Lipids 2: Lipopysis And B Oxidation

Question 0

Fat oxidation

Conversion of TAG into NEFA

Answer 0

The Oxidative process
Conversion of TAG into NEFA
-The key step in determining the rate of fat catabolism in the animal is the rate at which NEFA are produced, there are 2 primary sources of NEFA:
Firstly lipolyis➡ is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids, followed by degradation into acetyl units by beta oxidation.
Esterification: a chemical reaction resulting in formation of at least one ester product (ester is the bond between fats)

1. Fat metabolism in adipose tissue- the balance between lipolysis and esterification: 
TAG ➡ lipolysis ➡ 3 NEFA + glycerol
Positive stimulation to do this is: 
-glucagon 
-adrenalin 
-growth hormone 
-ACTH
Negative: insulin 

3 NEFA + glycerol ➡ esterification ➡ TAG 
Negative (inhibits) 
-glucagon 
-growth hormone 
-adrenalin 
-ACTH
Positive: insulin 

2. Lipolysis in the blood (dietary and liver derived TAG)
   - non esterfied fatty acids are either transported as triacylglycerol incorporated within a lipoprotein or as non sterilised fatty acids (NEFAs) bound to albumin.

• lipoproteins in blood are small water soluble particles that are designed to carry TAG or cholesterol in the blood,
• chylomicrons and VLDL both carry TAG
• many tissues accept liver have lipoprotein lipase on capillary wall
• lipoproteins will come past and bind to the lipoprotein lipase
• LPL will then cleave TAGS➡ 3 NEFAs and glycerol

Question 1

Fat oxidation yields?

Can provide up to?

Answer 1

• Oxidation yields CO2, H2O and energy
• fat is an efficient fuel
• can provide up to 50% of VO2 max

Fat as a fuel: 2x the energy of carbs
-more reduced, greater number of electrons to be disposed of

Large energy store:
Glycogen stores in liver last 1-2 days of fasting
-fat stores last about 1 week

Question 2

Tell me the lipids and the lipid class carried.
For: 
Chylomicrons 
Very low density lipoproteins 
Low density lipoproteins 
High density lipoproteins 

Tell me their lipid class carried

Answer 2

Tell me the lipids and the lipid class carried.
For:
Chylomicrons➡ triacylglycerol; gut➡ extra hepatic tissues
Very low density lipoproteins (VLDL) ➡ triacylglycerol; liver ➡ extra hepatic tissues
Low density lipoproteins (LDL).
Lipid class carried: cholesterol ester; gut, liver (formed in plasma) ➡ tissues with LDL receptor
High density lipoprotein (HDL)
Lipid class carried:
Cholesterol ester; liver ➡ tissues ➡ liver

Question 3

We will be mainly focusing on the chylomicrons (made by the small intestinal mucosa) and VLDL (made by the liver) since they are the primary carriers of triacylglycerol. Tell me about these lipo proteins

Answer 3

These lipoproteins enter the blood and carry dietary fat (chylomicrons) or fat synthesised from glucose in the liver (VLDL) to the tissues.
-many tissues (except the liver) have the enzyme lipoprotein lipase located on the capillary wall.
-as a chylomicron or VLDL passes it, it binds to the lipoprotein lipase and the triacylglycerol is cleaved to NEFAs plus glycerol.
-the NEFAs pass into the cells nourished by the capillaries and to a lesser extend into the circulation
Look at pg 44

Question 4

Describe the catabolism of NEFAs.

Tell me how the system is activated and transported into the mitochondria.

Answer 4

1. Formation of CoA derivative ie activated NEFA
   NEFA + ATP + CoA ➡ NEFACoA + AMP + PPi
   This reaction occurs in the cytosol and the next the NEFACoA must be transported into the mitochondria
2. Transportation of NEFACoA into the mitochondria occurs by CPT1, so regulation of NEFA transport into the mitochondria is regulated by this. CPT1 is inhibited by malonyCoA which is a metabolite of fatty acid biosynthesis so can’t happen at the same time.
3. B oxidation
   Located within the mitochondria and on the inner surface of the inner mitochondrial membrane. The pathway involves oxidation of the B carbon consists of 2 parts
   A) oxidative of the NEFA CoA to form acetyl CoA and reduced electron carriers (NADH and FADH) it yields one of each
   -oxidation of acetyl pCoA via the TCA cycle
   Each of the B oxidation yields 1 acetlyCoA plus 1 NADH and 1 FADH. The cycle is continuous only until acetlyCoA is left. Regulation is via substrate supply ie NEFACoA, NAD and FAD- the later are supplied by oxidative phosphorylation so the pathways is indirectly dependant in a supply of O2 and ATP turnover.

Constraints:

• aerobic
• several tissues cannot use fat (glucose dependant ones)
• limited power (low ATP/min) and slow to accelerate (ie need about 30 mins to react maximum fat mobilisation during exercise.

Question 5

Check out the diagram of the overall control of fat oxidisation

Answer 5

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