Lectures block - Fat & lipid metabolism

7 important questions on Lectures block - Fat & lipid metabolism

What can fatty acids be produced from, and how does this work?

- Palmitate (=fatty acid) can be synthesized from malonyl-CoA (which is synthesized from acetyl-CoA in the cytosol),
- and palmitate can be converted to other types of fatty acids.

What are the two things that can happen to palmitate after being produced from malonyl-CoA?

- If not further processed, it inhibits fatty acid synthesis.
- If further processed, the palmitate is transported in the form of triglycerides (packaged into VLDL), and fatty acid synthesis is not inhibited.

What is the effect of insulin and glucagon on fatty acid synthesis?

- When glucagon levels are high, the enzyme carboxylase (converts acetyl-CoA into malonyl-CoA!) is in an inactive form, which inhibits fatty acid synthesis.
- When insulin levels are high, fatty acid synthesis will just go on.
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When palmitate (or other fatty acids) are synthesized, they will be transported in the form of triglycerides by VLDL. What happens to the triglycerides?

The fatty acids are stored in muscle cells and adipose tissue, and the glycerol is recycled.

How is β-oxidation prevented when fatty acid synthesis is going on? In other words, how are futile cycles for fatty acids prevented?

- Malonyl-CoA (fatty acid synthesis) inhibits the conversion of acyl-CoA into acyl-carnitine,
- and this inhibition prevents the β-oxidation
(because carnitine is important in β-oxidation: for the transport of fatty acids into the mitochrondria)

What is the citric acid cycle regulated by, and how does this work (steps)?

By NADH levels,
1. If very few ATP molecules are used, there is less ADP available for the oxidation,
2. which causes the electron-transport chain to become blocked,
3. which causes a lot of NADH molecules to be unable to release their H+ and electrons,
4. Which causes the citric acid cycle to be blocked, because that needs NAD+.

In the previous question is explained why the citric acid cycle becomes blocked when very few ATP is used. How does the state in which few ATP is used lead to fatty acid synthesis (and thus storage instead of usage)?

- Acetyl-CoA will become abundant when the citric acid cycle is blocked,
- this causes pyruvate to convert into OAA instead of acetyl-CoA,
- OAA will convert into citrate,
- outside of the mitochondria the citrate will convert into acetyl-CoA,
- from which fatty acids will be synthesized.

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