Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!

1. PURPOSE

  1. Lipids make up the final big category of metabolism, in addition to carbohydrates and amino acids

  2. Lipids are not only an efficient source of energy but also important for cell structure and signaling hormones

  3. This chapter prioritizes topics like cholesterol and lipid transport, which are especially relevant to cardiovascular disease

2. LIPID SYNTHESIS

  1. Recall acetyl-CoA from Chapter 5: Link between glycolysis and TCA cycle

  2. Acetyl-CoA is also the branch point toward lipid synthesis

  3. Overall, lipid synthesis can branch in 2 ways

    1. Fatty acid synthesis: Fatty acids (FAs), triglycerides (TGs) for fat storage

    2. Cholesterol synthesis: Important for cell membrane structure, steroid synthesis, and bile acid synthesis

  4. Each of these relates to common topics in other systems, such as atherosclerosis, hypercholesterolemia, and diabetes mellitus

3. FATTY ACID METABOLISM

  1. Much lower yield than most of the other side pathways we'll talk about

  2. Acetyl-CoA is the link between glycolysis and fatty acids

  3. Key synthesis steps

    1. Branch point is at citrate—citrate is leaving mitochondria via citrate shuttle for cytoplasm where it:

      • Regulates glycolysis by inhibiting PFK-1 (prevent excess glycolysis)

      • Converts back into acetyl-CoA for fatty acid synthesis

    2. Biotin (B7) is required for synthesis

    3. Synthesis occurs mainly where you would expect: Liver, and high-fat tissues that store lots of energy (adipose, mammary glands)

  4. Key breakdown steps

    1. Shuttle into the mitochondria to incorporate back into TCA cycle via carnitine shuttle

    2. Breakdown via β-oxidation to acetyl-CoA to enter directly into TCA cycle

    3. Even-numbered fatty acids cannot produce glucose (e.g., local energy source)

    4. Lipid metabolism in the liver is a major source of ketone bodies (see Chapter 9)

  5. Clinical: Fatty acids (like glycogen) are a major energy source especially for muscle cells

    1. Systemic primary carnitine deficiency—can't get long chain fatty acids into the mitochondria leading to accumulation

      • Weakness, hypotonia—lack of energy, especially during fasting

      • Hepatomegaly—liver function is impaired

      • Hypoketotic hypoglycemia—liver can't process fatty acids for ketogenesis during fasting; and tissues that could have used fatty acids or ketone bodies for energy end up using up too much glucose

    2. Medium-chain acyl-CoA dehydrogenase deficiency—later in the pathway; can't break down 8 to 10 carbon FAs into acetyl-CoA

      • Similar symptoms (hypoketotic hypoglycemia) but roughly speaking, more severe (infancy/early childhood)

      • Additionally: Vomiting, neurologic symptoms (brain uses ketones under certain conditions), and liver dysfunction

      • Treatment: Avoid lipolysis by regular food intake

Figure 8-1.

Overview of acetyl-CoA usage pathways.

Figure 8-2.

Fatty acid synthesis and breakdown.

4. CHOLESTEROL SYNTHESIS

  1. Synthesis takes place in the cytosol of virtually all tissues, though liver is a major source

  2. Carefully balanced with uptake through LDL receptors

  3. The cholesterol synthesis pathway can be distilled down to 3 steps for the ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.