Topic 15 - Fatty Acid Metabolism Flashcards
*Understand why lipids are a major energy source
Explain.
- FA are the most energy dense, due to highly reduced nature
=>contain 2x as much e for mass as CHD & proteins
=>play important role when CHD stores depleted -
Triacylglyerols are composed of 3 FA’s esterified to glycerol.
=>major fuel component is FA, not glycerol
*Describe action of lipases in hydrolysis of triacylglycerols
Describe a basic overview of the fate of dietary triacylglycerols
- TAG’s are digested by pancreatic lipase
- Produce FA, glycerol
- Products are absorbed by intestinal cells
- IC convert them back into TAGs and chylomicrons
- Chylomicrons are released into blood stream/lymph sys to adipose/skeletal muscle
- TAGs are hydrolysed to FAs & glycerol by lipoprotein lipase
- Skeletal muscle = FA degraded (b-oxidation), producing ATP
- Adipose = FA are re-esterified to TAGs for storage
*Describe action of lipases in hydrolysis of triacylglycerols
What do lipases do?
Lipases catalyse the hydrolysis of TAG’s to free fatty acids (FFA’s) & glycerol
What are chylomicrons?
- Type of lipoprotein
- Outer layer = phospholipids, apolipoproteins, cholesterol
- Inner layer = TAGs
- Fats are packaged this way as fats are hydrophobic
- Lipoproteins stabilise water-insoluble TAGs in blood stream
_*Describe action of lipases in hydrolysis of triacylglycerols_
Describe the function of pancreatic lipase
- Dietary TAG
- Hydrolyses dietary TAGs into FFAs & glycerol
- is NOT regulated by hormones
_*Describe action of lipases in hydrolysis of triacylglycerols_
Describe the function of lipoprotein lipase
- Hydrolyses dietary TAGs associated w/
- Chylomicrons
- Very low density lipoproteins (VLDL)
- Is NOT regulated by hormones
- >activity after meals as >substrate
_*Describe action of lipases in hydrolysis of triacylglycerols_
Describe the function of hormone-sensitive lipase
- Found in adipose
- Catalyses breakdown of stored TAGs to FFA & glycerol
- Regulation:
- activated by glucagon & adrenaline
- Glycerol is transported via blood to liver, enters glycolysis or gluconeogenesis
- FAs transported in blood to liver/skeletal muscle, used as fuel for b-oxidation
*Outline processes of b-oxidation in FA catabolism
Define b-oxidation and fatty acid catabolism. Where do these processes occur?
- b-oxidation: Process in which activated FA are broken down in the mitochondria to form acetyl-CoA
- FA catabolism: necessaru pathway for energy generation from fats when glycogen/glucose stores become depleted
- Occur in skeletal muscle & liver
_*Outline processes of b-oxidation in FA catabolism_
Define step 1 of FA catabolism
- FAs are activated by attachment of CoA
- Converted to fatty acyl-CoA by acyl-CoA synthetase in cytoplasm
- Requires ATP
_*Outline processes of b-oxidation in FA catabolism_
Define step 2 of FA catabolism
- The activated FA (fatty acyl-CoA) is transported to mitochondrial matrix via the carrier carnitine
_*Outline processes of b-oxidation in FA catabolism_
Define step 3 of FA catabolism
- In final cycle, 2 acetyl-CoA released
- 1 NADH & 1 FADH2 produced
- Series of 4 enzymatic steps
- 1. Oxidation
- oxidation of FA by acyl-CoA-DH. Catalyses formation of a = b/w C2 & C3
- 2. Hydration
- hydration of bond b/w C2 & C3 by enoyl-CoA-hydratase, forming L isomer
- 3. Oxidation
- oxidation of L-b-hydroxyacyl CoA by NAD+. This converts hydroxyl group => keto group. Catalysed by b-hydroxyacyl-CoA DH
- 4. Thiolytic cleavage
