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<p style="text-align: justify;">It is the process of conversion of large aliphatic lipid molecules to simple acyl units. These units are processed through a citric acid cycle and produce energy. Fatty acids are stored in adipocytes which are degraded under the action of the lipase enzyme.</p>
<p style="text-align: justify;">Free fatty acids are released in the bloodstream in which bind with the albumin protein. This protein maximizes its solubility. The absence of this protein in blood is termed albumin. Brain and erythrocytes cant use fatty acids directly so they rely on glucose during fasting.</p>
<h2 style="text-align: justify;"><span style="color: #236fa1;">1. Steps of fatty acid oxidation -</span></h2>
<h3><span style="color: #236fa1;">1.1 Activation of Fatty acid :</span></h3>
<p style="text-align: justify;">It is activated by the addition of coenzyme A (CoA) to the fatty acid. This reaction is catalyzed by acyl CoA synthetase in which the energy is stored in the thioester bond.</p>
<p style="text-align: center;">Fatty acid + CoA + ATP&nbsp; &nbsp; &nbsp; <span style="color: #202124; font-family: arial, sans-serif; font-size: 14px; text-align: left; background-color: #ffffff;">&rarr;&nbsp; &nbsp;</span>&nbsp;acyl-CoA + AMP + PPi</p>
<h3 style="text-align: left;"><span style="color: #236fa1;">1.2 Transport across the membrane :</span></h3>
<p style="text-align: justify;">The activation of fatty acid occurs in the cytosol whereas oxidation of fatty acid occurs inside the mitochondrial matrix. So it is compulsory for the fatty acid to transport across the mitochondrial membrane. So this activity is done by a carrier protein named carnitine. Carnitine is synthesized from lysine and methionine in the liver. The reaction of fatty acyl CoA with carnitine is shown below -</p>
<p><img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/Transport_of_fatty_acid_across_the_membrane_10d180818e.PNG" alt="Transport of fatty acid across the membrane" /></p>
<p style="text-align: center;">Fig.: Transport of fatty acid across the membrane</p>
<p style="text-align: justify;">Carnitine acyltransferase is inhibited by the malonyl CoA and prevents the entry of fatty acids into mitochondria. Insulin also inhibits this transport by activating acetyl CoA carboxylase (fatty acid synthesis) and increasing the malonyl CoA concentration in the cytoplasm.</p>
<h2 style="text-align: justify;"><span style="color: #236fa1;">2.&nbsp;<strong><span style="font-family: 'Noto Sans', Helvetica, Arial, sans-serif; font-size: 16px; text-align: start; background-color: #ffffff;">&beta; - </span></strong>oxidation of fatty acid -</span></h2>
<p style="text-align: justify;">After entry into the mitochondrial matrix, fatty acyl is degraded in the steps of b oxidation by flavin adenine dinucleotide (FAD), hydration, oxidation by NAD<sup>+</sup>, and thiolysis by CoA. This reaction occurs at the b position of carbon</p>
<p style="text-align: justify;">that's why it is named oxidation. The brief reaction of the fatty acid oxidation are-</p>
<p style="text-align: justify;">&bull; Dehydrogenation &ndash; this reaction is catalyzed by acyl CoA dehydrogenase which catalyzes the removal of two hydrogen atoms.</p>
<p style="text-align: justify;">&bull; Hydration &ndash; one molecule of water is added and reaction catalyzed by enoyl CoA hydratase.</p>
<p style="text-align: justify;">&bull; Dehydrogenation &ndash; Again removal of two H atoms by 3&ndash;hydroxy acyl dehydrogenase.</p>
<p style="text-align: justify;">&bull; Thiolysis &ndash; CoA SH is added to the molecule and the reaction is catalyzed by thioesterase which breaks the SH bond and releases one molecule of acetyl CoA and the rest of the molecule gets back to an oxidation process.&nbsp;</p>
<p><img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/Steps_of_b_oxidation_of_fatty_acid_4fb6663c0b.PNG" alt="Steps of b-oxidation of fatty acid" /></p>
<p style="text-align: center;">Fig.: Steps of <span style="color: #282828; font-family: 'Noto Sans', Helvetica, Arial, sans-serif; font-size: 16px; text-align: start; background-color: #ffffff;">&beta;</span>-oxidation of fatty acid</p>
<h3 style="text-align: left;"><span style="color: #236fa1;">The overall reaction of a fatty acid molecule -&nbsp;</span></h3>
<p><img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/1_f913a626b3.PNG" alt="" /></p>
<h3><span style="color: #236fa1;">Fate of Products</span></h3>
