3.12 actual
Fatty Acid Synthesis Overview
Fatty acid synthesis occurs when there is a high energy state, where excess energy results in fatty acid production rather than breakdown.
Key reactants involved: Energy (ATP), Acetyl CoA, NADPH, Malonyl CoA.
Transport of Acetyl CoA
Acetyl CoA is transported from mitochondria to cytosol through citrate, after being converted from oxaloacetate.
Mitochondrial actions lead to increased citrate concentration that leaves the mitochondria to participate in synthesis reactions.
Key Enzyme in Fatty Acid Synthesis
Fatty Acid Synthase (FAS) is a large complex that synthesizes fatty acids.
In mammals, it comprises a single polypeptide, whereas, in organisms like E. coli, it comprises multiple polypeptides.
The acyl carrier protein (ACP) and beta-keto-acyl ACP synthase (KS) are important thiol groups used to carry and attach intermediates in the synthesis pathway.
Mechanisms of Synthesis
Initial process involves Acetyl CoA bound to KS and Malonyl CoA bound to ACP.
The acetyl unit condenses with malonyl to form a four-carbon chain (after loss of CO2).
Reduction reactions occur utilizing NADPH to saturate double bonds formed during dehydration.
Each cycle adds 2-carbon units to the growing fatty acid chain, allowing for elongation.
Cycles for Production
Making a 16-carbon fatty acid (palmitate) requires 7 cycles of fatty acid synthesis, each adding 2 carbons.
For every new palmitate molecule, 8 Acetyl CoA, 7 Malonyl CoA, and 14 NADPH are needed, with results differing during synthesis redemption forms and CO2 release.
Regulation of Fatty Acid Synthesis
The limiting step in fatty acid synthesis is the conversion of Acetyl CoA to Malonyl CoA via acetyl-CoA carboxylase, which needs biotin and CO2.
Hormonal signaling plays a critical role: Insulin promotes storage of fat (synthesis), while glucagon and epinephrine promote fat breakdown.
Malonyl CoA acts as an inhibitor for fatty acid oxidation, ensuring that synthesis and breakdown do not occur simultaneously.
Fatty Acid Modifications
Fatty acids longer than 16 carbons or with multiple double bonds are synthesized in the smooth ER and require dietary essential fatty acids as mammals cannot create them.
Fatty acid synthesis/saturation processes require NADPH and must follow strict biochemical principles.
Conclusion
Emphasized the importance of diet for essential fatty acids.
Next topic will cover the synthesis of triglycerides, combining previously learned concepts of glycerol and fatty acids.
Fatty Acid Synthesis Overview
Fatty acid synthesis occurs primarily during a high energy state, characterized by an abundance of energy substrates. Under such conditions, excess energy is directed towards the production of fatty acids rather than their breakdown, which is crucial for energy storage.
Key reactants involved in this anabolic process include Energy in the form of ATP, Acetyl CoA which serves as the carbon skeleton for fatty acids, NADPH which provides reducing power, and Malonyl CoA which acts as a building block for extending the fatty acid chain.
Transport of Acetyl CoA
Acetyl CoA, which is generated in the mitochondria, is transported to the cytosol where fatty acid synthesis occurs. This transport is facilitated through its conversion to citrate. Citrate is formed by the condensation of Acetyl CoA and oxaloacetate, and it is shuttled out of the mitochondria as its concentration rises following an energy-rich state.
Key Enzyme in Fatty Acid Synthesis
The key enzyme in fatty acid synthesis is Fatty Acid Synthase (FAS), a large multi-functional enzyme complex that orchestrates the synthesis of fatty acids. In mammals, FAS is organized as a single polypeptide chain that contains several functional domains, whereas, in certain bacteria such as E. coli, FAS is composed of multiple polypeptides that operate as a modular system.
Of particular significance are the acyl carrier protein (ACP) and beta-keto-acyl ACP synthase (KS), which contain important thiol groups necessary for carrying and attaching the acyl intermediates throughout the synthesis pathway.
Mechanisms of Synthesis
The initial steps of fatty acid synthesis involve the binding of Acetyl CoA to KS and Malonyl CoA to ACP. The acetyl unit undergoes condensation with malonyl to form a four-carbon chain, with the decarboxylation of Malonyl CoA releasing CO2.
Reduction reactions are essential in the synthesis process, utilizing NADPH to saturate and reduce double bonds formed during dehydration reactions, thus increasing the stability of the fatty acid chains. Each elongation cycle adds 2-carbon units to the growing fatty acid chain until the desired length is achieved.
Cycles for Production
The synthesis of a 16-carbon fatty acid, namely palmitate, necessitates a total of 7 cycles of fatty acid synthesis, with each cycle contributing 2-carbon units. To produce one palmitate molecule, the metabolic investment includes 8 Acetyl CoA, 7 Malonyl CoA, and 14 NADPH, highlighting the resource requirements for fatty acid biosynthesis, and results include release and recycling of carbon dioxide.
Regulation of Fatty Acid Synthesis
The regulation of fatty acid synthesis is tightly controlled, with the limiting step being the carboxylation of Acetyl CoA to Malonyl CoA, facilitated by the enzyme acetyl-CoA carboxylase, which requires biotin as a cofactor and carbon dioxide.
Hormonal signals play a crucial role in regulating this metabolic pathway; Insulin promotes the storage of fats and encourages synthesis, while glucagon and epinephrine stimulate breakdown pathways, ensuring that energy homeostasis is maintained.
Malonyl CoA also serves as an inhibitor for fatty acid oxidation, thus ensuring that fatty acid synthesis and breakdown do not occur simultaneously, which is critical for metabolic efficiency and energy balance.
Fatty Acid Modifications
Fatty acids that are longer than 16 carbons or contain multiple double bonds are synthesized in the smooth endoplasmic reticulum (SER), and their production relies on dietary essential fatty acids, since mammals lack the ability to synthesize these vital nutrients.
The processes of fatty acid synthesis and desaturation require NADPH and follow well-established biochemical principles to ensure proper functionality in metabolic pathways.
Conclusion
The notes emphasize the crucial importance of dietary intake for obtaining essential fatty acids that the body cannot synthesize.
The subsequent topic of discussion will cover the synthesis of triglycerides, integrating the previously learned concepts of glycerol and fatty acids, to expand understanding of lipid biology and metabolism.