Biochemistry II: Lipids Metabolism - Lecture 8

Fate of Absorbed Lipids

• After a fatty meal, plasma appears milky due to excess chylomicrons in venous blood, which stimulates mast cells to produce heparin.
• Heparin stimulates the lining epithelium of blood vessels to produce lipoprotein lipase (plasma clearing factor).
• Lipoprotein lipase acts on triacylglycerols of chylomicrons, converting them into glycerol and free fatty acids.

Fate of Glycerol and Fatty Acids

• Glycerol and fatty acids are taken up by different tissues for various functions:
• Formation of depot fat (mainly triacylglycerols in adipose tissue)
• Oxidation for energy production (fatty acids converted to acetyl CoA and glycerol to dihydroxyacetone phosphate)
• Glucose formation by gluconeogenesis (glycerol → glucose, odd-numbered fatty acid oxidation → propionyl CoA → glucose)
• Synthesis of biologically active compounds (e.g., steroids)
• Synthesis of tissue fats (structural fats, e.g., phospholipids and cholesteryl ester)

Body Lipids

• Two types of lipids: tissue lipids (constant element) and adipose tissue (depot fat, variable element)
• Tissue lipids: enter the structure of body cells (e.g., cell membrane, mitochondria), mainly cholesterol, phospholipids, and some triacylglycerols; never oxidized to give energy
• Adipose tissue:
• White adipose tissue (energy): present under skin, composed of triacylglycerols; provides energy during fasting
• Brown adipose tissue (heat): certain areas of adipose tissue, contains high amounts of mitochondria

Lipogenesis and Lipolysis

• Lipogenesis: synthesis of triacylglycerol from fatty acids and glycerol
  1. Activation of fatty acids
  2. Synthesis of glycerol-3-phosphate
  3. Esterification
• Lipolysis: hydrolysis of triacylglycerols in adipose tissue into glycerol and fatty acids
• Steps: hormone-sensitive lipase enzymes, diacylglycerol lipase, and monoacylglycerol lipase

Regulation of Lipogenesis and Lipolysis

• In the fed state: increased lipogenesis, insulin/glucagon ratio stimulates lipoprotein lipase, increasing fatty acid uptake in adipose cells
• In the fasting state: increased lipolysis, insulin/glucagon ratio decrease, and hormone-sensitive lipase enzyme is activated

De Novo Fatty Acid Synthesis

• Occurs in cytoplasm of liver, adipose tissue, mammary gland, lung, and kidney
• Requirements: acetyl CoA, NADPH+H, and fatty acid synthase complex
• Steps: A. Carboxylation of acetyl CoA to malonyl CoA B. Transport of acetyl-CoA to the site 1 of ACP C. Transport of malonyl-CoA to the site 2 ACP D. Synthesis of palmitate
• Fates of palmitate: esterification, chain elongation, and desaturation

Regulation of De Novo Fatty Acid Synthesis

• Allosteric regulation: citrate stimulates acetyl-CoA carboxylase, while long-chain fatty acids and palmitate inhibit it
• Covalent modification: insulin increases the dephosphorylated form, stimulating FA synthesis, while glucagon and epinephrine increase the phosphorylated form, inhibiting FA synthesis

Fate of Absorbed Lipids

• After a fatty meal, plasma appears milky due to excess chylomicrons in venous blood, which stimulates mast cells to produce heparin.
• Heparin stimulates the lining epithelium of blood vessels to produce lipoprotein lipase (plasma clearing factor).
• Lipoprotein lipase acts on triacylglycerols of chylomicrons, converting them into glycerol and free fatty acids.

Fate of Glycerol and Fatty Acids

• Glycerol and fatty acids are taken up by different tissues for various functions:
• Formation of depot fat (mainly triacylglycerols in adipose tissue)
• Oxidation for energy production (fatty acids converted to acetyl CoA and glycerol to dihydroxyacetone phosphate)
• Glucose formation by gluconeogenesis (glycerol → glucose, odd-numbered fatty acid oxidation → propionyl CoA → glucose)
• Synthesis of biologically active compounds (e.g., steroids)
• Synthesis of tissue fats (structural fats, e.g., phospholipids and cholesteryl ester)

Body Lipids

• Two types of lipids: tissue lipids (constant element) and adipose tissue (depot fat, variable element)
• Tissue lipids: enter the structure of body cells (e.g., cell membrane, mitochondria), mainly cholesterol, phospholipids, and some triacylglycerols; never oxidized to give energy
• Adipose tissue:
• White adipose tissue (energy): present under skin, composed of triacylglycerols; provides energy during fasting
• Brown adipose tissue (heat): certain areas of adipose tissue, contains high amounts of mitochondria

Lipogenesis and Lipolysis

• Lipogenesis: synthesis of triacylglycerol from fatty acids and glycerol
  1. Activation of fatty acids
  2. Synthesis of glycerol-3-phosphate
  3. Esterification
• Lipolysis: hydrolysis of triacylglycerols in adipose tissue into glycerol and fatty acids
• Steps: hormone-sensitive lipase enzymes, diacylglycerol lipase, and monoacylglycerol lipase

Regulation of Lipogenesis and Lipolysis

• In the fed state: increased lipogenesis, insulin/glucagon ratio stimulates lipoprotein lipase, increasing fatty acid uptake in adipose cells
• In the fasting state: increased lipolysis, insulin/glucagon ratio decrease, and hormone-sensitive lipase enzyme is activated

De Novo Fatty Acid Synthesis

• Occurs in cytoplasm of liver, adipose tissue, mammary gland, lung, and kidney
• Requirements: acetyl CoA, NADPH+H, and fatty acid synthase complex
• Steps: A. Carboxylation of acetyl CoA to malonyl CoA B. Transport of acetyl-CoA to the site 1 of ACP C. Transport of malonyl-CoA to the site 2 ACP D. Synthesis of palmitate
• Fates of palmitate: esterification, chain elongation, and desaturation

Regulation of De Novo Fatty Acid Synthesis

• Allosteric regulation: citrate stimulates acetyl-CoA carboxylase, while long-chain fatty acids and palmitate inhibit it
• Covalent modification: insulin increases the dephosphorylated form, stimulating FA synthesis, while glucagon and epinephrine increase the phosphorylated form, inhibiting FA synthesis