Metabolism of Macromolecules: Lipid Digestion and Absorption

Triacylglycerols (triglycerides) are the major form of energy, making up 90% of dietary lipids
They provide 6 times more energy per unit weight than glycogen
Triacylglycerols are water-insoluble and require emulsification by bile salts and bile acids in the small intestine for digestion
Bile acids have a detergent character, helping to solubilize and absorb lipids in the gut
Lipid absorption occurs in enterocytes as micelles with bile salts and lecithin or as lipid-protein complexes
Lipids are transported as lipoproteins, which are lipid-protein complexes that make lipids soluble

Lipid metabolism involves the breakdown of fats (lipids) for energy and storage
The process involves multiple steps and enzymes that are tightly regulated
Biosynthesis of triacylglycerols (lipogenesis) involves the incorporation of fatty acids into triacylglycerols for storage or into phospholipid components of membranes
Triacylglycerols and glycerophospholipids share two precursors: fatty acyl-CoA and L-glycerol 3-phosphate
The majority of glycerol 3-phosphate is derived from dihydroxyacetone phosphate (DHAP) by the action of cytosolic NAD-linked glycerol 3-phosphate dehydrogenase
Fatty acyl-CoAs are formed from fatty acids by acyl-CoA synthetases, the same enzymes responsible for the activation of fatty acids for β-oxidation

The first stage in biosynthesis is the acylation of the two free hydroxyl groups of L-glycerol 3-phosphate by two molecules of fatty acyl-CoA to yield diacylglycerol 3-phosphate (phosphatidic acid)
Phosphatidic acid is a central intermediate in lipid biosynthesis and can be converted to a triacylglycerol or a glycerophospholipid
In the pathway to triacylglycerols, phosphatidic acid is hydrolyzed by phosphatidic acid phosphatase (lipin) to form a 1,2-diacylglycerol
Diacylglycerols are then converted to triacylglycerols by transesterification with a third fatty acyl-CoA

Lipolysis is the process by which stored fat in adipose tissue is broken down into free fatty acids and glycerol
This process is regulated by hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL)
Fatty acids are mobilized from triacylglycerols and oxidized to meet the energy needs of the cell or organism

Fatty acid oxidation involves the breakdown of fatty acids into acetyl-CoA, which is then processed in the citric acid cycle
The process of degradation converts an aliphatic compound into a set of activated acetyl units (acetyl-CoA) that can be processed by the citric acid cycle
The repetitive four-step process by which fatty acids are converted into acetyl-CoA is called β-oxidation
Triacylglycerols are highly concentrated stores of metabolic energy because they are reduced and anhydrous

Ketogenesis occurs when excess fatty acids are converted into ketone bodies, such as acetoacetate, β-hydroxybutyrate, and acetone
This process occurs in the liver and is regulated by enzymes such as β-ketoacyl-CoA transferase and β-hydroxybutyrate dehydrogenase
Ketone bodies are produced when the supply of carbohydrates is low and the body needs to use fat as its primary fuel source
Acetoacetate and D-β-hydroxybutyrate are transported by the blood to tissues other than the liver, where they are converted to acetyl-CoA and oxidized in the citric acid cycle

Triacylglycerols (triglycerides) are the major form of energy, making up 90% of dietary lipids
They provide 6 times more energy per unit weight than glycogen
Triacylglycerols are water-insoluble and require emulsification by bile salts and bile acids in the small intestine for digestion
Bile acids have a detergent character, helping to solubilize and absorb lipids in the gut
Lipid absorption occurs in enterocytes as micelles with bile salts and lecithin or as lipid-protein complexes
Lipids are transported as lipoproteins, which are lipid-protein complexes that make lipids soluble

Lipid metabolism involves the breakdown of fats (lipids) for energy and storage
The process involves multiple steps and enzymes that are tightly regulated
Biosynthesis of triacylglycerols (lipogenesis) involves the incorporation of fatty acids into triacylglycerols for storage or into phospholipid components of membranes
Triacylglycerols and glycerophospholipids share two precursors: fatty acyl-CoA and L-glycerol 3-phosphate
The majority of glycerol 3-phosphate is derived from dihydroxyacetone phosphate (DHAP) by the action of cytosolic NAD-linked glycerol 3-phosphate dehydrogenase
Fatty acyl-CoAs are formed from fatty acids by acyl-CoA synthetases, the same enzymes responsible for the activation of fatty acids for β-oxidation

The first stage in biosynthesis is the acylation of the two free hydroxyl groups of L-glycerol 3-phosphate by two molecules of fatty acyl-CoA to yield diacylglycerol 3-phosphate (phosphatidic acid)
Phosphatidic acid is a central intermediate in lipid biosynthesis and can be converted to a triacylglycerol or a glycerophospholipid
In the pathway to triacylglycerols, phosphatidic acid is hydrolyzed by phosphatidic acid phosphatase (lipin) to form a 1,2-diacylglycerol
Diacylglycerols are then converted to triacylglycerols by transesterification with a third fatty acyl-CoA

Lipolysis is the process by which stored fat in adipose tissue is broken down into free fatty acids and glycerol
This process is regulated by hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL)
Fatty acids are mobilized from triacylglycerols and oxidized to meet the energy needs of the cell or organism

Fatty acid oxidation involves the breakdown of fatty acids into acetyl-CoA, which is then processed in the citric acid cycle
The process of degradation converts an aliphatic compound into a set of activated acetyl units (acetyl-CoA) that can be processed by the citric acid cycle
The repetitive four-step process by which fatty acids are converted into acetyl-CoA is called β-oxidation
Triacylglycerols are highly concentrated stores of metabolic energy because they are reduced and anhydrous

Ketogenesis occurs when excess fatty acids are converted into ketone bodies, such as acetoacetate, β-hydroxybutyrate, and acetone
This process occurs in the liver and is regulated by enzymes such as β-ketoacyl-CoA transferase and β-hydroxybutyrate dehydrogenase
Ketone bodies are produced when the supply of carbohydrates is low and the body needs to use fat as its primary fuel source
Acetoacetate and D-β-hydroxybutyrate are transported by the blood to tissues other than the liver, where they are converted to acetyl-CoA and oxidized in the citric acid cycle