Topic 15 - Fatty Acid Metabolism Flashcards Preview

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Flashcards in Topic 15 - Fatty Acid Metabolism Deck (25)
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1
Q

*Understand why lipids are a major energy source

Explain.

A
  • 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
2
Q

*Describe action of lipases in hydrolysis of triacylglycerols

Describe a basic overview of the fate of dietary triacylglycerols

A
  • 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
3
Q

*Describe action of lipases in hydrolysis of triacylglycerols

What do lipases do?

A

Lipases catalyse the hydrolysis of TAG’s to free fatty acids (FFA’s) & glycerol

4
Q

What are chylomicrons?

A
  • 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
5
Q

_*Describe action of lipases in hydrolysis of triacylglycerols_

Describe the function of pancreatic lipase

A
  • Dietary TAG
  • Hydrolyses dietary TAGs into FFAs & glycerol
  • is NOT regulated by hormones
6
Q

_*Describe action of lipases in hydrolysis of triacylglycerols_

Describe the function of lipoprotein lipase

A
  • Hydrolyses dietary TAGs associated w/
  • Chylomicrons
  • Very low density lipoproteins (VLDL)
  • Is NOT regulated by hormones
  • >activity after meals as >substrate
7
Q

_*Describe action of lipases in hydrolysis of triacylglycerols_

Describe the function of hormone-sensitive lipase

A
  • 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
8
Q

*Outline processes of b-oxidation in FA catabolism

Define b-oxidation and fatty acid catabolism. Where do these processes occur?

A
  • 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
9
Q

_*Outline processes of b-oxidation in FA catabolism_

Define step 1 of FA catabolism

A
  • FAs are activated by attachment of CoA
  • Converted to fatty acyl-CoA by acyl-CoA synthetase in cytoplasm
  • Requires ATP
10
Q

_*Outline processes of b-oxidation in FA catabolism_

Define step 2 of FA catabolism

A
  • The activated FA (fatty acyl-CoA) is transported to mitochondrial matrix via the carrier carnitine
11
Q

_*Outline processes of b-oxidation in FA catabolism_

Define step 3 of FA catabolism

A
  • 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
12
Q

Please check lecture for slides 37 & 39 this is VERY IMPORTANT YOU CAN DO THIS CALCULATION

A

(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

13
Q

*Understand why ketone bodies are formed during FA metabolism

A
  • 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
14
Q

Briefly describe FA synthesis

A
  • 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
15
Q

*Outline synthesis of triacylglycerols from surplus CHD

Think:

where does it occur?

actions of two major enzymatic complexes

A
  • Occurs in liver, in CYTOPLASM of cells not mitochondria
  • Involves two enzymatic complexes
  • Acetyl-CoA carboxylase
  • -FA synthase complex*
16
Q

*Identify where FA synthesis/FA catabolism occurs

A
  • Synthesis = liver
  • Catabolism = skeletal muscle
17
Q

_*Outline synthesis of triacylglycerols from surplus CHD_

Describe the actions of acetyl-CoA carboxylase

A
  • =>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
18
Q

_*Outline synthesis of triacylglycerols from surplus CHD_

Describe the actions of FA synthase complex

A

=> 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

19
Q

*Describe regulation of FA metabolism

Brief over view

A
  • Oxidation of FA consumes precious storage fuel
  • Regulated so ONLY occurs when needed
  • Dependant on glucose levels
  • ON = BGL <
  • OFF = BGL >
20
Q

_*Describe regulation of FA metabolism_

What do high glucose levels lead to?

A
  • > 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
21
Q

*Describe regulation of FA metabolism

What do low glucose levels lead to?

A
  • < 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
22
Q
A
  1. Hydrolyse fats stored in adipose tissue
23
Q
A
  1. 1 FADH2 and 1 NADH
24
Q
A
  1. Liver
25
Q
A
  1. Occurs in the mitochondria