29.4 Biosynthesis of Fatty Acids
3 min read•may 7, 2024
is a crucial process that builds long-chain fatty acids from smaller molecules. It happens in the of cells, mainly in the liver, fat tissue, and mammary glands. The process uses and as building blocks.
The complex is the star of the show, adding two-carbon units to grow the fatty acid chain. Key steps include condensation, reduction, dehydration, and another reduction. This cycle repeats until the fatty acid reaches its desired length, usually 16 or 18 carbons.
Fatty Acid Biosynthesis
Process of fatty acid biosynthesis
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- Creates long-chain fatty acids from smaller precursor molecules (acetyl CoA and malonyl CoA)
- Occurs in the cytosol of cells, primarily in the liver, adipose tissue, and mammary glands
- Acetyl CoA is a two-carbon molecule derived from the oxidation of glucose or the breakdown of amino acids
- Malonyl CoA is formed from acetyl CoA through the action of (ACC)
- ACC catalyzes the carboxylation of acetyl CoA, adding a carbonyl group to form the three-carbon malonyl CoA
- ACC contains as a prosthetic group, which plays a crucial role in the carboxylation reaction
- The fatty acid synthase (FAS) complex catalyzes the sequential addition of two-carbon units from malonyl CoA to a growing fatty acid chain
- Initial step transfers the acetyl group from acetyl CoA to the (ACP) of the FAS complex
- Subsequent steps condense malonyl ACP with the growing fatty acid chain, followed by reduction, dehydration, and reduction reactions to form the saturated fatty acid product ()
- The transports acetyl CoA from mitochondria to the cytosol for fatty acid synthesis
Key reactions in fatty acid synthesis
- Condensation: (KS) catalyzes the formation of a carbon-carbon bond between the malonyl group and the growing fatty acid, releasing CO2 and forming a -ketoacyl ACP intermediate
- Reduction: -ketoacyl ACP is reduced to -hydroxyacyl ACP by (KR) using as a reducing agent
- Dehydration: -hydroxyacyl ACP undergoes dehydration catalyzed by (DH), removing a water molecule and creating a double bond between the and carbons to form an enoyl ACP intermediate
- Reduction: Enoyl ACP is reduced to a saturated acyl ACP by (ER) using NADPH, converting the double bond to a single bond and completing the addition of the two-carbon unit to the growing fatty acid chain
- The elongation cycle repeats, with the acyl ACP serving as the substrate for the next round of condensation with malonyl ACP until the desired fatty acid length is reached (typically 16 or 18 carbons)
- releases the completed fatty acid from the FAS complex
Fatty acid biosynthesis vs beta-oxidation
- Fatty acid biosynthesis builds up fatty acids, while breaks them down
- Carriers:
- Biosynthesis uses acyl carrier protein (ACP) to transport the growing fatty acid chain
- Beta-oxidation uses (CoA) to transport the fatty acid during breakdown
- Intermediates:
- Biosynthesis uses malonyl CoA as the key intermediate, providing two-carbon units for chain elongation
- Beta-oxidation uses acyl CoA as the main intermediate, undergoing oxidation reactions to release two-carbon acetyl CoA units
- Coenzymes:
- Biosynthesis uses NADPH as the primary reducing agent in reduction steps
- Beta-oxidation uses NAD+ and FAD as oxidizing agents in oxidation steps
- Location:
- Biosynthesis occurs in the cytosol
- Beta-oxidation takes place in the mitochondrial matrix
- Regulation:
- Biosynthesis is stimulated by high and low levels, promoting energy storage
- Beta-oxidation is stimulated by low insulin and high glucagon levels, promoting energy release
Modifications and regulation of fatty acid synthesis
- , the process of fatty acid and triglyceride synthesis, is tightly regulated by hormones and nutritional status
- introduce double bonds into fatty acids, creating unsaturated fatty acids
- extend fatty acid chains beyond the initial 16-carbon product of FAS, producing longer-chain fatty acids
Key Terms to Review (23)
$\beta$-hydroxyacyl ACP dehydratase: $\beta$-hydroxyacyl ACP dehydratase is an enzyme that plays a crucial role in the biosynthesis of fatty acids. It catalyzes the dehydration step, removing water from the $\beta$-hydroxyacyl intermediate to form the $\alpha,\beta$-unsaturated acyl-ACP species, a key intermediate in the fatty acid elongation cycle.
$\beta$-ketoacyl ACP reductase: $\beta$-ketoacyl ACP reductase is an enzyme that plays a crucial role in the biosynthesis of fatty acids. It is responsible for the reduction of $\beta$-ketoacyl acyl carrier protein (ACP) intermediates during the fatty acid elongation cycle, which is a key step in the overall process of fatty acid synthesis.
$\beta$-ketoacyl ACP synthase: $\beta$-ketoacyl ACP synthase is a critical enzyme involved in the biosynthesis of fatty acids. It catalyzes the addition of a two-carbon unit to the growing fatty acid chain, a key step in the iterative process of fatty acid elongation.
Acetyl CoA: Acetyl Coenzyme A (acetyl CoA) is a crucial metabolic intermediate that serves as the central hub for several important biochemical pathways, including the citric acid cycle, fatty acid synthesis, and the conversion of pyruvate to acetyl CoA. It is the primary entry point for the oxidation of carbohydrates, fats, and some amino acids to generate energy in the form of ATP.
