Biosynthesis of fatty acids and beta oxidation

Synthesis of fatty acids and beta oxidation of fatty acids

1. FATTY ACID SYNTHESIS AND BETA OXIDATION OF FATTY ACIDS SUBMITTED BY B.MOURIAN 23BOTA14

2. Fatty acids are organic molecules characterized by a long hydrocarbon chain and a terminal carboxyl group (-COOH). They are the building blocks of fats and oils, which are types of lipids. Fatty acids can vary in chain length, degree of saturation, and the position of double bonds. FATTY ACIDS

3. Steps Of Fatty Acid Biosynthesis Transportation of Acetyl CoA. Formation of Malonyl CoA. First round of Fatty Acid Biosynthesis:- A. Activation of Acetyl group. B. Activation of Malonyl group. Fatty Acid biosynthesis. Chain Elongation .

4. Transportation of Acetyl CoA Nearly all acetyl-CoA used in fatty acid synthesis is formed in mitochondria. Acetyl co A has to move out to cytosol. Intra-mitochondrial acetyl-CoA first reacts with oxaloacetate to form citrate, in the TCA cycle. Citrate then passes into the cytosol by Citrate Transporter. In the cytosol, citrate is cleaved by citrate lyase regenerating acetyl-CoA .

5. Formation of Malonyl CoA ATP dependent reaction. The reaction takes place in two steps: carboxylation of biotin (involving ATP) and transfer of the carboxyl to acetyl-CoA to form malonyl-CoA. This reaction is catalyzed by Acetyl co A carboxylase. The overall reaction, which is spontaneous, may be summarized as: HCO3- + ATP + acetyl-CoA ADP + Pi + malonyl-CoA

6. First round of Fatty Acid Biosynthesis A) Activation of Acetyl group The acetyl group from acetyl-CoA is transferred to the Cys -SH group of the ketoacyl ACP synthase. This reaction is catalyzed by acetyl CoA transacetylase. B) Activation of Malonyl group Transfer of the malonyl group to the – SH group of the ACP is catalyzed by malonyl- CA ACP transferase.

7. FATTY ACID SYNTHESIS After activation, the processes involved are Step 1: Condensation Step 2: Reduction Step 3: Dehydration Step 4: Reduction

8. Transfer of the growing FA chain Growing fatty acid chain is transferred from the acyl carrier protein (ACP) to Cys SH group. This reaction makes way for the next incoming malonyl group. The enzyme involved is acetyl- CoA transacetylase. Beginning of second round of FA Biosynthesis . The butyryl group is on the Cys -SH group. The incoming malonyl group is first attaches to ACP. In the condensation step, the entire butyryl group is exchanged for the carboxyl group on the malonyl residue.

9. Chain Elongation A new malonyl-CoA molecule combines with the —SH of 4'- phosphopantetheine , displacing the saturated acyl residue onto the free cysteine —SH group. The sequence of reactions are repeated until a saturated 16-carbon acyl radical (Palmityl) has been assembled. Catalyzed by enzyme Thioesterase ( deacylase ). Result of fatty acid synthesis activity Seven cycles of condensation and reduction produce the 16-carbon saturated palmitoyl group, still bound to ACP. Chain elongation usually stops at this point, and free palmitate is released from the ACP molecule. Smaller amounts of longer fatty acids such as stearate (18:0) are also formed.

10. FATTY ACID ELONGATION Palmitate in animal cells is the precursor of other long chained FAs. By further fatty acid chain length is elongated through the action of FA elongation systems present in the smooth endoplasmic reticulum and the mitochondria. Regulation of Fatty acid biosynthesis The reaction catalyzed by acetyl- CoA carboxylase is the rate limiting step in the biosynthesis of fatty acids. Long-chain fatty acid synthesis is controlled in the short term by allosteric and covalent modification of enzymes and in the long term by changes in gene expression.

11. OXIDATION OF FATTY ACIDS Fatty acid oxidation, also known as beta-oxidation , is a metabolic process that breaks down fatty acids into acetyl-CoA molecules, which enter the citric acid cycle to generate energy. This process primarily occurs in the mitochondria. Fatty acid oxidation is initiated on the outer mitochondrial membrane. There the fatty acids, which like carbohydrates are relatively inert, must first be activated by conversion to an energy-rich fatty acid derivative of coenzyme A called  fatty acyl-coenzyme A   (CoA). The activation is catalyzed by  acyl-CoA synthetase .

12. TYPES Beta oxidation:   It is the major mechanism of oxidation of fatty acids that occurs in mitochondria and peroxisomes . It releases acetyl CoA by breaking the carbon chain between C2 and C3. Alpha oxidation :   It is a minor oxidation pathway that occurs in  peroxisomes . The chain is broken between C1 and C2 and releases CO 2  per cycle. Omega oxidation :   It is another minor oxidation pathway that occurs in the endoplasmic reticulum . The action site for this type of reaction is the methyl end of the molecule.

13. STEPS INVOLED IN FATTY OXIDATION Activation of Fatty Acids Location: Cytosol Process: Fatty acids are activated by attaching to coenzyme A (CoA) to form acyl-CoA. This reaction requires energy in the form of ATP, which is converted to AMP and pyrophosphate ( PPi ). The enzyme acyl-CoA synthetase catalyzes this reaction. Transport into the Mitochondrial Location: Mitochondrial membrane Process: Acyl-CoA cannot directly cross the mitochondrial membrane. It combines with carnitine to form acylcarnitine , which is transported into the mitochondrial matrix. Inside the mitochondria, acylcarnitine is converted back to acyl-CoA, and carnitine is recycled. The enzyme carnitine palmitoyltransferase I (CPT I) catalyzes the formation of acylcarnitine, and carnitine palmitoyltransferase II (CPT II) catalyzes the formation of acyl-CoA inside the mitochondria.

14. Beta-Oxidation Location : Mitochondrial matrix Process Acyl-CoA undergoes a series of four reactions that repeatedly shorten the fatty acyl chain by two carbon atoms at a time, producing acetyl-CoA. Dehydrogenation : A double bond is formed between the alpha and beta carbons of the fatty acyl chain by the enzyme acyl-CoA dehydrogenase. FAD is reduced to FADH2 in this step.

15. Hydration Water is added to the double bond, forming a hydroxyl group at the beta carbon. The enzyme enoyl-CoA hydratase catalyzes this reaction . Dehydrogenation The hydroxyl group at the beta carbon is oxidized to a keto group by the enzyme beta- hydroxyacyl -CoA dehydrogenase. NAD+ is reduced to NADH in this step. Thiolysis The beta-ketoacyl-CoA is cleaved between the alpha and beta carbons by the enzyme acyl-CoA acetyltransferase ( thiolase ), releasing acetyl-CoA and a new acyl-CoA that is two carbons shorter

16. Entry of Acetyl-CoA into the Citric Acid Cycle Location : Mitochondrial matrix Process The acetyl-CoA produced in beta-oxidation enters the citric acid cycle, where it is completely oxidized to CO2 and H2O, generating ATP through oxidative phosphorylation. Energy Yield from Fatty Acid OxidationThe number of ATP molecules produced from fatty acid oxidation depends on the length of the fatty acid chain. For example, the complete oxidation of palmitic acid (a 16-carbon fatty acid) yields 106 ATP molecules.  

17. REGULATION OF BETA OXIDATION Oxidation Fatty acid oxidation is regulated by various factors, including: Hormones : Glucagon and epinephrine stimulate fatty acid oxidation, while insulin inhibits it. Energy levels : When the body's energy needs are high, fatty acid oxidation is increased. Availability of oxygen: Fatty acid oxidation requires oxygen.

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