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The wonderful journey of fatty acid synthesis: how does it start from acetate-CoA?
In biochemistry, fatty acid synthesis is the process by which fatty acids are created from acetate-coenzyme A (acetyl-CoA) and NADPH by the action of fatty acid synthase. This process takes place in the cytoplasm of the cell. Most of the acetate-CoA converted into fatty acids in the human body comes mainly from carbohydrates as a product of glycolysis. In addition, glycolysis also provides glycerol, which combines with three fatty acids through ester bonds to eventually form triglycerides, commonly known as "fat." The final product of fat involves the entire process of lipid synthesis.
The main components of cell membranes are phospholipids, which surround organelles such as the nucleus, mitochondria, endoplasmic reticulum, and Golgi bodies.
In addition to fatty acid synthesis in the cytoplasm, there is mitochondrial fatty acid synthesis (mtFASII), in which malonyl-CoA is generated from malonate by malonyl-CoA synthetase (ACSF3) and then A series of intermediate steps ultimately produce octanoyl-CoA (C8).
Straight chain fatty acids
There are two types of straight-chain fatty acids: saturated and unsaturated. The latter is generated by the former.
Saturated straight chain fatty acids
Saturated straight-chain fatty acids are synthesized through six repeated reaction steps until 16-carbon palmitic acid is produced. These reactions are performed by fatty acid synthase II (FASII), which is usually a complex containing multiple enzymes. FASII is mainly found in prokaryotes, plants, fungi and parasites, and is also present in mitochondria. In animals and some fungi, these reactions are carried out by fatty acid synthase I (FASI), a large dimer that contains all the enzyme activities required for fatty acid synthesis.
NADPH is a reducing agent in fatty acid synthesis, while NAD is an oxidizing agent during β-oxidation.
During the synthesis process, the source of the reducing agent NADPH mainly comes from two aspects. One is generated through the oxidative decarboxylation reaction of "NADP+-dependent malic enzyme", and the other comes from the five-carbon phosphate that converts glucose into ribose. way. In these processes, pyruvate is an important intermediary in the conversion of carbohydrates to fatty acids.
Carbohydrates are converted into fatty acids
In humans, fatty acids are primarily formed in the liver and adipose tissue, and also in the mammary glands during lactation. The pyruvate produced by glycolysis needs to be converted into acetate-CoA and then transported into the cytoplasm for the synthesis of fatty acids and cholesterol. It is worth noting that this fluid cannot directly enter the cytoplasm.
Animals cannot synthesize carbohydrates from fatty acids
In animals, the main stored fuel is fat. A young adult's fat storage is generally between 15 and 20 kg, but it varies greatly depending on age, gender and personal characteristics.
The fatty acid metabolism pathway and sugar production pathway of animals are mutually inhibited, making it impossible to convert fatty acids into carbohydrates.
Fatty acids are broken down into acetate-CoA by β-oxidation in the mitochondria, while synthesis occurs in the cytoplasm. These two processes not only occur in different areas, but also use different substrates and chemical reactions. . This mutually inhibitory relationship ensures the balance between fatty acid synthesis and decomposition.
Regulatory mechanism
The conversion of acetate-CoA to malonyl-CoA is regulated by acetate-CoA carboxylase, which is a regulatory point for the synthesis of saturated straight-chain fatty acids and is affected by phosphorylation and allosteric regulation.
Unsaturated straight chain fatty acids
The synthesis of unsaturated fatty acids can be processed through either anaerobic or aerobic pathways. Many bacteria synthesize unsaturated fatty acids using anaerobic pathways that do not require oxygen but rely on specific enzymes to insert double bonds during the synthesis process.
In eukaryotic cells, the major aerobic unsaturated fatty acid synthesis pathway relies on desaturases to convert saturated fatty acids into unsaturated fatty acids.
Unsaturated fatty acids are an important component of biodiversity, and some essential fatty acids must be obtained through the diet because mammals cannot synthesize them. These essential fatty acids play important roles in the activities within cells, including serving as precursors of bioactive compounds and participating in the regulation of various cellular functions and signaling.
The process of fatty acid synthesis is like a precise journey, starting from acetate-CoA, going through multiple regulation, and finally converting into diverse fatty acid types. Which processes are particularly critical to human physiology?
