What Is Fatty Acid Degradation?

Fatty acid oxidation means that glycerol and fatty acids produced by the hydrolysis of fats can be oxidatively decomposed to produce carbon dioxide and water under conditions of sufficient oxygen supply, and release a large amount of energy for the body to use. Fatty acid oxidation in the body is most important for liver and muscle Active and extremely low in neural tissue. Fatty acid oxidation methods include -oxidation and special oxidation methods. Special oxidation methods include: propionic acid oxidation, -oxidation, omega-oxidation, and unsaturated fatty acid oxidation.

Fatty acid oxidation

- Fatty acid oxidation -oxidation

Overview

Beta-oxidation of fatty acids. Liver and muscle are the most active tissues for fatty acid oxidation. This process can be divided into three phases: activation, transfer, and -oxidation.

In the liver, beta-oxidation of fatty acids produces acetyl-CoA. Two molecules of acetyl-CoA can condense to form acetoacetic acid. Acetoacetic acid can be decarboxylated to produce acetone, and can also be reduced to form -hydroxybutyric acid. Acetoacetic acid, -hydroxybutyric acid, and acetone are collectively referred to as ketone bodies.

-oxidation premise

1> Activation of fatty acids

Like glucose, fatty acids must be activated before they can participate in metabolism. Its activated form is a thioester-fatty acyl CoA, and the enzyme that catalyzes the activation of fatty acids is acyl CoA synthetase.

The fatty acyl CoA generated after activation has enhanced polarity and is easily soluble in water; it has high-energy bonds in the molecule and is active in nature; it is a specific substrate for enzymes and has a large affinity with enzymes, so it is easier to participate in reactions.

The fatty acyl-CoA synthetase, also called thiokinase, is distributed in the cytoplasm, on the mitochondrial membrane, and on the endoplasmic reticulum membrane. Sulfokinase in the cytoplasm catalyzes the activation of short-chain fatty acids in medium; enzymes on the endoplasmic reticulum membrane activate long-chain fatty acids to produce fatty acyl-CoA, and then enter the endoplasmic reticulum for triglyceride synthesis; Long-chain fatty acyl CoA enters mitochondria into -oxidation.

2> Fatty CoA enters mitochondria

The enzyme that catalyzes -oxidation of fatty acids is in the mitochondrial matrix, but long-chain fatty acyl CoA cannot pass freely through the inner membrane of the mitochondria. To enter the mitochondrial matrix, a carrier is required. This carrier is carnitine, which is 3-hydroxy -4-Trimethylaminobutyric acid.

The long-chain fatty acyl CoA reacts with carnitine to produce coenzyme A and fatty acylcarnitine. The fatty acyl is linked to the 3-hydroxy group of carnitine through an ester bond. The enzyme that catalyzes this reaction is carnitine acyl transferase. This enzyme is found on the inner and outer sides of the mitochondrial inner membrane, and is an isoenzyme, which is called carnitine lipid acyltransferase I and carnitine lipid acyltransferase II, respectively. Enzyme I converts cytosolic fatty acyl CoA into coenzyme A and fatty acylcarnitine, which enter the mitochondrial inner membrane, while enzyme I transports carnitine in a molecular matrix to the outer and inner mitochondrial inner membrane. The enzyme located inside the inner membrane of the mitochondria converts fatty acylcarnitine into carnitine and fatty acyl CoA. Carnitine regains its carrier function, fatty acyl CoA enters the mitochondrial matrix and becomes a fatty acid -oxidase system. Substrate.

The rate of long-chain fatty acyl-CoA entering the mitochondria is regulated by carnitine lipid acyltransferase I and enzyme II. Enzyme I is inhibited by malonyl CoA and enzyme II is inhibited by insulin. Malonyl CoA is a raw material for the synthesis of fatty acids. Insulin induces the synthesis of acetyl CoA carboxylase to increase the concentration of malonyl CoA, thereby inhibiting enzyme I. It can be seen that insulin has an indirect or direct inhibitory effect on carnitine lipid acyltransferase I and enzyme II. When starvation or fasting, insulin secretion decreases, carnitine acyltransferase I and enzyme II activities increase, and long-chain fatty acids transferred enter the mitochondria for oxidative energy.

