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5-3-4. Lipid Metabolism

Learning Objectives

  • Explain how energy can be derived from fat
  • Explain the purpose and process of ketogenesis
  • Describe the process of ketone body oxidation
  • Explain the purpose and the process of lipogenesis

Fats (or triglycerides) within the body are ingested as food or synthesized by adipocytes or hepatocytes from carbohydrate precursors (Figure 1). Lipid metabolism entails the oxidation of fatty acids to either generate energy or synthesize new lipids from smaller constituent molecules. Lipid metabolism is associated with carbohydrate metabolism, as products of glucose (such as acetyl CoA) can be converted into lipids.

Figure 1: A triglyceride molecule (a) breaks down into a monoglyceride (b).

Lipid metabolism begins in the intestine where ingested triglycerides are broken down into smaller chain fatty acids and subsequently into monoglyceride molecules by pancreatic lipases. When food reaches the small intestine in the form of chyme, a digestive hormone called cholecystokinin (CCK) is released by intestinal cells. CCK stimulates the release of pancreatic lipase from the pancreas and the contraction of the gallbladder to release stored bile salts. CCK also acts as a hunger suppressant.

Pancreatic lipases and bile salts break down triglycerides into free fatty acids, which are transported across the intestinal membrane and recombined into triglycerides. These are packaged with cholesterol in vesicles called chylomicrons (Figure 2), enabling fats to move through the lymphatic and circulatory systems.

Figure 2: Chylomicrons contain triglycerides, cholesterol, and apolipoproteins for lipid transport.

Lipolysis

To obtain energy from fat, triglycerides are broken down by hydrolysis into fatty acids and glycerol. This process, called lipolysis, takes place in the cytoplasm. Fatty acids undergo β-oxidation to form acetyl CoA, which enters the Krebs cycle. Glycerol enters glycolysis as DHAP. Fat yields more than twice the energy per unit mass compared to carbohydrates or proteins.

Figure 3: Fatty acids are oxidized to acetyl CoA and used for energy when glucose is low.

Ketogenesis

When excessive acetyl CoA accumulates and the Krebs cycle cannot process it all, the acetyl CoA is converted into ketone bodies. These serve as alternative fuel sources during starvation or uncontrolled diabetes. Excess acetyl CoA becomes hydroxymethylglutaryl CoA (HMG CoA), a precursor of cholesterol, which converts into β-hydroxybutyrate (Figure 4).

Figure 4: Excess acetyl CoA is converted into β-hydroxybutyrate, the main ketone body.

Ketone Body Oxidation

Organs such as the brain can use ketones for energy. When ketones are overproduced, they are broken into CO₂ and acetone, leading to a sweet smell on the breath and possible ketoacidosis. β-hydroxybutyrate is oxidized to acetoacetate, forming acetoacetyl CoA, which then yields two acetyl CoA molecules that enter the Krebs cycle (Figure 5).

Figure 5: Ketone bodies oxidize to acetyl CoA, which enters the Krebs cycle.

Lipogenesis

When glucose is abundant, excess acetyl CoA is converted into fatty acids, triglycerides, and cholesterol in a process called lipogenesis. This occurs in the cytoplasm of liver and fat cells. Pyruvate is converted to oxaloacetate and acetyl CoA, forming citrate that crosses into the cytoplasm and regenerates acetyl CoA for fatty acid synthesis (Figure 6).

Figure 6: Lipids can follow different metabolic pathways. Glycerol and fatty acids follow separate routes.

Chapter Review

Lipids are sourced from the diet, adipose tissue, or synthesized in the liver. Dietary fats are digested into monoglycerides and fatty acids, absorbed, and reassembled into triglycerides for transport. Fatty acids are oxidized into acetyl CoA for ATP production. Excess acetyl CoA leads to ketone formation or lipid synthesis.

Review Questions

  1. Lipids in the diet can be ________.
    Answer: all of the above
  2. The gallbladder provides ________ that aid(s) in lipid transport.
    Answer: bile salts
  3. Triglycerides are transported by chylomicrons because ________.
    Answer: they cannot move easily in water-based blood
  4. Which molecule produces the most ATP?
    Answer: triglycerides
  5. Which molecules can enter the Krebs cycle?
    Answer: acetyl CoA
  6. Acetyl CoA can be converted to all of the following except ________.
    Answer: polysaccharides

Critical Thinking Questions

  1. Discuss how carbohydrates can be stored as fat.
  2. If a diabetic’s breath smells like alcohol, what could this mean?

Glossary

β-hydroxybutyrate
Primary ketone body produced in the body.
β-oxidation
Fatty acid oxidation process producing acetyl CoA.
Bile salts
Salts released by the liver that emulsify fats for digestion.
Cholecystokinin (CCK)
Hormone that stimulates lipase release and bile salt secretion.
Chylomicrons
Vesicles that transport triglycerides and cholesterol through the body.
Hydroxymethylglutaryl CoA (HMG CoA)
Intermediate molecule in ketone body and cholesterol synthesis.
Ketone bodies
Alternative energy molecules produced during low glucose availability.
Lipogenesis
Formation of lipids in the liver or adipose tissue.
Lipolysis
Breakdown of triglycerides into glycerol and fatty acids.
Triglycerides
Fats made of three fatty acid chains bound to a glycerol molecule.