Beta oxidation and Fatty Acid synthesis

Given a fatty acid, be able to calculate how many rounds of beta oxidation and the number of acetyl-CoA molecules produced when the entire fatty acid is catabolized. Be able to calculate how many molecules of ATP would be generated from the complete oxidation of a fatty acid in aerobic metabolism (TCA cycle, ETC, Ox. Phos.)

Where does beta oxidation take place in the cell?

It takes place in the mitochondrial matrix

How are fatty acids activated?

FA’s are activated by the addition of CoA in an ATP-dependent reaction

How many ATP are required to activate Fatty Acids?

2 ATP are required to activate 1 FA into a thioester

How are fatty acids transported from the cytoplasm to the mitochondrial matrix?

The carnitine shuttle system transfers fatty acyl-CoA from the cytosol into the mitochondria

How is carnitine related to fatty acid transport, the mitochondrial matrix, and the cytoplasm?

The carnitine shuttle system is required for moving fatty acids from the cytoplasm into the mitochondrial matrix

What’s the point of the acyl-carnitine shuttle?

it helps to convert fatty acyl-carnitine to fatty acyl-CoA (and back)

What products are generated in every round of beta oxidation?

• 1 FADH2

• 1 NADH

• 1 acetyl-CoA

• Fatty acyl-CoA (that gets 2c shorter each round)

How many molecules of ATP would be generated from the complete oxidation of a fatty acid in aerobic metabolism (TCA cycle, ETC, Oxidative Phosphorylation)?

106

Some organisms rely on their fat stores and beta oxidation to generate water, instead of just drinking it. How can fat be converted into water?

It can be converted into water through beta oxidation. Water is produced from the ETC when O2 molecules are added to OH groups.

Where does fatty acid synthesis occur in the cell?

It occurs in the cytoplasm and it is an energy intensive process

Citrate is a critical metabolite for fatty acid synthesis to occur. Besides its usual role in signaling a high energy state in the cell, what is it used for in this context?

In this context, it is exported to the cytoplasm. It is cleaved into acetyl-CoA and oxaloacetate which will be used later glycolysis

Fatty acid synthase is a monster enzyme that relies on the acyl carrier protein domain. What does this domain do?

It moves the substrate between active sites

Why is the acyl carrier protein domain so important in making fatty acid synthesis efficient?

It moves the substrate between active sites without lifting up and reattaching. It links the substrate covalently which helps to make the active site more reactive due to the cleaving of a thioester.

How is the acyl carrier protein domain similar to acetyl-CoA in beta oxidation?

What is the first committed step of fatty acid synthesis?

Acetyl-CoA carboxylase combines acetyl-CoA and bicarbonate in an ATP- and biotin-dependent reaction to make malonyl-CoA in the committed step

What is required for fatty acid synthesis to proceed after its committed step?

a malonyl-CoA enzyme is required after the committed step

ATP is needed in order to break down acetyl-CoA to malonyl-CoA

How is this committed step regulating enzyme regulated?

Acetyl-CoA carboxylase is regulated by its own structure. The dissociation of its filaments inhibits its activity

What is malonyl-CoA?

It is the product made by Acetyl-CoA carboxylase. It elongates fatty acid chains

What is malonyl-CoA used for

Malonyl is part of the fatty acid synthesis process. It allows for fatty acid synthesis to begin after acetyl-CoA has been added

Fatty acid synthesis requires a lot of ATP and NADPH. What are these molecules used for?

They are both used in palmitate FA synthesis (a major fatty acid in the body).

Fatty acid synthesis (and degradation) is regulated at the level of transport into and out of the mitochondria. How?

FA synthesis and degradation is regulated by the association and dissociation of filaments.

How does malonyl-CoA it inhibit beta oxidation?

High malonyl-CoA concentration inhibits carnitine acyl-transferase 1, which prevents transport into the mitochondria (where beta oxidation occurs)

What two things can inhibit acetyl-CoA?

1. phosphorylation in response to low energy conditions

2. long chain fatty acids preventing polymerization

What two things can activate acetyl-CoA?

1. Citrate allosterically promotes polymerization

2. dephosphorylation in response to insulin release

How many cycles does it take to make one molecule of C16:0 palmitate ((1/2)n -1)

7

((1/2)16 -1) = 8 -1 = 7

At what position do animals desaturate fatty acids?

At position C9

Where at in the cell does fatty acid elongation and desaturation take place at?

in the ER

Where in the cell does beta oxidation occur?

In the mitochondria

Where in the cell does fatty acid synthesis occur?

In the cytoplasm

Which hormone is responsible for activating FA synthesis?

insulin

Which hormones are responsible for activating beta oxidation?

epinephrine and glucagon

In order for FA’s to get into the mitochondria, they have to be transported in as what molecule?

acyl-carnitine

How does the committed step of FA synthesis affect beta oxidation?

It inhibits it because they are opposites