Module 8 - Fatty Acid Degredation Flashcards
β-oxidation
the process whereby fatty acids are degraded to acetyl CoA, NADH and FADH2
Carnitine
a biomolecule to which fatty acids are attached which facilitates their transport into the mitochondrial matrix for oxidation.
Hormone-Sensitive Lipase
an enzyme in adipose that is activated by hormone-stimulated cAMP signalling system, through covalent phosphorylation of the enzyme.
Ketone Bodies
water-soluble biomolecules that are formed in the liver from acetyl CoA and which can be used by various tissues as an energy source.
Fatty acids are degraded by a process called β-oxidation.
This is a repetitive process whereby long-chain fatty acids are sequentially degraded to acetyl CoA, depending on the length of the fatty acid.
What is the structure of a fatty acid?
a long hydrocarbon chain with a carboxylic acid group on the end, thus the name “fatty acid”
The length of fatty acids varies, with commonly occurring ones ranging from 12-20 carbons in length
The hydrocarbon chains, which are very non-polar in nature, can be fully reduced (consisting of (-CH2)n) or can have some double bonds
Most double bonds in fatty acids are in the cis-configuration, which means that the substituents on each side of the double bond are on the same side.
This induces a kink in the hydrocarbon chain, which affects their physical properties such as lowering the melting point of the fatty acid.
How are fatty acids stored?
as triacylglycerol, a neutral lipid, in adipose tissue
What is visceral adipose tissue?
fat that accumulates in the abdomen around heart, liver and intestine in obese individuals
Why is adipose tissue necessary?
it stores an important fuel
it secretes small biomolecules called “adipokines” which control overall body metabolism and appetite.
How are fatty acids used in the body as fuel?
they have to be cleaved off of triacylglycerol (or mobilized) by an enzyme called lipase, and then released into the blood
What is the first stage of fatty acid degradation?
Mobilization of Fatty Acids from Triacylglycerol in Adipose Tissue
How is Triacylglycerol (also called triglyceride) in adipose broken down by the action of several lipases into glycerol and three fatty acids?
a hydrolysis reaction, and three water molecules are used to cleave off the three fatty acid residues
There are 3 different lipases involved in breaking down triglycerol.
The enzymes that cleave off the first two fatty acids, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HS-lipase), are regulated by hormones that signal a need for more fuel.
MAG Lipase is the third lipase that acts on monoacylglycerol to release the third fatty acid.
ATGL and HS-lipase are regulated by which hormones?
epinephrine and glucagon
How do epinephrine and glucagon activate the enzymes?
bind to their respective receptor on the surface of adipose cells, and activate the cAMP signalling system
cAMP activates protein kinase A, which activates ATGL and HS-lipase
This control system ensures that triacylglycerol is degraded only when the body is low on energy supply.
What happens when the fatty acid degradation from the first step is complete?
the fatty acids and glycerol are both released into the blood.
Fatty acids are water-insoluble, and are transported in the blood bound to the blood protein albumin.
fatty acids go to many tissues in the body where they are used as fuel
glycerol is taken up by the liver, where it is converted to dihydroxyacetone phosphate
Diagram of the fate of glycerol and fatty acids after the first step.
activated fatty acids are still not able to be transported across the inner mitochondrial membrane.
At the surface of the inner mitochondrial membrane, on the cytoplasmic side, the acyl group of Acyl CoA gets transferred to a biomolecule called carnitine, forming acyl carnitine.
The enzyme catalyzing this reaction is called Carnitine acyltransferase I.
Acyl carnitine is able to be transported across the inner mitochondrial by a specific translocase
Once inside the mitochondria, the reverse reaction from that shown above is catalyzed by Carnitine acyltransferase II, which reconstitutes acyl CoA and releases free carnitine.
Carnitine is shuttled back into the cytosol so it can be re-esterified to another fatty acid to assist in bringing it into the mitochondria.
During the third stage, The fatty acyl CoA is now in the mitochondrial matrix where it can undergo β-oxidation. How many reactions are involved with β-oxidation?
4
What is the first step of β-oxidation?
Enzyme - Acyl CoA dehydrogenase
the bond between the α and β carbons (in red) becomes oxidized to a double bond, and the electrons are used to reduce FAD to FADH2.
FADH2 can then donate its electrons to the electron transport chain to produce ATP
What is the second step of β-oxidation?
In this hydration reaction, water is added across the double bond, which puts an –OH on the β-carbon, and a hydrogen on the α-carbon.
The product is 3-hydroxyacyl CoA since the hydroxyl is on the number 3, or β, carbon.
What is the third step of β-oxidation?
Enzyme – β-hydroxyacyl CoA dehydrogenase
In this oxidation reaction, 3-hydroxyacyl CoA is oxidized to form 3-ketoacyl CoA and NAD+ becomes reduced.
Note that the β-carbon now is fully oxidized, having started out as a CH2 and is now a C=O.
The NADH produced can donate its electrons to the electron transport chain.
What is the fourth step of β-oxidation?
Enzyme – Thiolase or 3-ketoacyl thiolase
a two-carbon unit is cleaved off the end of the 3-ketoacyl CoA, which is an acetyl CoA unit.
This cleavage is achieved using free CoA, with the –SH group attacking the bond between the α and β-carbon.
This gives the second product, acyl CoA, which is two carbons shorter than what was started with.
This now goes through the four reactions above again, releasing yet another acetyl CoA. When the acyl CoA is degraded to a four-carbon unit, the final round of β-oxidation releases two acetyl CoA and completes the β-oxidation.
