Fatty acid degradation is the process in which

fatty acids In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an B ...

are broken down into their metabolites, in the end generating

acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...

, the entry molecule for the

citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and prot ...

, the main energy supply of living organisms, including bacteria and animals. It includes three major steps: * Lipolysis of and release from adipose tissue * Activation and transport into mitochondria * β-oxidation

Lipolysis and release

Initially in the process of degradation, fatty acids are stored in

adipocytes Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...

. The breakdown of this fat is known as lipolysis. The products of lipolysis, free fatty acids, are released into the bloodstream and circulate throughout the body. During the breakdown of

triacylglycerols A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as we ...

into fatty acids, more than 75% of the fatty acids are converted back into triacylglycerol, a natural mechanism to conserve energy, even in cases of starvation and exercise.

Activation and transport into mitochondria

Fatty acids must be activated before they can be carried into the

mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

, where fatty acid oxidation occurs. This process occurs in two steps catalyzed by the enzyme fatty acyl-CoA synthetase.

Formation of an activated thioester bond

The enzyme first catalyzes nucleophilic attack on the α-phosphate of ATP to form pyrophosphate and an acyl chain linked to AMP. The next step is formation of an activated thioester bond between the fatty acyl chain and

Coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...

The balanced equation for the above is: RCOO⁻ + CoASH + ATP → RCO-SCoA + AMP + PP_i
This two-step reaction is freely reversible and its equilibrium lies near 1. To drive the reaction forward, the reaction is coupled to a strongly exergonic hydrolysis reaction: the enzyme inorganic pyrophosphatase cleaves the pyrophosphate liberated from ATP to two phosphate ions, consuming one water molecule in the process. Thus the net reaction becomes: RCOO⁻ + CoASH + ATP → RCO-SCoA+ AMP + 2P_i

Transport into the mitochondrial matrix

The inner mitochondrial membrane is impermeable to fatty acids and a specialized carnitine carrier system operates to transport activated fatty acids from cytosol to mitochondria. Once activated, the acyl

CoA Coa may refer to: Places * Coa, County Fermanagh, a rural community in County Fermanagh, Northern Ireland * Côa River, a tributary of the Douro, Portugal ** Battle of Coa, part of the Peninsular War period of the Napoleonic Wars ** Côa Valley ...

is transported into the mitochondrial matrix. This occurs via a series of similar steps: # Acyl CoA is conjugated to

carnitine Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids into mitochondria to be oxidized for energy production, an ...

by ''

carnitine acyltransferase I Carnitine O-palmitoyltransferase (also called carnitine palmitoyltransferase) is a mitochondrial transferase enzyme () involved in the metabolism of palmitoylcarnitine into palmitoyl-CoA. A related transferase is carnitine acyltransferase. Molec ...

(palmitoyltransferase) I'' located on the outer mitochondrial membrane # Acyl carnitine is shuttled inside by a translocase # Acyl carnitine (such as

Palmitoylcarnitine Palmitoylcarnitine is an ester derivative of carnitine involved in the metabolism of fatty acids. During the tricarboxylic acid cycle (TCA), fatty acids undergo a process known as β-oxidation to produce energy in the form of ATP. β-oxidation occu ...

) is converted to acyl CoA by ''carnitine acyltransferase (palmitoyltransferase) II'' located on the inner mitochondrial membrane. The liberated carnitine returns to the cytosol. It is important to note that ''carnitine acyltransferase I'' undergoes

allosteric In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the ''allosteric sit ...

inhibition as a result of

malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Functions It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. Fatty acid biosynthesis Malonyl-CoA provides 2-carbon units to fatty acids and com ...

, an intermediate in fatty acid biosynthesis, in order to prevent futile cycling between

beta-oxidation In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, ...

and

fatty acid synthesis In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is co ...

. The mitochondrial oxidation of fatty acids takes place in three major steps: # β-oxidation occurs to convert fatty acids into 2-carbon acetyl-CoA units. # Acetyl-CoA enters into

TCA cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and prote ...

to yield generate reduced NADH and reduced FADH₂. # Reduced cofactors NADH and FADH₂ participate in the

electron transport chain An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples ...

in the mitochondria to yield ATP. There is no direct participation of the fatty acid.

β-oxidation

After activation by ATP, once inside the mitochondria, the β-oxidation of a fatty acids occurs via four recurring steps: #

Oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...

by FAD #

Hydration Hydration may refer to: * Hydrate, a substance that contains water * Hydration enthalpy, energy released through hydrating a substance * Hydration reaction, a chemical addition reaction where a hydroxyl group and proton are added to a compound * ...

by NAD⁺ # Thiolysis # Production of acyl-CoA and acetyl-CoA The final product of β-oxidation of an even-numbered fatty acid is

, the entry molecule for the

. If the fatty acid is an odd-numbered chain, the final product of β-oxidation will be propionyl-CoA. This propionyl-CoA will be converted into intermediate methylmalonyl-CoA and eventually succinyl-CoA, which also enters the TCA cycle.

References