<p>&bull; FADH<sub>2</sub> and NADH are transported to the electron transport chain and generate ATP.</p>
<p>&bull; Acetyl CoA is transported</p>
<h2><span style="color: #236fa1;">3. Formation of ketone bodies and degradation of ketone bodies -</span></h2>
<p style="text-align: justify;">Either for the generation of more NADH<sub>2</sub> and FADH by entering into Krebs cycle and producing ATP. or transported for the generation of ketone bodies which are used by other tissues as an energy source. For the formation of ketone bodies, two molecules of Acetyl CoA are condensed into acetoacetyl CoA which is further processed and converted to&nbsp;<span style="color: #282828; font-family: 'Noto Sans', Helvetica, Arial, sans-serif; font-size: 16px; text-align: start; background-color: #ffffff;">&beta;</span>-hydroxybutyrate.&nbsp;</p>
<p><img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/Fig_Steps_of_formation_of_ketone_bodies_49dac030d1.PNG" alt="Steps of formation of ketone bodies" /></p>
<p style="text-align: center;">Fig.: Steps of formation of ketone bodies</p>
<h2 style="text-align: left;"><span style="color: #236fa1;">4. Other Fatty acid oxidation -</span></h2>
<h3><span style="color: #236fa1;">Alpha oxidation :</span></h3>
<p style="text-align: justify;">It is an alternative form of lipid oxidation. It does not require the activation of fatty acids. COOH group of lipid is decarboxylated and then this undergoes the cycle of&nbsp;<span style="color: #282828; font-family: 'Noto Sans', Helvetica, Arial, sans-serif; font-size: 16px; text-align: start; background-color: #ffffff;">&beta;</span>-oxidation.</p>
<p style="text-align: justify;">This oxidation occurs for the synthesis of an-OH fatty acid like cerebrotonic acid which constitutes cerebrosides in the brain. It oxidizes phytanic acid which is produced by dietary phytols of chlorophyll by phytate&nbsp;<span style="color: #282828; font-family: 'Noto Sans', Helvetica, Arial, sans-serif; font-size: 16px; text-align: start; background-color: #ffffff;">&alpha;</span>-oxidase and pristanic acid is oxidized by&nbsp;<span style="color: #282828; font-family: 'Noto Sans', Helvetica, Arial, sans-serif; font-size: 16px; text-align: start; background-color: #ffffff;">&beta;</span>- oxidation.</p>
<p style="text-align: justify;">A defect in oxidation causes a rare genetic disorder Refsum disease in which deficiency of phytate an oxidase enzyme.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">Omega (<span style="font-family: symbol;">w</span>) oxidation :</span></h3>
<p style="text-align: justify;">It is found in the liver and microsomes. It causes the hydroxylation of omega carbon.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">Peroxisomal fatty acid oxidation :</span></h3>
<p>It is a modified form of b oxidation in which acetyl CoA and H<sub>2</sub>O<sub>2</sub> are formed as final products. This pathway does not generate ATP. Zellweger Syndrome is the condition of absence of peroxisome in all the cells of the body so the patient is unable to oxidize long fatty acid chains of C<sub>26</sub> &ndash; C<sub>38</sub>.</p>
<h2><span style="color: #236fa1;">5. Lipid synthesis -</span></h2>
<p style="text-align: justify;">The synthesis of fatty acids is catalyzed by fatty acid synthase which is a multifunctional enzyme. This enzyme is located in the cytoplasm which acts upon the acetyl CoA as a primer molecule. NADPH is used as a reducing agent in this reaction.</p>
<p style="text-align: justify;">The fatty acid synthase enzyme catalyzes all the seven reactions of this process. It is a homodimer that contains two identical peptide chains. Every reaction is catalyzed by a specific enzyme. This enzyme has 3 domains &ndash; Domain I catalyzes the condensation of acetyl CoA and malonyl CoA, Domain II catalyzes the formation of a final product of the process and Domain III catalyzes the release of the final product.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">Steps -</span></h3>
<h3 style="text-align: justify;"><span style="color: #236fa1;">&bull; Formation of Malonyl CoA &ndash; </span></h3>
<p style="text-align: justify;">Acetyl CoA is impermeable to the mitochondrial membrane so it is converted to malonyl CoA. It is catalyzed by the enzyme acetyl CoA carboxylase. It uses Mn<sup>+2</sup> and biotin as a coactivator which donates a CO<sub>2</sub> molecule and one ATP molecule.&nbsp;</p>
<p><img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/Formation_of_Malonyl_Co_A_0dd97697cb.PNG" alt="Formation of Malonyl CoA" /></p>
