Fatty acid ligase, specifically long-chain fatty-acid-CoA ligase (also known as acyl-CoA synthetase), functions to catalyze the synthesis of fatty acyl-CoAs from free fatty acids, coenzyme A (CoA), and ATP. This process is crucial for several metabolic pathways.
Key Functions of Fatty Acid Ligase:
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Activation of Fatty Acids: The primary function is to activate fatty acids by converting them into fatty acyl-CoA. This activation is a necessary step for fatty acid beta-oxidation, glycerolipid synthesis, and protein acylation.
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Beta-Oxidation: Fatty acyl-CoA is transported into the mitochondria, where it undergoes beta-oxidation, a process that breaks down fatty acids to generate energy in the form of ATP.
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Glycerolipid Synthesis: Fatty acyl-CoA is used in the synthesis of various glycerolipids, such as triglycerides and phospholipids, which are important components of cell membranes and energy storage molecules.
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Regulation of Fatty Acid Metabolism: Long-chain fatty-acid-CoA ligase may also play a role in regulating fatty acid synthesis, potentially contributing to the suppression of fatty acid synthesis.
Detailed Explanation:
The reaction catalyzed by fatty acid ligase can be summarized as follows:
Fatty Acid + CoA + ATP --> Fatty Acyl-CoA + AMP + PPi (pyrophosphate)
This reaction occurs in two steps:
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Formation of Acyl-AMP: The fatty acid reacts with ATP to form an acyl-AMP intermediate, releasing pyrophosphate (PPi).
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Transfer to CoA: The acyl group is then transferred from acyl-AMP to coenzyme A (CoA), forming fatty acyl-CoA and releasing AMP.
The pyrophosphate (PPi) produced in the first step is subsequently hydrolyzed by pyrophosphatase, making the overall reaction irreversible and driving the formation of fatty acyl-CoA.
Examples of Fatty Acid Ligases:
Different isoforms of fatty acid ligase exist, each with specificity for fatty acids of different chain lengths. Examples include:
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Long-chain fatty-acid-CoA ligase (ACS): Primarily activates long-chain fatty acids (12-20 carbons).
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Very long-chain fatty-acid-CoA ligase (VLCACS): Activates very long-chain fatty acids (22 carbons or more).
The specific isoform present in a cell or tissue depends on the cell's metabolic needs and the types of fatty acids it processes.
In summary, fatty acid ligase is essential for activating fatty acids, enabling their utilization in various metabolic pathways like beta-oxidation and glycerolipid synthesis, and potentially playing a regulatory role in fatty acid metabolism.