-oxidation process

The fatty acyl CoA enters oxidation in the mitochondrial matrix through a four-step reaction, namely dehydrogenation, water addition, dehydrogenation and thiolysis, to generate a molecule of acetyl CoA and a new fatty acyl CoA with two carbons less.

The first step of the dehydrogenation reaction is activated by fatty acyl CoA dehydrogenase, the auxiliary group is FAD, and fatty acyl CoA removes one hydrogen atom from each of the and carbon atoms to generate , - Oleyl acyl-CoA.

The second step of the hydration reaction is catalyzed by enoyl CoA hydratase to form -hydroxyfatty acyl CoA with L-configuration.

The third step of the dehydrogenation reaction is the dehydrogenation of -hydroxyfatty acyl CoA to -ketoacyl CoA under the catalysis of -hydroxyfatty acyl CoA dehydratase (Coenzyme is NAD +).

The fourth step of the thiolysis reaction is catalyzed by -ketothiolase, -ketoacyl CoA breaks the chain between and carbon atoms, plus a molecule of coenzyme A to generate acetyl CoA and one less two carbon atoms Of fatty acyl CoA.

The above four-step reaction is similar to the process of generating oxaloacetate from succinic acid via fumaric acid and malic acid in the TCA cycle, except that the fourth step of -oxidation is thiolysis, and the next step of oxaloacetate is condensation with acetyl CoA This produces citric acid.

After one cycle of long-chain fatty acyl CoA, the carbon chain is reduced by two carbon atoms to generate one molecule of acetyl CoA. Repeating the above cycle many times will gradually generate acetyl CoA.

It can be seen from the above that the -oxidation process of fatty acids has the following characteristics. The first step is to activate fatty acids to produce fatty acyl CoA, which is an energy-consuming process. Medium and short-chain fatty acids can be pulled straight into the mitochondria without a carrier, while long-chain fatty acyl CoA requires carnitine transport. The -oxidation reaction proceeds in the mitochondria, so red blood cells without mitochondria cannot oxidize fatty acids for energy. In the -oxidation process, FADH2 and NADH + H + are generated. These hydrogens need to be transferred to oxygen through the respiratory chain to generate water, which requires oxygen to participate. Oxidation of acetyl CoA also requires oxygen. Therefore, -oxidation is an absolutely aerobic process.

Physiological significance of fatty acid beta-oxidation Fatty acid beta-oxidation is the main pathway for fatty acid decomposition in the body. Fatty acid oxidation can supply a large amount of energy required by the body. Take the saturated fatty acid stearic acid of sixteen carbon atoms as an example. The total response is:

CH3 (CH2) 14COSCoA + 7NAD ++ 7FAD + HSCoA + 7H2O 8CH3COSCoA + 7FADH2 + 7NADH + 7H + ??

7 molecules of FADH2 provide 7 × 1.5 = 10.5 molecules of ATP, 7 molecules of NADH + H + provide 7 × 2.5 = 17.5 molecules of ATP, 8 molecules of acetyl CoA complete oxidation provide 8 × 10 = 80 molecules of ATP, so one molecule of palmitic acid is completely oxidized CO2 and H2O are formed, providing a total of 108 molecules of ATP. The activation process of palmitic acid consumes 2 molecules of ATP, so a molecule of palmitate completely oxidizes to produce 106 molecules of ATP. About 40% of the energy released during the oxidation of fatty acids is used by the body to synthesize high-energy compounds, and the remaining 60% is released in the form of heat, with a thermal efficiency of 40%, indicating that the body can effectively use the energy provided by the oxidation of fatty acids.

