Lipid Metabolism Lesson 2

Lipid Metabolism - Lesson 2

• Fatty acid synthesis is a crucial process in lipid metabolism.
• Fatty acids are categorized based on chain length (short, medium, long, very long), bond type (saturated, unsaturated), nutritional classification (essential, nonessential), and eicosanoids.
• Most biological fatty acids have carbon chain lengths between 12 and 22.
• Fatty acids with only single bonds between carbons are called saturated fatty acids.
• Fatty acids with one or more double bonds are called unsaturated fatty acids; these are further categorized as monounsaturated (MUFA) or polyunsaturated (PUFA).
• Examples of important fatty acids include palmitoleic acid (MUFA), oleic acid (MUFA), linoleic acid (PUFA), a-linolenic acid (PUFA), y-linolenic acid (PUFA), and arachidonic acid (PUFA).

Fatty Acid Synthesis System

• There are three systems for fatty acid production: synthesis, elongation, and desaturation.
• Fatty acid synthesis takes place in the cytoplasm and involves the conversion of acetyl-CoA to palmitic acid.
• Palmitic acid is a saturated fatty acid with 16 carbons and can be further modified.
• The process requires acetyl-CoA, malonyl-CoA, NADPH, and ATP.
• Glucose is the primary substrate for lipogenesis in most mammals.
• The pathway begins with the transportation of acetyl-CoA from the mitochondria to the cytosol.
• Acetyl-CoA is converted to malonyl-CoA in a series of steps, catalyzed by acetyl-CoA carboxylase (ACC).

Cytoplasmic Synthesis System

• The formation of palmitic acid involves transferring an acetyl group to the –SH group of ACP followed by the addition of a three-carbon malonyl group. This process creates a four-carbon unit from the acetyl group and malonyl intermediate. Repeated cycles add two carbons at a time through a ketoacyl-ACP synthase, reduction by NADPH, and dehydration to produce the saturated acyl group. The process is repeated to form a 16-carbon saturated fatty acid (palmitic acid).

Fatty Acid Elongation System

• This system is responsible for elongating saturated and unsaturated fatty acids from 10 carbons onwards to form very long fatty acids like C22 or C24.
• Malonyl CoA is the acetyl donor, adding two carbons at a time, using reactions similar to those in fatty acid synthesis. This process happens in the mitochondria or SER, with the SER microsomal system being more prominent.
• The system uses NADPH as a source of reducing equivalents.

Microsomal Desaturation System

• This system creates monounsaturated fatty acids (MUFAs) by introducing double bonds into saturated fatty acids.

• The primary location is the endoplasmic reticulum.

• These systems work to create MUFAs starting with palmitoyl-CoA or stearoyl-CoA.

• The 9 position is where the double bond is introduced.

• The desaturation of fatty acids results in monounsaturated fatty acids (MUFA) like palmitoleic acid and oleic acid.

• Both fasting and low insulin levels inhibit the desaturation and elongation systems.