Lecture 12

Question 1

When someone loses weight, where does the fat go?

Answer 1

CO2

Question 2

How are fatty acids transported into the mitochondria, generally?

Answer 2

They are broken down first, moved in through transporters, then rebuilt

Question 3

How many carbons does each round of beta-oxidation remove?

Answer 3

Two

Question 4

How many rounds of beta-oxidation would a 16-carbon fatty acid go through?

Answer 4

7, because in the seventh cut, you split a four-C molecule into two 2-C molecules. No need for an 8th round

Question 5

Which product is the committed step in fatty acid synthesis and why?

Answer 5

Malonyl-CoA, because it is not used in beta-oxidation, only lipid biosynthesis. This helps prevent futile cycling.

Question 6

What are the general steps of fatty acid breakdown?

Answer 6

Dehydrogenation, hydration, dehydrogenation, and thiolytic cleavage

Question 7

What is the first detailed step of fatty acid breakdown (assume fatty acyl-CoA was made)?

Answer 7

acyl-CoA DH cleaves the bond between the alpha and beta carbons. A C=C bond is formed. FADH2 is made that donates e- to Q like Complex II

Question 8

What is the second detailed step of fatty acid breakdown?

Answer 8

Water is added and a hydroxyl hydrates beta carbon, thus getting rid of the C=C bond.

Question 9

What is the third detailed step of fatty acid breakdown?

Answer 9

DH oxidizes the beta carbon, yielding a carbonyl. NADH is produced that goes to NADH DH, then its e- enter the respiratory chain

Question 10

What is the fourth and final detailed step of fatty acid breakdown?

Answer 10

Thiolase adds CoA-SH to the fatty acid, which means the fatty acid gets cleaved 2-C halves, each with an acyl-CoA. 1 Acetyl-CoA is generated, which can then enter ketogenesis or the TCA cycle

Question 11

Where else do we see the DH, hydration, DH pattern?

Answer 11

TCA cycle with succinate and the oxidation of Leu

Question 12

Explain the beta-oxidation of a fatty acid with 1 cis-double bond

Answer 12

After beta-oxidation, an isomerase converts the cis-double bond to a trans-double bond, which then continues beta-oxidation and produces acetyl-CoA

Question 13

Explain the beta-oxidation of a fatty acid with 2 cis-double bonds

Answer 13

Several rounds of preliminary beta-oxidation. Then one cis-double bond converts into a trans double bond, which then gets moved over. A reductase gets rid of the other cis-double bond and the trans-double bond gets moved over to the alpha and beta carbons so that acetyl-CoA can be formed. NADP+ is generated in the reductase step.

Question 14

Explain beta-oxidation of a fatty acid with an odd-numbered chain length

Answer 14

Use propionyl-CoA carboxylase (which uses biotin, HCO3-, and ATP). Uses Co-B12 to make succinyl-CoA

Question 15

Are all ketone bodies ketones?

Answer 15

No

Question 16

Which are the 3 primary ketone bodies we make?

Answer 16

Acetone
D-beta-hydroxybutryate
Acetoacetate

Question 17

Why does the brain use ketone bodies as a fuel source when fasting?

Answer 17

Free fatty acids cannot pass through the blood brain barrier, but ketone bodies are able to

Question 18

What is the first step of ketogenesis?

Answer 18

A thiolase takes 2 acetyl-CoA and combines them to make acetoacetyl-CoA. A CoA-SH is released.

Question 19

What is the second step of ketogenesis?

Answer 19

HMG-CoA synthase adds 1 acetyl-CoA to acetoacetyl-CoA to generate HMG-CoA. One CoA-SH is released.

Question 20

What is the third step of ketogenesis?

Answer 20

HMG-CoA lyase converts HMG-CoA into acetoacetate

Question 21

What are the paths that acetoacetate can take?

Answer 21

It can decarboxylate to acetone, it can dehydrogenase to D-beta-hydroxybutryate, or it can enter the blood. Basically, it can convert to other types of ketone bodies.

Question 22

What happens when OAA levels are low?

Answer 22

Gluconeogenesis cannot occur, meaning the TCA cycle cannot occur either, so acetyl-CoA is used to make ketone bodies in the mitochondria

Question 23

How many acetyl-CoA molecules per ketone are generated outside the liver?

Answer 23

2 acetyl-CoA/ketone

Question 24

What happens when there are high blood concentrations of ketones?

Answer 24

Ketoacidosis. The blood acidifies and the TCA cycle is unable to regenerate intermediates

Question 25

Pros and cons of the keto diet?

Answer 25

Pros: lose weight
Cons: ketoacidosis, little vitamin intake, and little variety in diet (steak and eggs every day)

Question 26

From what molecules is malonyl-CoA made?

Answer 26

acetyl-CoA

Question 27

What is the first step of fatty acid biosynthesis (do not assume malonyl-CoA was made yet)?

Answer 27

Move acetyl-CoA from the matrix into the cytosol. Do this by first combining acetyl-CoA with OAA to make citrate, which goes through a transporter to cytosol. The citrate then reacts with ATP and CoA-SH to regenerate acetyl-CoA and ADP + Pi.

Question 28

What is the second step in FA biosynthesis (hint – acetyl-CoA just got moved to the cytosol)?

Answer 28

Make malonyl-CoA using acetyl-CoA carboxylase (similar to pyruvate carboxylase)

Question 29

How does acetyl-CoA carboxylase work?

Answer 29

The biotinyl arm takes a CO2 from HCO3- and moves it over to acetyl-CoA, which combine to form malonyl-CoA

Question 30

What is an allosteric activator of acetyl-CoA carboxylase? Allosteric inhibitor?

Answer 30

Activator: citrate
Inhibitor: palmitoyl-CoA (product downstream, comes after malonyl-CoA). Glucagon and epinephrine trigger phosphorylation AKA inactivation because you don’t want to make FA when you’re hungry

Question 31

Why does eating lots of fructose (i.e., high fructose corn syrup) lead to fat storage?

Answer 31

Citrate inhibits PFK-1, but fructose bypasses this step so it keeps forming citrate. This signals to the body that it’s full and should store fat.