Fatty acids as a fuel molecule Flashcards
What are fatty acids?
Fatty acids are the preferred fuel for most of the tissues in the body
Fat is the primary energy reserve in mammals
We can make TAGs to store fats
5-25% of a healthy body weight can be stored fat
Excess energy consumed as glucose is stored as fat, excess energy from food turns into fat
Why store fuel as fats?
Fatty acids are more reduced than carbohydrates (more energy released when oxidised in pathways). The carbon in fatty acids are more reduced hence they’re storing more energy as it can be oxidised more before becoming CO2.
Stored carbohydrate (glycogen) is approx 2/3 water, glucose is a polar molecule whereas fatty acids are non-polar molecules meaning when you store them you do not need a lot of water (as water is polar)
How are fats delivered to blood?
When we want to take our fat out of storage signals activate a lipase enzyme that chops the fatty acids off of the glycerol. The concentration of glycerol and FFA increase allowing them to passively diffuses into the blood, glycerol goes into the liver.
Blood is mainly main of water and FFA are non-polar, Albumin (protein) has lots of amino acids with polar side chains sticking out and hydrophobic pockets that FFA can sit in allowing FFA to move around in blood via being carried by albumin
How are fats delivered from blood to tissue?
In tissues concentration of fuel molecules are low, FFA can passively diffuse out of the tissue into cell
Cytosol of a cell is a polar environment hence FABP-FFA binds to FFA inside the ‘barrel’ formed by beta-sheets and can carry FFA into cell
How are fatty acids activated?
Fatty acids are activated before B-oxidation. This occurs before the fatty acid enters the mitochondria. Fatty acids are activated by attachment to CoA to make fatty acyl-CoA. Energy is needed to add CoA hence it is coupled with hydrolysis of ATP to AMP (adenine monophosphate)
How are fatty acids moved through the outer membrane of mitochondria?
To move activated fatty acid out of cytosol into mitochondrial matrix we need to cross through two membranes (outer and inner)
In the outer membrane we have a fatty acyl CoA carrier that can pass fatty acyl-CoA through the outer membrane
How are fatty acids moved through the inner membrane of mitochondria?
The inner membrane requires the conversion to fatty acyl-carnitine.
Carnitine acyltransferase transfers acyl group and a carnitine, replaces CoA from fatty acyl-CoA with a carnitine to form fatty acyl-carnitine (reversible reaction) which can diffuse through a carrier protein in the inner membrane hence fatty acid can enter the mitochondrial matrix
Need to reverse reaction between carnitine and CoA to revert fatty acyl-carnitine into the correct form fatty acyl-CoA to be used in the mitochondrial matrix
What is beta-oxidation?
B-oxidation uses fatty acids with an even number of carbons that are saturated (no double bonds)
No ATP is directly made however energy that is released is transferred to the coenzymes NAD and FAD
The carbon chain is cut into 2 carbon pieces. The product of B-oxidation, acetyl-CoA is further oxidised in the citric acid cycle
What are the first three reactions in B-oxidation?
Take fatty acyl-CoA, chop off two subunits and capture energy
In the first three reactions there is a rearrangement
In the first reaction we are going from a single bond to a double bond, oxidation reaction of fatty acyl-CoA meaning something must be oxidised = FAD -> FADH2
In the second reaction hydration occurs (water is added to the molecule)
In the third reaction oxidation occurs hence NAD+ is reduced to NADH and an H+
What happens in the 4th reaction in beta-oxidation?
In reaction 4 enzyme, thiolase cleaves/chops between the alpha and beta carbons
In this reaction actyl-CoA is released
The CoA-SH is added to the carbon chain forming a product of fatty acyl-CoA which is two carbons shorter
If you attach CoA you require energy which is sourced from cleaving between the alpha and beta carbons
What are the products of beta-oxidation?
In each round of beta oxidation we get 1 NADH, 1 FADH2 and 1 acetyl-CoA
In each round of beta oxidation we chop off two carbons, the last two carbons don’t go through beta oxidation, for example if we have 16 carbons we only go through beta oxidation 7 times (no of carbons divided by 2 minus 1) so we create 7NADH, 7FADH2 and 8 acetyl CoA
