The function of the fatty acid synthesis complex is to catalyze the synthesis of long-chain fatty acids from acetyl-CoA, malonyl-CoA, and NADPH.
Detailed Explanation of Fatty Acid Synthesis
Fatty acid synthesis is a crucial metabolic process primarily occurring in the liver, adipose tissue, and lactating mammary glands. It is the process of creating fatty acids from acetyl-CoA and NADPH. The fatty acid synthesis complex, primarily Fatty Acid Synthase (FAS), is responsible for the sequential addition of two-carbon units to a growing fatty acid chain.
Key Components and Steps
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Acetyl-CoA Transport: Acetyl-CoA, derived from carbohydrate and protein metabolism, is transported from the mitochondria to the cytoplasm (where fatty acid synthesis occurs) via the citrate shuttle.
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Formation of Malonyl-CoA: Acetyl-CoA carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA, using bicarbonate and ATP. This is the rate-limiting step in fatty acid synthesis.
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Fatty Acid Synthase (FAS) Complex: This multi-enzyme complex is the heart of fatty acid synthesis. In mammals, it is a dimer with multiple catalytic domains. FAS catalyzes the following steps:
- Loading: Acetyl-CoA and malonyl-CoA are loaded onto the Acyl Carrier Protein (ACP) domain of FAS.
- Condensation: The acetyl and malonyl groups condense, releasing CO2 and forming a β-ketoacyl-ACP.
- Reduction: The β-keto group is reduced to a β-hydroxy group using NADPH.
- Dehydration: Water is removed, forming a double bond (enoyl-ACP).
- Reduction: The double bond is reduced using NADPH, forming a saturated acyl-ACP.
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Chain Elongation: The cycle repeats, adding two-carbon units from malonyl-CoA to the growing fatty acid chain. This process continues until palmitate (a 16-carbon fatty acid) is formed.
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Termination: Palmitate is released from FAS.
Requirements for Fatty Acid Synthesis
- Acetyl-CoA: The primary building block.
- Malonyl-CoA: Provides the two-carbon units for chain elongation.
- NADPH: Acts as a reducing agent, providing the necessary electrons for reduction steps. Fatty acid synthesis consumes two molecules of NADPH + H+ for each 2-carbon unit incorporated into the fatty acid.
- ATP: Required for the carboxylation of acetyl-CoA to malonyl-CoA.
Significance
Fatty acid synthesis is vital for:
- Energy Storage: Fatty acids are stored as triglycerides in adipose tissue, providing a major energy reserve.
- Membrane Synthesis: Fatty acids are essential components of cell membranes.
- Synthesis of other lipids: Fatty acids serve as precursors for other lipids, such as phospholipids and cholesterol esters.
Regulation
Fatty acid synthesis is tightly regulated at several levels, primarily by:
- Acetyl-CoA Carboxylase (ACC): Regulation occurs through phosphorylation/dephosphorylation and allosteric modulation (citrate activation, palmitoyl-CoA inhibition).
- Insulin: Stimulates fatty acid synthesis.
- Glucagon and Epinephrine: Inhibit fatty acid synthesis.
- Dietary Factors: High carbohydrate diets promote fatty acid synthesis.
