1. Synthesis of triacyglycerol (TAG) in the liver 1- Activation of fatty acids into acyl CoA: In the presence of ATP and CoA, the enzyme thiokinase (or called Acyl CoA synthetase) catalyses the activation of fatty acids into acyl CoA. RCOOH+2ATP + CoASH → RCO ~ SCoA acyl CoA

2. 2- Activation of glycerol: The active form of glycerol is glycerol-3-phosphate Sources of glycerol-3-phosphate in the liver a.From glycerol: The liver can use glycerol to produce glycerol 3-phosphate by a reaction that requires ATP and is catalyzed by glycerol kinase. b. From glucose by glycolysis: liver can convert glucose, through glycolysis, to dihydroxyacetone phosphate (DHAP), which is reduced by NADH to glycerol 3- phosphate.

3. 3-Combination of acyl CoA with glycerol-3-phosphate: a. In the liver, glycerol 3-phosphate reacts with two acyl CoAs to form phosphatidic acid. Acyl group is transferred into glycerol 3-phosphate by acyltransferase enzyme b. The phosphate group is removed from phosphatidic acid to form 1, 2 diacylglycerol (1, 2 DAG), which reacts with another acyl CoA to form a triacylglycerol (TAG). c. TAG synthesized in the liver will be packed into lipoprotein called VLDL which enter blood. In blood, TAG carried on VLDL will be hydrolysed by lipoprotein lipase (LPL) into fatty acids which enter adipose tissue and stored as TAG as illustrated in next slides. NB: Lipoprotein lipase (LPL) is attached to membranes of cells in the walls of capillaries in adipose tissue. LPL is synthesized in adipose cells and is secreted by a process stimulated by insulin, which is elevated after a meal.

5. Acyl CoA, acyl transferase TAG Synthesis of TAG in liver C

6. 1- Sources of fatty acids in adipose tissues: - Adipose tissue synthesized fatty acids from excess CHO (the precursor is acetyl CoA). As discussed before. -Fatty acids released from chylomicrons (that carry dietary TAG) and VLDL (that carry TAG synthesized in liver) by lipoprotein lipase are taken up by adipose cells. -- These fatty acids are activated to Acyl CoA

7. 2- Sources of Glycerol-3-Phosphate in adipose tissue: Glycerol is NOT used as source of glycerol-3-phosphate because adipose tissue lack (doesn’t contain) glycerolkinase. Glycerol-3-phosphate is produced in adipose tissue only from glucose by glycolysis. The transport of glucose into adipose cells is stimulated by insulin, which is elevated after a meal. Glucose is converted to DHAP, which is reduced by NADH to form glycerol 3- phosphate. 3- Glycerol-3-phosphate combine with acyl CoA to produce TAG: These TAG are stored in adipose tissue and considered as energy reservoir that can be used as major source of energy in case of starvation or in fasting state.

9. Sources of glycerol-3-phosphate in liver and adipose tissue