Fatty Acid Oxidation

$$Even\ Chan\ Fatty\ Acid\ \beta - Oxidation\ Cycles = \left(\frac{Number\ Of\ Carbons}{2}\right) - 1$$

$$Odd\ Chan\ Fatty\ Acid\ \beta - Oxidation\ Cycles = \frac{Number\ Of\ Carbons - 3}{2}$$

$$\beta - Oxidation\ Cycles\ of\ C16:0= \left(\frac{16}{2}\right) - 1 = 7$$

$$\beta - Oxidation\ Cycles\ of\ C17:0 = \frac{17 - 3}{2} = 7$$

In a healthy person, if we labeled palmitate with $^{14}C$ the label shows up in glucose. This means that in the strictest sense of the word carbon atoms from a fat are incorporated into glucose. However, biochemists say, "You cannot make glucose from fat." How can you reconcile this apparent contradiction?

• you can make glucose that has the $^{14}C$ label from oxaloacetate

• The fatty acid is what is labeled

• Biochemists say you can't make glucose from fat

  • Theoretical Idea:

    • as you are breaking off acetyl-CoAs through $\beta$-oxidation , you are making a two carbon chain aka acetyl-CoA

    • When Acetyl-CoA enters into the TCA cycle with oxaloacetate , it combines to form citrate

      • However in steps 3 and 4 in TCA cycle we are loosing a carbon dioxide

    • The fatty acid contributed two carbons, but as it goes into the TCA cycle, two carbons are lost

  • The general idea is you can't make sugar by oxidizing fat because your "net" gain is zero carbons

• However,

  • The carbons that are lost as carbon dioxide are originally from oxaloacetate

  • So theoretically the carbons that came from acetyl-CoA could be turned into malate

    • malate can leave the mitochondria and can then be incorporated into glucose via gluconeogenesis.

Explain why glucose could be synthesized by metabolism of a C17 carbon fatty acid.

• Odd number fatty acid chains produce a propionyl-CoA
• propionyl-CoA gets converted into succinyl-CoA
• succinyl-CoA is then converted into oxaloacetate
• oxaloacetate is a substrate in gluconeogenesis

How many moles of glucose could theoretically be produced from one mole of C17:0 fatty acid?

• Glucose has 6 carbons
• The fatty acid gives only (1) propionyl-CoA
• 2 oxaloacetates are needed to make 1 glucose
• so 0.5 moles of glucose could be made from an odd chain fatty acid

Muscles are made up of cells called fast twitch and slow twitch. Fast twitch muscle generally appears white while slow twitch is brown due to additional mitochondria with their ETC proteins. Muscles burn fat all the time, especially slow twitch muscle. During periods of high demand fat can only be burned so fast because there are only so many copies of the protein and enzymes involved in ETC and oxidative phosphorylation. As a result, muscle burns glucose as we have many more copies of these enzymes. Explain why it is important that we have muscle cells that have many copies of the enzymes for glycolysis.

• You have different types of energy production for different types of muscle fibers
• Fast twitch fibers have very few mitochondria, therefore they rely on lactic acid fermentation.
• Slow twitch muscle fibers have mitochondria and can afford the time to run through glycolysis and ETC to generate energy.

Inhibitors of fatty acid degradation are used to relieve angina ( heart pain ) resulting from insufficient oxygen. Why does this make sense?

• If we prevent fatty acid degradation or fatty acid oxidation

  • we are not going to produce acetyl-CoA

    • $\therefore$ acetyl-CoA is not going to go through the TCA cycle to make NADH and FADH2

      • $\therefore$ its not "consuming" oxygen as the final electron acceptor in the ETC

• So it will provide more oxygen for the tissues because its not being consumed in ETC, but less energy

As you may know, camels don't need to consume much water, which is why they are used in desert conditions. Where does the water come from? Be sure to consider water as a reactant and product in your answer.

• The hydrocarbons stored as fats in the camel's hump are degraded and combined with oxygen to create $H_2O$

Briefly explain why the values calculated in ATP yield per carbon for glucose and palmitate using theoretical in vivo values for ATP production vs standard free energies differ.

• Standard energies and ATP yield energies are looking at in in vitro vs in vivo

• When you are looking in vivo :

  • we have to consider all the other molecules and concentrations in the system
  • you have to consider the concentration of ATP already inside the cell

• Standard free energies are just a theoretical in vitro value

• Intracellular concentrations are different than values used to calculate standard free energy

• ATP/ADP ratio in vivo is $10^8$ times larger than equilibrium ATP hydrolysis altered in reaction coupled to it

What do these results say about the relative efficiency of oxidizing carbohydrates and fats?

• No matter what, Fatty Acids are going to give you a higher percentage of ATP per carbon molecule
• Fats are much more efficient at giving us energy per carbon molecule

What is oxidized in each round of beta-oxidation?

The beta carbon of the acyl chain

What is reduced in each round of beta-oxidation?

NAD+ and FAD

Which of the following is the correct sequence of events (from start to finish) in cellular fatty acid oxidation?

Fatty acid activation → carnitine shuttle → beta-oxidation

• The three phases of fatty acid oxidation in the cell, in order, are fatty acid activation → carnitine shuttle → beta-oxidation (as seen in the figure below).
• Fatty acid activation takes the initial fatty acid in the cytosol and adds a CoA to yield acyl-CoA on the inner membrane.
• The acyl chain is then passed to a carnitine to become acyl-carnitine.
• Acyl-carnitine can enter the mitochondrial matrix where the acyl group is then committed to undergo complete oxidation via beta-oxidation and the citric acid cycle.
• Beta-oxidation partially oxidizes the acyl group, releasing some NADH and FADH2, and also releasing acetyl-CoA.
• Acetyl-CoA then goes to the citric acid cycle for final oxidation.

Which of these catalyzes the “committing-step” in fatty acid oxidation?

Carnitine shuttle

Things To Know

• Fatty Acid Oxidation

  • Free Fatty Acid Activation with CoA

    • Fatty acid activation takes the initial fatty acid in the cytosol and adds a CoA to yield acyl-CoA on the inner membrane.

  • Oxidation Occurs in Mitochondrial Matrix

  • Which Molecules Can Diffuse and Which Cannot:

    • Can Diffuse:

      • Nonpolar Molecules: $O_2$ , $CO_2$ , hydrocarbons with less than 10 carbons

    • Cannot Diffuse:

      • Polar molecules
      • Ions

  • Free Fatty Acid Transport

    • The acyl chain is then passed to a carnitine to become acyl-carnitine
    • Acyl-carnitine can enter the mitochondrial matrix where the acyl group is then committed to undergo complete oxidation via beta-oxidation and the citric acid cycle.

• Steps in Beta Oxidation

  • Steps:

    1. Dehydrogenation / Oxidation
    2. Hydration
    3. Dehydrogenation / Oxidation
    4. Thiolytic Cleavage

  • Products:

    • acetyl-CoA
    • NADH
    • FADH2

  • Similarities to Citric Acid Cycle:

    • Both Operate in Mitochondria
    • Both have Dehydrogenation , Hydration , then Dehydration Steps

  • Saturated vs Unsaturated

    • Melting Point ( Lowest to Highest )

      • Unsaturated < Cis Bonds < Trans Bonds < Saturated

  • Odd-Number Chain

    • Odd number fatty acid chains produce a propionyl-CoA
    • propionyl-CoA gets converted into succinyl-CoA
    • succinyl-CoA is then converted into oxaloacetate
    • oxaloacetate is a substrate in gluconeogenesis

• Energy Generation for All Possible Combinations

  • Fatty Acid's no matter what provide more energy per carbon than sugars