DAG Transacylase Pathway for Triglyceride Synthesis
Introduction
Triglyceride (triacylglycerol) synthesis is a crucial biochemical process that stores energy in adipose tissues. The diacylglycerol acyltransferase (DGAT) enzyme plays a central role in the final step of triglyceride synthesis through the DAG transacylase pathway.
Overview of Triglyceride Synthesis
- Triglycerides are composed of one glycerol molecule and three fatty acid chains.
- The synthesis starts with glycerol-3-phosphate (from glycolysis) and proceeds through the following intermediates: lysophosphatidic acid → phosphatidic acid → diacylglycerol (DAG) → triacylglycerol (TAG).
DAG Transacylase Pathway (DGAT Pathway)
The DAG transacylase pathway involves the following reaction:
DAG + Acyl-CoA → TAG + CoA
- This reaction is catalyzed by the enzyme DGAT (diacylglycerol acyltransferase).
- DGAT transfers a fatty acid from acyl-CoA to the hydroxyl group on DAG, forming the third ester bond and completing the triglyceride molecule.
Types of DGAT Enzymes
- DGAT1: Found in various tissues including intestines and adipose tissues. Involved in dietary fat absorption and energy storage.
- DGAT2: More abundant in the liver and adipose tissue, mainly responsible for de novo synthesis of triglycerides.
Physiological Role
- Enables long-term energy storage in adipocytes.
- Supports lipid droplet formation in liver cells and other tissues.
- Maintains lipid homeostasis and prevents accumulation of toxic intermediates like DAGs and fatty acyl-CoAs.
Medical Relevance
- Overactivity of DGAT is associated with obesity and fatty liver disease.
- Inhibitors of DGAT are being studied for therapeutic use in treating metabolic disorders.
Conclusion
The DAG transacylase pathway, via DGAT enzymes, is the final and essential step in triglyceride biosynthesis. It facilitates the storage of excess energy and plays a central role in lipid metabolism, energy balance, and metabolic health.