Beta-oxidation of fatty acids is also the process of fatty acid transformation. The length of fatty acid chains required by the body is different. Through beta-oxidation, long-chain fatty acids can be transformed into fatty acids of appropriate length for metabolism needs. Acetyl CoA produced during the -oxidation of fatty acids is a very important intermediate compound. In addition to being able to enter the tricarboxylic acid cycle for oxidation and energy supply, acetyl CoA is also a raw material for the synthesis of many important compounds, such as ketone bodies, cholesterol and steroids.

Fatty acid oxidation propionate oxidation

Odd-numbered carbon fatty acids, in addition to acetyl CoA through -oxidation, also produce a molecule of propionyl CoA. Propionyl CoA is produced during the catabolism of certain amino acids such as isoleucine, methionine and threonine, and bile acid is produced. Propionyl CoA is also produced during the process. Propionyl CoA can be transformed into succinyl CoA through carboxylation reaction and intramolecular rearrangement, which can be further oxidatively decomposed, and can also be formed into sugar through oxaloacetate. The reaction process is shown in the figure on the right.

- Fatty acid oxidation -oxidation

The process of fatty acids in microsomes catalyzed by monooxygenase and decarboxylase to produce alpha-hydroxy fatty acids or fatty acids with one less carbon atom is called alpha-oxidation of fatty acids. Long-chain fatty acids are catalyzed by monooxygenase, and ascorbic acid or tetrahydrofolate is used as a hydrogen donor to produce -hydroxy fatty acids with the participation of O2 and Fe2 +. This is an important component of cerebrosides and thiolipids, and -hydroxy fatty acids continue to be oxidized. Decarboxylation produces fatty acids with an odd number of carbon atoms. People with alpha-oxidation disorders cannot oxidize phytanic acid (3,7,11,15-tetramethylhexadecanoic acid).

- Fatty acid oxidation omega-oxidation

Omega-oxidation of fatty acids occurs in liver microsomes and is catalyzed by the addition of monooxygenase. First, the carbon atoms of fatty acids are hydroxylated to produce -carboxy fatty acids, and then aldehyde fatty acids are used to generate , -dicarboxylic acids, which are then activated at the -terminus or -terminus, enter the mitochondria, enter -oxidation, and finally produce amber Acyl CoA.

Fatty acid oxidation

About half of the fatty acids in the body are unsaturated fatty acids, and foods also contain unsaturated fatty acids. The double bonds of these unsaturated fatty acids are cis. When they enter -oxidation after activation, 3-cisenoyl CoA is formed. At this time, cis-3 trans-2 isomerase is required to catalyze the formation of 2-trans Enoleyl CoA for further reaction. 2-Transenonoyl CoA is added to water to generate D--hydroxyfatty acid CoA, which requires -hydroxyfatty acid CoA epimerase to catalyze the transformation from D-configuration to L-configuration for further processing. Deoxygenation reaction (only L--hydroxyacyl CoA can be used as a substrate for -hydroxyacyl CoA dehydrogenase).

Schematic of w-oxidation reaction of fatty acids

When unsaturated fatty acids are completely oxidized to form CO2 and H2O, they provide less ATP than saturated fatty acids with the same number of carbon atoms.

The a, w-dicarboxylic acid formed can be degraded by b-oxidation from both ends. Fatty acids below twelve carbon in animals are often degraded through the w-oxidation pathway; most fatty acids with oxygen-containing groups (hydroxyl, aldehyde or carboxyl) at the w-terminus in plants are also generated by w-oxidation, These fatty acids are often components of the stratum corneum or cell wall; some aerobic microorganisms can rapidly degrade hydrocarbons or fatty acids into water-soluble products. This degradation process first requires w-oxidation to generate dicarboxy fatty acids and then b-oxidation. Degradation, for example, certain planktonic bacteria in the ocean can degrade the floating oil on the sea surface, and its oxidation rate can be as high as 0.5 g / day / square meter.