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Control of Fatty Acid Synthesis vs. Oxidation
When Insulin is HIGH --> fatty acid synthesis occurs
When Glucagon is HIGH --> lipolysis, fatty acid B-oxidation, ketogenesis occur
**These never happen at the same time!
Lipolysis
Process of releasing free fatty acids from triacylglycerols stored in the adipose IN THE
FASTED STATE
Steps of lipolysis
1) Hormone Sensitive Lipase: activated by glucagon and epinephrine
TAGs are hydrolyzed into FFAs and glycerol (inhibited by insulin)
2) Long chain FFAs travel bound to albumin to peripheral tissues to be used as energy
source
3) Glycerol travels to liver to be used as gluconeogenesis substrate
4) Acyl-CoA Synthetase: can reconvert FFAs to acyl-CoA to be used for re-esterification
in the adipose (continuous cycle of lipolysis & re-esterification)
Beta Oxidation
Process of generating acetyl-CoA, NADH, and FADH2 from the oxidation of FFAs taken
up by peripheral tissues (mostly liver & skel. muscle tissue).
Happens in mitochondria. Long chain FFAs cannot cross the mito membrane, so a
transport system is in place.
Ketogenesis
Process of generating ketones from excess acteyl-CoA produced from Beta-Oxidation
Mitochondrial pathway
Ketones can be used as fuel by other tissues but cannot be oxidized by...
The liver.
Skeletal muscle can oxidize ketones.
The brain will oxidize ketones when starving.
Ketogenesis is regulated by...
1) Activity of lipolysis
2) Cytosolic levels of malonyl-CoA (which inhibit CPTI)
3) Flux through the TCA depending on NADH levels & concentration of intermediates
(especially OAA)
Ketoacidosis can occur from prolonged ketogenesis, such as...
During starvation and uncontrolled diabetes
Important connections between Beta-Oxidation and other pathways
1) It supplies high levels of ATP in the fasted state
2) ATP is required for both process of glucose synthesis via gluconeogenesis & nitrogen
disposal via the urea cycle
, 3) deficiencies in beta-oxidation can result in hypoglycemia due to inability to support
glucose synthesis (such as CPTI deficiency, or medium chain acyl-dehydrogenase
deficiency)
Fatty Acid Synthesis: Activators & Inhibitors
Activated by insulin
Inhibited by glucagon
Fatty acid synthesis takes place in the...
Cytosol
Fatty acid synthesis: what occurs in the mitochondria?
Substrates need to be shuttled out of the mitochondria
In the mito:
-Acetyl-CoA and OAA in the mito --> citrate
-Tricarboxylate transporter --> removes excess citrate from the mito
Fatty acid elongation
Requires malonyl-CoA, fatty acyl-CoA and NADPH.
This pathway determines the chain length for fatty acids (medium, long, etc.)
Fatty acid synthesis connection to the PPP
PPP provides glycerol (for TAG synthesis) and NADPH (for fatty acid synthesis)
Fate of newly synthesized fatty acids
-Fatty acids are NOT stored in the liver
-instead, they're packaged into VLDL particles as TAGs (along with cholesterol) and are
transported to adipose for storage
HDL:
Origin, Primary Apo Protein, Composition, Primary Role
Origin: Liver
Primary Apo Protein: ApoA
Composition: Cholesterol and Cholesteryl Ester > Triacylglycerol (C and CE > TG)
Primary Role: reverse cholesterol transport
*HDL is the most dense
LDL:
Origin, Primary Apo Protein, Composition, Primary Role
Origin: Maturation of VLDL
Primary Apo Protein: ApoB100
Composition: Cholesterol and Cholesteryl Ester > Triacylglycerol (C and CE > TG)
Primary role: cholesterol transport from the liver
VLDL:
Origin, Primary Apo Protein, Composition, Primary Role
Origin: Liver
Primary Apo Protein: ApoB100
Composition: Triacylglycerol > Cholesterol and Cholesteryl Ester (TG > C and CE)
Primary role: carries newly synthesized TAG from the liver to the adipose