Fatty Acid Oxidation And Beta Oxidation of Fatty Acids

Fatty acid oxidation is the most important pathway of myocardial energy production, and alteration of the fatty acid beta oxidation could be a sensitive marker of ischemia & myocardial damage.

What is Fatty Acid Oxidation?

Breakdown of fats yields fatty acids and glycerol. Glycerol may be readily converted to DHAP for oxidation in synthesis or glycolysis into glucose in gluconeogenesis. Therefore, Fatty acids are broken down into two-carbon units of acetyl-CoA. To be oxidized, they need to be transported through the cytoplasm connected to coenzyme A and moved into mitochondria.

Furthermore, The latter step needs the removal of the CoA and attachment of the fatty acid to a molecule of carnitine. The carnitine complex is transported across the inner membrane of the mitochondrion when the fatty acid is reattached to coenzyme A within the mitochondrial matrix.

The process of fatty acid oxidation is called the Beta oxidation, is fairly very simple. The reactions all occur between carbons 2 and 3 and sequentially include the following:

• Dehydrogenation to create FADH2 and a fatty acyl group with a double bond in the trans configuration;
• Hydration across the double bond to put a hydroxyl group on carbon 3 in the L configuration;
• Oxidation of the hydroxyl group to make a ketone; and
• Thiolytic cleavage to release acetyl-CoA and a fatty acid two (2) carbons shorter than the beginning one.

Unsaturated fatty acids complicate the picture a bit, primarily because they have cis bonds, for the most part, if they are of biological origin and these must be converted to the relevant trans intermediate made in step 1.

Sometimes the bond must be moved down the chain, as well, in order to be positioned properly. Two enzymes (described below) handle all the necessary isomerizations and moves necessary to oxidize all of the unsaturated fatty acids.

Regulation of Mitochondrial Fatty Acid Oxidation

The rate of fatty acid oxidation changes in response to the hormonal and nutritional state of the animal. The rate of fatty acid oxidation is high during fasting but low within the fed animal.

One cause for this modification is the higher concentration of unesterified (free) fatty acids within the circulation of the fasting animal as compared with the concentration in the fed animal.

Furthermore, an increased concentration of free fatty acids results in higher rates of the cellular uptake and oxidation of fatty acids. In the liver, which has high capacities for each synthesizing and oxidizing fatty acids, a reciprocal relationship exists between these two processes. when feeding, once carbohydrates are converted to triacylglycerols, the rate of fatty acid synthesis is high as a result of acetyl-CoA carboxylase is active.

This enzyme catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, therefore, the 1st committed intermediate in fatty acid synthesis. Malonyl-CoA binds to and effectively inhibits CPT I that initiates the uptake of fatty acids by mitochondria.

Therefore, when fatty acids are rapidly synthesized, the cytosolic concentration of malonyl-CoA is high, and also the mitochondrial uptake and oxidation of fatty acids are inhibited.

furthermore, These situation is reversed during fasting when lower blood glucose levels cause the plasma concentration of the hormone glucagon to extend which of insulin to decrease. Glucagon promotes the phosphorylation and inactivation of acetyl-CoA carboxylase with the result that the cytosolic concentration of malonyl-CoA declines.

The lower concentration of malonyl-CoA causes fatty acid synthesis to decrease and fatty acid oxidation to increase or extend. The identical regulatory mechanism could also be effective in tissues like the heart and skeletal muscle that oxidize fatty acids however don’t synthesize them.

Although malonyl-CoA is generated in these tissues by acetyl-CoA carboxylase, it looks to be metabolized by decarboxylation catalyzed by malonyl-CoA decarboxylase.

Fatty Acid Metabolism

Therefore, Fatty acid metabolism consists of catabolic processes that generate energy and anabolic processes that make biologically important molecules (phospholipids, triglycerides, second messengers, ketone bodies, and local hormones). Fatty acids are a family of molecules and these are classified within the lipid macronutrient class.

Therefore, One important role of fatty acids in animal metabolism is energy production, and its captured in the form of adenosine triphosphate (ATP). Fatty acids (mainly in the form of triglycerides) are therefore the foremost storage form of fuel in almost animals, and to a lesser extent in plants.

Furthermore, In addition, fatty acids are important components of the phospholipids that form the phospholipid bilayers out of that all the membranes of the cell are constructed (the plasma membrane and different membranes that enclose all the organelles among the cells, like as the nucleus, the mitochondria, the endoplasmic reticulum, and also the Golgi apparatus). When compared to other macronutrient classes (protein and carbohydrates), fatty acids yield the most.

