Chapter 24.3 Comprehensive Notes on Lipid Metabolism

Lipid Metabolism

Fats (triglycerides) are ingested or synthesized from carbohydrate precursors by adipocytes or hepatocytes.
Lipid metabolism involves oxidizing fatty acids for energy or synthesizing new lipids.
Lipid metabolism is linked to carbohydrate metabolism via acetyl CoA.

Triglycerides are broken down into smaller fatty acids and monoglycerides by pancreatic lipases in the intestine (Figure 24.11).
Bile salts emulsify fats to aid lipase activity.
Cholecystokinin (CCK) is released by intestinal cells in response to chyme:
- Stimulates pancreatic lipase release.
- Stimulates gallbladder contraction to release bile salts.
- Acts as a hunger suppressant in the brain.
Pancreatic lipases and bile salts break triglycerides into free fatty acids, which are absorbed across the intestinal membrane.
Inside intestinal cells, fatty acids are reassembled into triglycerides and packaged with cholesterol into chylomicrons (Figure 24.12).
Chylomicrons transport fats and cholesterol through the lymphatic and circulatory systems.
Chylomicrons leave enterocytes via exocytosis and enter the lymphatic system through lacteals.
From the lymphatic system, chylomicrons enter the circulatory system.
In circulation, chylomicrons are either transported to the liver or stored in adipocytes within adipose tissue.

Lipolysis is the process of breaking down triglycerides into fatty acids and glycerol in the cytoplasm.
Fatty acids are oxidized into acetyl CoA by β-oxidation and used in the Krebs cycle.
Glycerol enters the glycolysis pathway as DHAP (dihydroxyacetone phosphate).
Triglycerides yield more than twice the energy per unit mass compared to carbohydrates and proteins.

Occurs when glucose levels are low; triglycerides are converted into acetyl CoA for ATP production via aerobic respiration (Figure 24.13 & 24.14).
Fatty acids are converted into fatty acyl CoA molecules in the cytoplasm.
Fatty acyl CoA combines with carnitine to form fatty acyl carnitine, which transports fatty acids across the mitochondrial membrane.
Inside the mitochondrial matrix, fatty acyl carnitine is converted back into fatty acyl CoA.
Acetyl CoA enters the Krebs cycle to produce ATP.

Occurs when excessive acetyl CoA is produced from fatty acid oxidation and the Krebs cycle is overloaded (Figure 24.14).
Acetyl CoA is diverted to create ketone bodies, which serve as a fuel source when glucose levels are low.
Common in prolonged starvation or uncontrolled diabetes.
Excess acetyl CoA is converted into hydroxymethylglutaryl CoA (HMG CoA).
HMG CoA is a precursor of cholesterol and is converted into β-hydroxybutyrate, the primary ketone body in the blood.

Organs like the brain can use ketones as an alternative energy source when glucose is limited (Figure 24.15).
Ketones, when produced faster than used, are broken down into CO_2 and acetone.
Acetone is exhaled, causing a sweet, alcohol-like breath odor.
Excessive carbon dioxide can acidify the blood, leading to diabetic ketoacidosis.
β-hydroxybutyrate is oxidized to acetoacetate, releasing NADH.
Acetoacetate gains an HS-CoA molecule, forming acetoacetyl CoA.
Acetoacetyl CoA splits, yielding two acetyl CoA molecules that enter the Krebs cycle.

Occurs when glucose levels are plentiful; excess acetyl CoA is converted into fatty acids, triglycerides, cholesterol, steroids, and bile salts (Figure 24.16).
Takes place in the cytoplasm of adipocytes and hepatocytes.
Acetyl CoA, primarily from glycolysis, initiates lipogenesis.
Two-carbon atoms are added to acetyl CoA repeatedly until fatty acids reach the appropriate length.
ATP is consumed during this anabolic process.
Triglycerides and lipids are stored in adipose tissue until needed.

Acetyl CoA is created in the mitochondria but needed in the cytoplasm for lipogenesis.
Pyruvate is converted into oxaloacetate and acetyl CoA.
Oxaloacetate forms via pyruvate carboxylase, and acetyl CoA forms via pyruvate dehydrogenase.
Oxaloacetate and acetyl CoA combine to form citrate, which crosses the mitochondrial membrane into the cytoplasm.
In the cytoplasm, citrate is converted back into oxaloacetate and acetyl CoA.
Oxaloacetate is converted into malate and then into pyruvate.
Pyruvate crosses back into the mitochondria.
In the cytoplasm, acetyl CoA is converted into malonyl CoA, which is used to synthesize fatty acids.