NUTR 470 1st Edition Lecture 14-Nutritional Regulation of Lipogenesis-Liver• The liver is the predominant place for the synthesis of triglycerides, which are then used for VLDL formation.-Adipose tissue• Adipose tissue is the predominant place for the storage of triglycerides.-Synthesis and Storage of Triglycerides-Synthesis of Triglycerides— from free fatty acids and glycerol-Source of Free Fatty Acids• Free fatty acids are generated from CMs and VLDLs, as well as de novo lipogenesis.-Hydrolysis of chylomicrons and VLDLs -FFAs are removed from lipoproteins by LPL. -Uptake of FFAs is mediated through fatty acid transporter complex. • De novo lipogenesis -Excessive glucose is converted into FFA.--Source of Glycerol • Glycerol-3-phosphate, the active form of glycerol, is required for the synthesis of triglycerides. • Glycerol-3-phosphate- Dihydroxyacetone phosphate, generated through glycolysis, is converted to Gly-3-P by GPDH. • what to know: that glycerol-3-phosphate is the active form of glycerol• backbone from glycolysis• When you have extra citrate you send it out of cytosol and can begin lipogenesis— start to form backbone for glycolysis• from pyruvate oxidation … start lipogenesis • there are activators and inhibitors of TCA cycle that relate to lipid formationThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.-Direct phosphorylation of glycerol also generates Gly-3-P. -Lipogenesis • De novo synthesis of fatty acids occurs in the cytosol. -Place • Lipogenesis occurs in many tissues, but predominantly in the liver. -Substrate • Acetyl-CoA • NADPH — will not discuss too much.-De novo synthesis of fatty acids occurs in the cytosol.• Substrates of lipogenesis -Acetyl-CoA – brought into cytosol through citrate-pyruvate cycle. -NADPH – generated after conversion of malate to pyruvate by malic enzyme -NADPH – generated from pentose phosphate shunt Mechanism of citrate in excess leaving the cell to make substrates of lipogenesis- One rate determining enzyme: Acetyl-CoA carboxylase (ACC)-Key Reactions of Lipogenesis• Acetyl-CoA —- > Malonyl-CoA-ACC is the most important enzyme in the regulation of lipogenesis. • catalyzes the rate determining step-Acetyl-CoA carboxylase (ACC) catalyzes the generation of malonyl-CoA as the first step of lipogenesis. -Malonyl-CoA is the most important regulator of fatty acid oxidation -Malonyl-CoA, at high levels, inhibits fatty acid oxidation by suppressing the transfer of long chain fatty acids into mitochondria. • think about feeding— glucose is the most powerful activator of lipogenesis b/c it increases pyruvate oxidation-plenty substrate and plenty enzyme• malonyl-Coa—> —> Palmitate-FAS is a 544-kd homodimer. -Fatty acid synthase (FAS) catalyzes seven steps in the fatty acid synthesis pathway, resulting in the synthesis of palmitate from malonyl-coA and acetyl-coA. -Regulation of Lipogenesis • Lipogenesis is regulated by nutritional and hormonal signals. • Glucose -Glucose, through glycolysis and oxidation of pyruvate, provides substrates for lipogenesis -Glucose, through glucose signaling, stimulates ACC and FAS gene expression. • Insulin -Insulin stimulates glycolysis, which in turn provides substrates for lipogenesis. -Insulin, through insulin signaling, stimulates ACC and FAS gene expression. -Glucagon• Glucagon activates AMP-activated protein kinase through cAMP-dependent protein kinase, which in turn phosphorylates and inactivates ACC. • Increase of Glucagon — increases Lipogenesis-Synthesis of Triglycerides • Free fatty acids are stored for future use as triglycerides in all cells, but primarily in adipocytes of adipose tissue.-Diglyceride acyltransferase (DGAT) catalyzes the formation of triglycerides from diacylglycerol and acyl-CoA. -DGAT is a potential therapeutic target for obesity and diabetes.-Summary -Lipogenesis -Regulation of lipogenesis -Source of acetyl-CoA and NADPH Synthesis of