Fatty Acid Oxidation: Unveiling the Intricacies of Cellular Energy Production

Elaine Hsuen^*
*Correspondence: Elaine Hsuen, Department of Biochemistry, University of Singapore, Medical Drive, Singapore, Email:

Introduction

In the intricate dance of cellular metabolism, fatty acid oxidation stands out as a vital choreographer, orchestrating the breakdown of fatty acids to generate energy. This biochemical process plays a pivotal role in meeting the energy demands of various tissues, especially during periods of fasting or intense physical activity. Delving into the molecular intricacies of fatty acid oxidation unveils a captivating tale of how cells meticulously extract energy from these lipid molecules. Before we embark on the journey of fatty acid oxidation, let's acquaint ourselves with the protagonists of these narrative fatty acids. Fatty acids are long hydrocarbon chains with a carboxyl group at one end. They are the building blocks of lipids, which include triglycerides, phospholipids and cholesterol esters. While triglycerides serve as a primary form of energy storage in adipose tissue, fatty acids are the primary substrates for energy production through oxidation [1].

Before fatty acids can enter the mitochondrial arena where oxidation occurs, they need to be mobilized from their storage depots. This process, known as lipolysis, involves the enzymatic breakdown of triglycerides into glycerol and fatty acids. Adipose tissue primarily houses triglycerides and lipolysis is stimulated by hormones like adrenaline and glucagon during times of energy demand. Fatty acids, once liberated, encounter a binding partner called albumin in the bloodstream, forming complexes that transport them to tissues with energy needs. Upon reaching their destination, fatty acids face another hurdle before they can fuel cellular processes the mitochondrial membrane.

Description

Mitochondria, often referred to as the powerhouse of the cell, host the stage for fatty acid oxidation. However, the mitochondrial membrane poses a barrier for fatty acids due to their hydrophobic nature. To overcome this hurdle, fatty acids undergo a series of transformations in the cytoplasm. The process of activation involves attaching a molecule called Coenzyme A (CoA) to the fatty acid, forming acyl-CoA. This reaction is catalysed by an enzyme called acyl-CoA synthetase. The resulting acyl-CoA molecule is now primed for transport into the mitochondria. The carnitine shuttle system facilitates the transport of acyl-CoA into the mitochondrial matrix. The enzyme Carnitine Palmitoyltransferase I (CPT-I) catalyses the transfer of the acyl group from CoA to carnitine, forming acylcarnitine. This acylcarnitine is transported across the mitochondrial membrane by a carnitine-acylcarnitine translocase. Once inside the mitochondria, Carnitine Palmitoyltransferase II (CPT-II) converts acylcarnitine back to acyl-CoA, ready for oxidation. With acyl-CoA now within the mitochondrial matrix, the main act of fatty acid oxidation begins—betaoxidation. This cyclic process involves the sequential removal of two-carbon units (acetyl-CoA) from the fatty acid chain. Each cycle comprises four key steps: oxidation, hydration, dehydrogenation and thiolysis [2].

The first step involves the oxidation of the fatty acid by the enzyme acyl- CoA dehydrogenase. This results in the formation of a trans-double bond between the alpha and beta carbons. The next step, catalysed by enoyl-CoA hydratase, introduces a water molecule across the double bond, creating a hydroxyl group. The third step involves the removal of hydrogen from the hydroxyl group, facilitated by the enzyme 3-hydroxyacyl-CoA dehydrogenase. The final step, catalysed by thiolase, results in the cleavage of the betaketoacyl- CoA into two molecules of acetyl-CoA. This acetyl-CoA can directly enter the Tricarboxylic Acid (TCA) cycle, a central hub in cellular metabolism. The repeated cycles of beta-oxidation progressively shorten the fatty acid chain, releasing acetyl-CoA units and generating high-energy electrons in the form of NADH and FADH₂. These electron carriers play a crucial role in the subsequent stages of energy production [3].

