Metabolism of Lipids

Metabolism of Lipids

• Covers key aspects such as digestion, degradation, biosynthesis, eicosanoids, ketone bodies, and cholesterol metabolism.

Digestion of Dietary Lipids

• Lipids aggregate in large droplets in watery environments, requiring emulsification to form smaller droplets for digestion.
• Mechanical breakdown occurs in the mouth and stomach primarily through chewing and churning.
• Lingual and gastric lipases contribute limited digestion of triacylglycerol before reaching the small intestine.
• Most lipid digestion occurs in the small intestine by pancreatic lipase, stimulated by the presence of fat.

Role of Bile in Digestion

• Bile acids, synthesized from cholesterol, play a crucial role in emulsifying fats.
• Bile salts, made from bile acids in the liver and stored in the gallbladder, are secreted in response to cholecystokinin, aiding in digestion.

Digestion and Absorption Processes

• Triacylglycerols (TG) are broken down into two free fatty acids and monoacylglycerol (2MG) by pancreatic lipases.
• Phospholipids are hydrolyzed to lysophospholipids by phospholipases A2.
• Cholesterol esters are converted to free cholesterol by cholesterol esterase.
• Absorbed lipid digestion products are re-esterified and packaged into chylomicrons for safe circulation.

Lipolysis: Breakdown of Triglycerides

• Lipolysis is the process that breaks down TG into glycerol and free fatty acids, occurring in the cytosol of adipose tissue.
• Hormone-sensitive lipase facilitates lipolysis and is stimulated by glucagon and epinephrine, while inhibited by insulin.

Fates of Lipolysis Products

• Glycerol enters the liver for glycolysis and gluconeogenesis due to lack of glycerol kinase in adipocytes.
• Free fatty acids can be re-esterified into TG or released into the bloodstream for transport and oxidation by tissues.

Fatty Acid Oxidation (β-Oxidation)

• Fatty acids must be activated to fatty acyl-CoA before entering the mitochondrial matrix for β-oxidation.
• This process repeats until the fatty acid is fully converted into acetyl-CoA, producing NADH and FADH2.

Energy Yield from β-Oxidation

• Each β-oxidation cycle generates acetyl-CoA, which is further utilized in the TCA cycle to produce ATP, CO2, and H2O.
• Odd-numbered fatty acids produce propionyl-CoA, which is converted into succinyl-CoA.

Ketone Body Metabolism

• Ketone bodies, produced in the liver, are transported to peripheral tissues and converted back into acetyl-CoA, generating NADH.
• Acetone is unable to revert to acetyl-CoA and is excreted in urine.

Cholesterol Biosynthesis

• Cholesterol synthesis initiates with acetyl-CoA, converted to HMG-CoA, and then to mevalonic acid through HMG-CoA reductase, the key regulatory step.
• The synthesis occurs in the cytosol and endoplasmic reticulum of tissues, primarily the liver, intestine, adrenal cortex, and reproductive organs.

Importance of Cholesterol

• Cholesterol is essential for cellular membrane structure and is found in all animal tissues.
• It also serves as a precursor for bile salts and steroid hormones, playing a vital role in physiological processes.