Term
Lipid Metabolism
Fasted State |
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Definition
1.Increase of glucagon and epinephrine and reduction in insulin.
2.Glucagon and epinephrine stimulate triglyceride breakdown.
- increases intracellular cAMP and activates protein kinase A.
-phosphorylation and activation of hormone sensitive lipase.
-degrades triglycerides to free fatty acids and glycerol.
3.Free fatty acids and glycerol diffuse to blood.
-Fatty acids bind to serum albumin; glycerol is soluble.
4. In liver, glucagon and epinephrine stimulate fatty acid oxidation to form ketone bodies and glycerol is used in gluconeogenesis.
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Term
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Definition
-Perilipin is a protein that coats the lipid droplet in adipocytes.
Phosphorylation of perilipin is essential for hormone sensitive lipase to act.
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Term
Fasted State
Triacylglycerol/Fatty Acid Cycle* |
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Definition
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-Up to 60% of fatty acid mobilized from adipose that is taken up by the liver is repackaged into lipoproteins and transferred back to the adipose.
1.Adipose releases much more free fatty acid than required for
metabolism.
2.The liver re-esterifies the fatty acids into triglycerides, packages the
lipid into lipoproteins and secretes it into the bloodstream.
3.Requires energy (~3 to 6%) of energy in the fatty acid but ensures
-adequate energy supply.
-maintains blood homeostasis with respect to serum lipid.
-aids in delivery of fatty acids via lipoproteins.a
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Term
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Definition
-Once the fatty acid is taken into the cell, catabolism releases
the stored energy.
-Catabolism of fatty acids occurs in the mitochondria where
the long acyl chain is broken down into acetyl-CoA.
-The acetyl-CoA enters the Krebs cycle,
where the carbons are oxidized to CO2
-the energy transferred
to NADH and FADH2 for ATP production in the electron
transport chain.
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Term
Utilization of Fatty Acids for Energy
Mitochondrial Transport* |
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Definition
-Carnitine acyltransferase I on cytoplasmic face.
-Carnitine acyltransferase II inside the mitochondria.
-Carnitine acyltransferase I & II, aka, carnitine palmitoyltransferase I & II
are essential for long chain fatty acids 12-18 carbons. Short chain fatty
acids diffuse into the matrix and are conjugated to CoA.
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Term
Utilization of Fatty Acids for Energy
General(Beta Oxidation) |
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Definition
-Overall point is to degrade the long
fatty acyl-CoA to acetyl-CoA.
-Feed the acetyl-CoA into the TCA
and make ATP in the ETC.
-β Oxidation because the b position
is oxidized.
-The major point is that the fatty acid
gets cleaved into acetyl Co-A.
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Term
What if chain is monounsaturated or polyunsaturated? |
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Definition
-Monounsaturated FA
Add an isomerase to move the cis bond to trans.
-Polyunsaturated FA
Need an isomerase and a reductase.
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Term
βOxidation of Fatty Acids to Acetyl-CoA
Odd Chain Fatty Acids |
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Definition
-When life gives you propionyl-CoA,
make a TCA intermediate.
-With odd chain fatty acids, the final
product is 3-carbons (propionyl-CoA).
-With odd chain fatty acids, the last
product contains three carbons.
-Use a biotin mediated carboxylation
to make a four-carbon TCA
intermediate, succinyl-CoA.
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Term
Ketone Bodies
Brain Food and Bad Breath |
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Definition
-The liver produces ketone bodies from acetyl-CoA.
-The ketones produced, acetone, acetoacetate and
D-b-hydroxybutyrate are exported to extrahepatic tissues.
-The brain, which preferentially utilizes glucose,
will use ketone bodies under low glucose levels.
-Many peripheral cells will utilize ketone bodies, preserving glucose for the brain.
-Acetone although produced in smaller quantities than the other ketone bodies is volatile and is exhaled.
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Term
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Definition
-In liver during fast (glucagon),
gluconeogenesis removes oxaloacetate.
-Oxaloacetate removal slows TCA
promoting acetyl-CoA accumulation.
-Thus,acetyl-CoA from b-oxidation of FA
accumulates and is used to make
ketones.
-Ketones exported for fuel.
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Term
Ketone Bodies Clinical Correlation
Diabetic Ketoacidosis (DKA) |
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Definition
-In DKA, absence of insulin leads to high blood glucose and
production of ketone bodies.
-Absence of insulin= unchecked gluconeogenesis and glucose uptake goes down=high blood glucose levels.
-High blood glucose leads to dehydration-
glucose in urine pulls water,
osmotic diuresis that leads electrolyte
imbalance.
-Blood volume declines.
Tissues dehydrate due to high serum
osmolarity.
-Ketone bodies contribute to high serum
osmolarity and ketoacids drop blood pH.
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Term
Vitamin B12 Deficiency
Two Problems |
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Definition
-*Folate Trap causes megaloblastic anemia.
Same anemia as in oroticaciduria I and II from Uridine synthesis (Nucleotides).
- Folic acid supplementation can reduce or block the anemia.
- In oroticaciduria I and II the anemia is resistant to folate or B12 supplementation.
- Similar symptoms suggest the anemia is related to nucleotide synthesis thru lowering of folate pools.
-*Vitamin B12 deficiency also causes demyelination of neurons.
- May be due to methylmalonyl-CoA accumulation which effects formation of malonyl-CoA, which is essential to fatty acid synthesis and alters sphinglolipid synthesis (cerebrosides, gangliosides etc.).
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