- cleavage of b-ketoacyl CoA by thiol group of another molecule of CoA. Thiol inserted b/w C2 & C3. Catalysed by thiolase
Please check lecture for slides 37 & 39 this is VERY IMPORTANT YOU CAN DO THIS CALCULATION
(n-2) / 2
C10 - 2 = 8
8 / 2 = 4 (4 rounds b-oxidation)
Always 1 round less than number of acetyl groups (or no# rounds + 1 = no# acetyl-CoA)
So = 5 acetyl-CoA
………………………………………………………
C14 = 7 rounds b-oxi
1 FADH2 & 1 NADH produced for every round
per FADH2 = 1.5 ATP
per NADH = 2.5 ATP
No# ATP ultimately formed
for NADH = 7x2.5 = 17.5
for FADH2 = 7x1.5 = 10.5
*Understand why ketone bodies are formed during FA metabolism
- By product of FA catabolism in liver
- H2O soluble compound
- Used as fuel
- Acetone, acetoacetate, b-hydroxybutyrate
- Formation:
- Two acetyl-CoA undergo conversion to acetoacetate
- Acetoacetate is converted to acetone or b-hydroxybutyrate
- Used as a soluble energy source during fasting
Briefly describe FA synthesis
- Glucose that can not be stored as glycogen is converted to acetyl-CoA via glycolysis, converted to FAs & esterified w/ glycerol to form TAG
- These TAGs are packaged into VLDLs for export
- TAGs present in VLDLs are hydrolysed by lipoprotein lipase to form glycerol & FFA
*Outline synthesis of triacylglycerols from surplus CHD
Think:
where does it occur?
actions of two major enzymatic complexes
- Occurs in liver, in CYTOPLASM of cells not mitochondria
- Involves two enzymatic complexes
- Acetyl-CoA carboxylase
- -FA synthase complex*
*Identify where FA synthesis/FA catabolism occurs
- Synthesis = liver
- Catabolism = skeletal muscle
_*Outline synthesis of triacylglycerols from surplus CHD_
Describe the actions of acetyl-CoA carboxylase
- =>uses cofactor biotin to carboxylate acetyl-CoA to malonyl-CoA. This activates or primes acetyl-CoA for subsequent condensation rxn
- Acetyl-CoA (2C) + HCO3 + ATP => Malonyl-CoA (3C) + ADP + Pi
_*Outline synthesis of triacylglycerols from surplus CHD_
Describe the actions of FA synthase complex
=> 4 enzymatic activities, involves esterification of 3 FAs => glycerol
=> M-CoA (3C) & a-CoA (2C) joined to produce 4C chain
=> CO2 released
=> 2 NADPH consumed
=> synthesised FAs esterified to TAGs
=> performed in liver & adipose
*Describe regulation of FA metabolism
Brief over view
- Oxidation of FA consumes precious storage fuel
- Regulated so ONLY occurs when needed
- Dependant on glucose levels
- ON = BGL <
- OFF = BGL >
_*Describe regulation of FA metabolism_
What do high glucose levels lead to?
- > FA synthesis
- < FA degradation
- > glucose stimulates insulin release
- Causes > in glycogen synthesis & glycolysis
- Activation of acetyl-CoA carboxylase
- Once cells fully saturated w/ glycogen, excess glucose is converted to pyruvate, acetyl-CoA & malonyl-CoA
- Malonyl-CoA is converted => FAs. Inhibits carnitine acyl-transferase required to transport fatty-acyl-CoA to mitochondria for oxidation, :: inhibits FA degradation
*Describe regulation of FA metabolism
What do low glucose levels lead to?
- < FA synthesis
- > FA degradation
- < glucose stimulates glucagon release
- Activates PKA
- glycogen breakdown -gluconeogenesis
- FA breakdown
- Glucagon activates hormone-sensitive lipase in adopocytes -mobilises FA to liver/muscle
- Inactivates acetyl-CoA carboxylase in liver -lowers malonyl-CoA levels & allows FA breakdown to occur in mitochondria
- Generates a lot of acetyl-CoA in liver, used in CA cycle & ketone body formation
- Hydrolyse fats stored in adipose tissue
- 1 FADH2 and 1 NADH
- Liver
