cholesterol)– Addition of fatty acid to the
cholesterol. The cholesterol ester is much more
hydrophobic and can be transported in
lipoprotein particles to other tissues or are stored
in the liver.
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Term
Cholesteryl Ester Formation |
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Definition
-Formed in the liver by acyl-CoA-cholesterol acyl transferase (ACAT), which transfers a fatty acid from coenzyme A to the –OH group of cholesterol.
-Converting cholesterol to a more hydrophobic form.
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