ATP on an energy per gram basis, furthermore, when they are fully oxidized to CO2 and water by beta-oxidation and the citric acid cycle. Fatty acids may be also be cleaved, or partially cleaved, from their chemical attachments within the cell membrane to form second messengers among the cell, and local hormones within the immediate vicinity of the cell. The prostaglandins made up of arachidonic acid hold in the cell membrane, are likely the most well-known group of these local hormones.

Beta Oxidation of Fatty Acids

Furthermore, Fatty acid oxidation is that the mitochondrial aerobic method of breaking down fatty acid into acetyl-CoA units. Fatty acids move during this pathway as CoA derivatives utilizing NAD and FAD. Fatty acids are activated before the oxidation, utilizing ATP within the presence of CoA-SH and acyl-CoA synthetase.

Therefore, Long-chain acyl-CoA enters mitochondria guaranteed or bound to carnitine. Inside beta-oxidation, mitochondria of fatty acids takes place in which two carbon atoms are removed within the form of acetyl-CoA from acyl-CoA at the carboxyl-terminal. The bond is broken between the second carbon/beta carbon and therefore, third carbon/gamma carbon, hence the name beta-oxidation. This method provides energy from fats.

Fatty Acid Oxidation: Enzymes of Beta Oxidation

The reactions of fatty acid oxidation are notable in mirroring the oxidations within the latter half(1/2) of the citric acid cycle – dehydrogenation of succinate to make a trans double bond, hydration across the double bond to create L-malate and oxidation of the hydroxyl to create a ketone (oxaloacetate). Two(2) of the enzymes of beta-oxidation are notable.

Furthermore, the first is acyl-CoA dehydrogenase, which catalyzes the initial dehydrogenation and yields FADH2. It comes in three completely different forms – ones that work on long, medium, or short-chain length fatty acids.

furthermore, The first of those is sequestered within the peroxisome of animals whereas the others are found in the mitochondria.

Furthermore, the Plants and yeast perform Beta Oxidation exclusively in the peroxisome. the interest of the acyl-CoA dehydrogenases is the most one that works on medium-length fatty acids.

Therefore, This one, which is the one most typically deficient in animals, has been connected to sudden infant death syndrome.

Reactions two and three in Beta-oxidation are catalyzed by enoyl-CoA hydratase and 3-hydroxy acyl-CoA dehydrogenase, respectively. The latter reaction yields an NADH.
Therefore, there are the final enzyme of beta-oxidation is thiolase and this enzyme is notable in not only catalyzing the formation of acetyl-CoAs in the Beta oxidation but therefore, it also catalyzing the joining of two acetyl-CoAs to form acetoacetyl-CoA– essential for the pathways of ketone body synthesis and cholesterol biosynthesis.

Fatty Acid Oxidation Defects

FAODs ultimately impair β-oxidation of lipids within the mitochondrial matrix. The main defects that have been identified include transport of long-chain fat across the mitochondrial membrane (i.e., CPT deficiency); transport of carnitine into the cell (i.e., carnitine transporter deficiency);

The majority of defects attributed to mutations in β-oxidation directly (i.e., long-chain acyl-CoA dehydrogenase (LCAD), medium-chain acyl-CoA dehydrogenase (MCAD), and trifunctional protein (TFP) deficiencies).

Furthermore, these disorders are inherited with an autosomal recessive inheritance pattern. The more severe variants present in infancy or childhood with a primary liver or encephalopathic picture, while the adult-onset forms are predominantly myopathic.

Therefore, the main FAODs presenting in adulthood include CPT 2(II), TFP, and very-long-chain acyl-CoA dehydrogenase deficiencies.

Beta Oxidation

Beta-oxidation consists of four(4) steps:
1) Dehydrogenation catalyzed by acyl-CoA dehydrogenase, which removes two(2) hydrogens between carbons 2 and 3.
2) Hydration catalyzed by enoyl-CoA hydratase, that adds the water across the double bond.
3) The dehydrogenation catalyzed by 3-hydroxy acyl-CoA dehydrogenase, which generates NADH.
4) Thiolytic cleavage catalyzed beta-ketothiolase, which cleaves the terminal acetyl-CoA group and forms a brand new acyl-CoA which is two(2) carbons shorter than the previous one. the shortened acyl-CoA then reenters the beta-oxidation pathway.