The high-energy electrons from fatty acid oxidation ultimately combine with molecular oxygen in the terminal step of the ETC, forming water. This coupling of fatty acid oxidation with the ETC not only generates ATP but also ensures the efficient utilization of oxygen in the cellular respiration process. The regulation of fatty acid oxidation is a finely tuned orchestra, responding to the dynamic energy needs of the cell. Hormones and intracellular signals play pivotal roles in modulating the enzymes involved in lipid metabolism. For example, insulin promotes fatty acid synthesis and storage, while glucagon and adrenaline stimulate lipolysis and fatty acid oxidation during fasting or stress. Additionally, the body exhibits remarkable adaptability to changes in nutritional status. During fasting or prolonged exercise, the rate of fatty acid oxidation increases to meet the heightened energy demands. Conversely, in the presence of ample glucose, the reliance on fatty acids for energy decreases, highlighting the body's ability to switch between different fuel sources [4].

Understanding fatty acid oxidation is not merely a journey into the intricacies of cellular metabolism but also holds significance in the context of human health. Dysregulation of lipid metabolism is implicated in various metabolic disorders, including obesity, type 2 diabetes and cardiovascular diseases. Defects in enzymes involved in fatty acid oxidation can lead to genetic disorders known as Fatty Acid Oxidation Disorders (FAODs). These conditions result in the inability to effectively metabolize fatty acids, leading to a build-up of toxic intermediates and energy deficiency. Timely diagnosis and management are crucial in mitigating the impact of FAODs on affected individuals. On the flip side, harnessing the knowledge of fatty acid oxidation has therapeutic implications. Researchers explore ways to modulate lipid metabolism to address conditions like obesity and metabolic syndrome. Targeting specific enzymes or signalling pathways involved in fatty acid oxidation presents a potential avenue for developing novel therapeutic interventions [5].

Conclusion

In the grand orchestration of cellular metabolism, fatty acid oxidation emerges as a symphony of precision and adaptability. From the mobilization of fatty acids to their meticulous choreography in the mitochondrial matrix, this biochemical dance sustains. As acetyl-CoA enters the TCA cycle, it undergoes a series of reactions that lead to the production of reducing equivalents NADH and FADH₂. These electron carriers shuttle electrons to the Electron Transport Chain (ETC) embedded in the inner mitochondrial membrane. The ETC is a cascade of protein complexes that transfer electrons along a series of redox reactions. As electrons move through the ETC, protons are pumped across the mitochondrial membrane, creating an electrochemical gradient. The culmination of this intricate dance is the generation of Adenosine Triphosphate (ATP), the universal currency of cellular energy.

Acknowledgement

None.

Conflict of Interest

There is no conflict of interest by author.

References

1. Liu, Dongyou, Mark L. Lawrence, Martin Wiedmann and Lisa Gorski, et al. "Listeria monocytogenes subgroups IIIA, IIIB and IIIC delineate genetically distinct populations with varied pathogenic potential." J Clin Microbiol 44 (2006): 4229-4233.

   Google Scholar, Crossref, Indexed at

2. De Queirós, Lívia Dias, Amanda Rejane Alves de Ávila, Andressa Vianna Botaro and Danielle Branta Lopes Chirotto, et al. "Combined isoflavones biotransformation increases the bioactive and antioxidant capacity of soymilk."Appl Microbiol Biotechnol 104 (2020): 10019-10031.

   Google Scholar, Crossref, Indexed at

3. Mead, Paul S., Laurence Slutsker, Vance Dietz and Linda F. McCaig, et al. "Food-related illness and death in the United States." Emerg Infect Dis 5 (1999): 607.

   Google Scholar, Crossref, Indexed at

4. Nightingale, K. K., R. A. Ivy, A. J. Ho and E. D. Fortes, et al. "inlA premature stop codons are common among Listeria monocytogenes isolates from foods and yield virulence-attenuated strains that confer protection against fully virulent strains." Appl Environ Microbiol 74 (2008): 6570-6583.

   Google Scholar, Crossref, Indexed at

5. Williams, C. F., G. E. Walton, L. Jiang and S. Plummer, et al. "Comparative analysis of intestinal tract models." Annu Rev Food Sci Technol 6 (2015): 329-350.

   Google Scholar, Crossref, Indexed at