Overview
This lecture explains the process of triglyceride (triacylglycerol) synthesis, detailing the sources of its components, the stepwise enzymatic reactions, and final storage and transport within the body.
Constituents and Overview of Triglyceride Synthesis
- Triglyceride synthesis (lipogenesis) requires three fatty acyl-CoA molecules and one glycerol backbone.
- Fatty acyl-CoA is derived from fatty acid synthesis, using malonyl-CoA and fatty acid synthase.
Glycerol-3-Phosphate Formation
- Glycerol backbone can originate from two sources: glycolysis (via dihydroxyacetone phosphate, DHAP) or lipolysis in adipose tissue.
- DHAP is converted into glycerol-3-phosphate using NADH.
- In the liver, glycerol kinase catalyzes the phosphorylation of glycerol to form glycerol-3-phosphate.
Stepwise Assembly of Triglyceride
- Glycerol-3-phosphate combines sequentially with three fatty acyl-CoA molecules.
- Step 1: Fatty acyl-CoA added to the first carbon via acyl transferase, forming lysophosphatidic acid (monoacylglycerol).
- Step 2: Another fatty acyl-CoA (must be unsaturated) added to the second carbon, forming phosphatidic acid (diacylglycerol).
- Step 3: Phosphatase enzyme (phosphatidic phosphatase) removes the phosphate from carbon three, then acyl transferase adds the third fatty acyl-CoA, forming triglyceride (triacylglycerol).
Alternative Nomenclature and Molecular Types
- Monoacylglycerol (MAG): one fatty acid attached.
- Diacylglycerol (DAG): two fatty acids attached.
- Triacylglycerol (TAG or triglyceride): three fatty acids attached.
Packaging and Storage of Triglycerides
- Triglycerides are packaged into very-low-density lipoproteins (VLDL) in the liver.
- VLDLs transport triglycerides through the bloodstream to adipose tissue for storage.
- Lipoprotein lipase at adipose sites breaks down circulating triglycerides for uptake and storage as new triglycerides.
Key Terms & Definitions
- Triglyceride/Triacylglycerol (TAG) — A lipid made of three fatty acids linked to glycerol.
- Fatty Acyl-CoA — Fatty acid linked to coenzyme A, activated for metabolism.
- Glycerol-3-Phosphate — A phosphorylated glycerol used as the backbone for triglyceride synthesis.
- Acyl Transferase — Enzyme that transfers fatty acyl groups to glycerol-3-phosphate.
- Phosphatidic Acid — Intermediate with two fatty acid chains and a phosphate group.
- Phosphatase — Enzyme that removes a phosphate group.
- VLDL (Very-Low-Density Lipoprotein) — Lipoprotein particle that transports triglycerides to tissues.
- Lipoprotein Lipase — Enzyme that breaks down circulating triglycerides for storage in adipose tissue.
Action Items / Next Steps
- Review fatty acid synthesis steps as a prerequisite for triglyceride synthesis.
- Prepare for the next lecture on cholesterol metabolism, including roles of lipoproteins.