Fatty acid degradation is the process in which

fatty acids In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

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 oxidation, o ...

, the entry molecule for the

citric acid cycle The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...

, 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. The breakdown of this fat is known as

lipolysis Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolysis, hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in Adipose tissue, fat adip ...

. The products of lipolysis,

free fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...

s, are released into the bloodstream and circulate throughout the body. During the breakdown of

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

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 us ...

, 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 Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

nucleophilic attack In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they a ...

on the α-phosphate of ATP to form

pyrophosphate In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate () and tetrasodium pyrophosphate (), among others. Often pyrophosphates a ...

and an acyl chain linked to AMP. The next step is formation of an activated

thioester In organic chemistry, thioesters are organosulfur compounds with the molecular structure . They are analogous to carboxylate esters () with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix ...

bond between the fatty acyl chain and

Coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric ac ...

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 is transported into the

mitochondrial matrix In the mitochondrion, the matrix is the space within the inner membrane. It can also be referred as the mitochondrial fluid. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitoc ...

. 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 from the cytosol into mitochondria to be oxidized for f ...

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

translocase Translocase is a general term for a protein that assists in moving another molecule, usually across a cell membrane. These Enzyme, enzymes catalyze the movement of ions or molecules across membranes or their separation within membranes. The reactio ...

# Acyl carnitine (such as Palmitoylcarnitine) is converted to acyl CoA by ''carnitine acyltransferase (palmitoyltransferase) II'' located on the inner mitochondrial membrane. The liberated carnitine returns to the cytosol. ''Carnitine acyltransferase I'' undergoes

allosteric In the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the p ...

inhibition as a result of malonyl-CoA, an intermediate in fatty acid biosynthesis, in order to prevent futile cycling between

beta-oxidation In biochemistry and metabolism, beta oxidation (also β-oxidation) is the Catabolism, 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. Acetyl ...

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. Two ''De novo synthesis, de novo'' fatty acid syntheses can be distinguished: cytosolic fatty acid synthesis (FAS/FASI) ...

. 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—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...

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 which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...

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

FAD A fad, trend, or craze is any form of collective behavior that develops within a culture, a generation, or social group in which a group of people enthusiastically follow an impulse for a short time period. Fads are objects or behaviors tha ...

# Hydration #

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