Lypolysis and β-Oxidation

Hi, this post will cover how fat is used as an energy source.

Fat as a Substrate for Metabolism

Lipids are twice as energy dense as glycogen on a dry matter basis and are six times as energy dense on a wet matter basis. Thus, lipids are used to store energy in the body. It is known that an average person has enough glycogen to last for one day without eating, while they'll have enough lipids stored to last one or two months!

Lipids are used during:

• a high fat diet
• fasting
• sustained exercise
• lactation
• late pregnancy
• a cold air temperature
• stress
• and hibernation.

So, its quite clear that lipids are important to animals, but how does the body actually break down lipids in order to use them?

Lipids are stored as triacylglycerols (TAGs). One TAG molecule is converted to three non-esterified fatty acid molecules (NEFAs, see this post) and one glycerol molecule through the process of lipolysis which is catalysed by the enzyme lipase. An example of a triacylglycerol is shown below:

An Example of a Triaylglycerol

The reverse of lipolysis is called esterification and involves the conversion of 3 NEFAs and 1 glycerol molecule into a TAG molecule. Lipolysis occurs in two main areas in the body: in adipose tissue and in blood capillaries.

Lipolysis in Adipose Tissue:

Firstly, a hormone binds to a hormone receptor located on the surface of the cell. The hormone could be glucagon, adrenaline, growth hormone, adrenocorticotropic hormone or prolactin. This causes adenyl cyclase to convert ATP to cAMP. cAMP binds to cAMP dependent protein kinase which phosphoyrlates and activates hormone sensitive lipase. Lipase then catalyses the conversion of TAG to 3NEFAs and glycerol, as discussed earlier.

Lipolysis in Capillaries:

TAG molecules in the blood undergo lipolysis in the capillaries to deliver NEFAs to the tissues. However, because lipids are hydrophobic they can't dissolve easily in the blood plasma and so they need to be carried by lipoproteins. Lipoproteins are small spherical particles which solubilise lipids. Their structure is shown below:

Structure of a Lipoprotein
Source

There are four classes of lipoproteins, which are classed by their density. (In order from least dense to most dense)

1. Chylomicrons: these carry lipids from the gut
2. Very Low Density Lipoproteins: carry lipids from the liver
3. Low Density Lipoprotein
4. High Density Lipoprotein

The first two mainly carry TAG molecules while the last two categories primarily carry cholesterol.

Many tissues, except the liver, have the enzyme lipoprotein lipase on the surface of their capillary epithelium. As the chylomicron or very low density lipoprotein pass the enzyme it binds to lipoprotein lipase and the TAG is cleaved into NEFAs and glycerol. The NEFAs can then pass into the tissue which is nourished by the capillary. Insulin stimulates lipoprotein lipase.

So in summary, lypolysis is the main regulator for the storage of fat; it occurs in adipose tissue and capillaries and these two sites of lypolysis are different in terms of regulation and mechanism. However, the overall result is the same, that is the delivery of NEFAs into the blood for use by tissues. 

Activation and Transport into the Mitochondrion.

Lypolysis involved the conversion of a TAG molecule into 3 NEFAs and 1 glycerol. Now that NEFAs have been produced they need to be carried into the mitochondrion so they can be oxidized. Before this can occur, the NEFA is converted to its active form,  NEFACoA according to the equation:

NEFA + ATP +CoA → NEFACoA + AMP + PPi

Once this has occured, the NEFACoA is transported accross the mitochondrial membrane by a molecule called carnitine according to the following pathway:

A note on nomenclature: different textbooks or sources often use several words which mean the same thing. A NEFA is another word for Acyl or free fatty acid (FFA).

In the diagram above AcylCoA and carnitine are converted to Acylcarnitine and this is catalysed by CPT1. This can be transfered to the mitochondrial matrix by translocase. Acylcarnitine and CoA are then converted to AcylCoA and carnitine by CPT2. This AcylCoA from this reaction can then be fed into β-Oxidation. The active form of carnitine is known as L-carnitine. The inactive form is called D-carnitine.

Once the AcylCoA has been transported inside the mitochondrion it can be fed into β-Oxidation. This pathway removes 2 carbons from the AcylCoA at each step to release AcetylCoA as well as NADH and FADH. These steps repeat until the fatty acid is completely broken down.

That's all for this post, if you have any questions please feel free to ask :)