<p style="text-align: center;">Fig.: Formation of Malonyl CoA</p>
<p style="text-align: justify;">&bull; Now the further process is catalyzed by the fatty acid synthase which has Cys-SH and Pan-SH as two arms of it. Both of these arms accept acetyl CoA and Malonyl CoA respectively. Both arms act as transacylase which removes CoA from both of the molecules and Acyl Carrier Protein is attached.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">&bull; Condensation &ndash; </span></h3>
<p style="text-align: justify;">As acetate attacks on malonate to form acetoacetyl ACP which is catalyzed by Keto acyl synthase. A single molecule of CO<sub>2</sub> is lost in this reaction and the acetoacetyl ACP remains attached to Pan SH.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">&bull; Reduction &ndash; </span></h3>
<p style="text-align: justify;">NADPH is converted to NADP<sup>+</sup> and the reaction is catalyzed by <span style="color: #282828; font-family: 'Noto Sans', Helvetica, Arial, sans-serif; font-size: 16px; text-align: start; background-color: #ffffff;">&beta;</span>-keto acyl reductase.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">&bull; Dehydration &ndash; </span></h3>
<p style="text-align: justify;">a single water molecule is removed by <span style="color: #282828; font-family: 'Noto Sans', Helvetica, Arial, sans-serif; font-size: 16px; text-align: start; background-color: #ffffff;">&beta;</span>-OH-butyryl dehydratase.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">&bull; Reduction &ndash; </span></h3>
<p style="text-align: justify;">NADPH is used and catalyzed by enoyl reductase.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">&bull; Thiolysis &ndash; </span></h3>
<p style="text-align: justify;">It is the final reaction of a molecule. If synthesizing lipid is to be a larger molecule then all of these steps are repeated. SH bond is cleaved by thioesterase enzyme and ACP molecule is released from the molecule and final product is released from the enzyme.</p>
<p style="text-align: justify;">For the synthesis of a 16 carbon molecule i.e. palmitic acid, the final reaction will be &ndash;&nbsp;</p>
<p><img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/1_4808e03fc4.PNG" alt="" /></p>
<p>So the overall reaction will be</p>
<p><span style="color: #236fa1;"><img style="display: block; margin-left: auto; margin-right: auto;" src="https://vediphlie-aws.s3.ap-south-1.amazonaws.com/2_b5c9ea9e95.PNG" alt="" /></span></p>
<h2><span style="color: #236fa1;">6. Regulation of fatty acid synthesis -</span></h2>
<h3><span style="color: #236fa1;">Allosteric Control :</span></h3>
<p>This is sudden or short-term control in which enzymes can be controlled by covalent modification.</p>
<h3><span style="color: #236fa1;">Hormonal Control :</span></h3>
<p>Hormones affect the enzyme and regulate the process of lipid synthesis.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">&bull; Acetyl CoA Carboxylase :</span></h3>
<p style="text-align: justify;">This enzyme catalyzes the rate-limiting step of this process. It is regulated by phosphorylation and dephosphorylation by protein kinases. Citrate acts as an activator for this enzyme.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">&bull; Glucagon :</span></h3>
<p style="text-align: justify;">It inhibits glycolysis by inactivating the PFK enzyme so thereby decrease in the synthesis of citrate in the Krebs cycle. So a decrease in citrate inactivates the acetyl CoA carboxylase and reduces fatty acid synthesis.</p>
<h3 style="text-align: justify;"><span style="color: #236fa1;">&bull; Insulin :</span></h3>
<p style="text-align: justify;">It acts in contrast to glucagon. It enhances citrate thereby activating AcetylCoA carboxylase and more lipid synthesis.</p>

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Fatty acid oxidation is the process of conversion of large aliphatic lipid molecules to simple acyl units. 

Fatty Acid Oxidation - Steps, β - Oxidation, Regulation of fatty acid synthesis 

Fatty acid oxidation is the process of conversion of large aliphatic lipid molecules to simple acyl units. In the Fatty Acid Oxidation topic of Biochemistry; we will cover Steps of fatty acid oxidation, β - oxidation of fatty acid, Formation of ketone bodies and degradation of ketone bodies,  Lipid synthesis, Regulation of fatty acid synthesis etc. 

Fatty Acid Oxidation

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