Acetyl CoA Carboxylase: Acetyl CoA carboxylase is a critical enzyme that catalyzes the rate-limiting step in the biosynthesis of fatty acids. It is responsible for the conversion of acetyl-CoA into malonyl-CoA, which serves as the two-carbon building block for the elongation of fatty acid chains.
Acyl Carrier Protein: Acyl carrier protein (ACP) is a small, acidic protein that plays a crucial role in the biosynthesis of fatty acids. It serves as a cofactor and carrier for the growing fatty acid chain during the multi-step process of fatty acid synthesis.
Beta-Oxidation: Beta-oxidation is the metabolic pathway by which fatty acids are broken down to generate acetyl-CoA, which can then enter the citric acid cycle to produce ATP. It is a crucial process in the catabolism of triacylglycerols and the biosynthesis of fatty acids.
Biotin: Biotin, also known as vitamin B7 or vitamin H, is an essential nutrient that plays a crucial role in the biosynthesis of fatty acids and carbohydrates. It is a cofactor for several key enzymes involved in these metabolic processes, making it an important consideration in the context of 29.4 Biosynthesis of Fatty Acids and 29.8 Carbohydrate Biosynthesis: Gluconeogenesis.
Citrate Shuttle: The citrate shuttle is a metabolic pathway that transports citrate, an important intermediate in the tricarboxylic acid (TCA) cycle, from the mitochondria to the cytosol. This shuttle plays a crucial role in the biosynthesis of fatty acids by providing the necessary precursor, acetyl-CoA, for fatty acid synthesis.
Coenzyme A: Coenzyme A (CoA) is a critical cofactor involved in numerous metabolic pathways, including the breakdown and synthesis of carbohydrates, fats, and amino acids. It plays a central role in connecting various biological reactions and serves as an essential component in the Citric Acid Cycle, the biosynthesis of fatty acids, and the activation of carboxylic acids.
Cytosol: The cytosol is the liquid-like substance that fills the interior of a cell, excluding the organelles and other membrane-bound structures. It is the site of many essential metabolic processes, including the biosynthesis of fatty acids.
Desaturases: Desaturases are enzymes that catalyze the introduction of double bonds into fatty acid chains, creating unsaturated fatty acids. These enzymes play a crucial role in the biosynthesis of fatty acids, a key process in 29.4 Biosynthesis of Fatty Acids.
Elongases: Elongases are a group of enzymes involved in the biosynthesis of fatty acids, responsible for the elongation of fatty acid chains by adding two-carbon units. These enzymes play a crucial role in the regulation and production of various fatty acids essential for cellular functions and physiological processes.
Enoyl ACP Reductase: Enoyl ACP reductase is an enzyme that catalyzes a critical step in the biosynthesis of fatty acids. It is responsible for the reduction of the enoyl intermediate formed during the elongation of the fatty acid chain, a key reaction in the overall pathway of fatty acid synthesis.
Fatty Acid Biosynthesis: Fatty acid biosynthesis is the metabolic process by which fatty acids are produced from acetyl-CoA and NADPH. It is a crucial pathway that generates the building blocks for various lipids, which are essential components of cell membranes, energy storage, and signaling molecules.
Fatty Acid Synthase: Fatty acid synthase is a large, multifunctional enzyme complex responsible for the de novo biosynthesis of fatty acids from acetyl-CoA and malonyl-CoA precursors. It catalyzes the step-by-step addition of two-carbon units to build up long-chain fatty acids, which are essential components of cell membranes and serve as energy storage molecules.
Glucagon: Glucagon is a hormone produced by the pancreas that plays a crucial role in regulating blood glucose levels. It is the counterpart to insulin, working to increase blood sugar when levels drop too low.
Insulin: Insulin is a hormone produced by the pancreas that regulates blood sugar levels by facilitating the uptake and utilization of glucose by cells. It is a critical component in the metabolic processes of protein structure, DNA sequencing, fatty acid biosynthesis, and carbohydrate metabolism through gluconeogenesis.
Lipogenesis: Lipogenesis is the metabolic process by which fatty acids are synthesized from non-lipid precursors, such as carbohydrates and proteins. It is a crucial anabolic pathway that allows the body to convert excess energy into storable fat for future use.
Malonyl CoA: Malonyl CoA is a key intermediate in the biosynthesis of fatty acids. It is the activated form of malonic acid, which serves as the two-carbon building block for the elongation of fatty acid chains.
NADPH: NADPH, or Nicotinamide Adenine Dinucleotide Phosphate, is a coenzyme that plays a crucial role in various metabolic processes, including the oxidation of alcohols, the biosynthesis of steroids, and the biosynthesis of fatty acids. It serves as a reducing agent, providing the necessary electrons for these important chemical reactions within the cell.
Palmitic Acid: Palmitic acid is a saturated fatty acid that is commonly found in various lipids, including waxes, fats, and oils. It plays important roles in the formation of soap, the structure of phospholipids, and the metabolic processes of fatty acid catabolism and biosynthesis.
Thioesterase: Thioesterase is an enzyme that catalyzes the hydrolysis of thioester bonds, which are found in various biological carboxylic acid derivatives such as thioesters and acyl phosphates. This enzyme plays a crucial role in the biosynthesis of fatty acids by regulating the length of the growing carbon chain.