Fatty Acid Oxidation & Ketones

Question 1

How does unsaturated fatty acid oxidation differ from regular beta oxidation?

Answer 1

Unsaturated fatty acids must first go through step/reactions that reduce the double bonds before beta oxidation can take place.

Question 2

How many molecules of NADH and FADH2 (total number) would be formed from the beta oxidation of a C10 fatty acid?

Answer 2

Beta oxidation: oxidative removal of successive 2 carbon units. Each round yields 1 NADH and 1 FADH2.

(10-2) / 2 = 4 each

8 total

Question 3

Describe the process of getting fatty acids into mitochondria for beta oxidation.

Answer 3

FAs must first be activated by cytosolic acyl-CoA

Then bind to carnitine on the outer mitochondrial membrane, shuttled through the inner space and through the carnitine transport protein on the inner mitochondrial membrane.

Once in the matrix, the mitochondrial acetyl-CoA removes FA from carnitine.

Question 4

Identify the three ketone bodies. Where do their carbons come from?

Answer 4

Acetone, acetoacetate, D-beta-hydroxybutyrate

All carbons come from acetyl-CoA

Question 5

List reasons why ketogenesis is important.

Answer 5

Spares glucose
Less toxic than FAs
More soluble
Bypass regulation in mitochondria
Diagnostics for diabetes
Regulate glycolysis in adipocytes

Question 6

Which enzyme in b-oxidation in chain length specific?

Answer 6

Acyl-CoA dehydrogenase.
Short (C4-C6)
Medium (C6-C10)
Long (> or = C11)

Question 7

What must happen to a FA prior to oxidation?

Answer 7

FA must be activated to fatty acyl-CoA.

Question 8

What are the three enzymes needed to transport fatty acyl-CoA into the mitochondria?

Answer 8

CAT I (carnitine acyltransferase I)
CAT II (carnitine acyltransferase II)
Carnitine transport protein

Question 9

What is the driving force in the formation of acyl-CoA from a fatty acid?

Answer 9

Hydrolysis of PPi

Question 10

Why is the reformation of acyl-CoA necessary after acyl-carnitate is transported into the mitochondria during beta-oxidation?

Answer 10

Because we can’t metabolize acyl-carnitate.

Question 11

What are the four reactions types in beta-oxidation?

Answer 11

Dehydrogenation (acyl-CoA dehydrogenase)

Hydration (enoyl-CoA hydratase)

Dehydrogenation (L-3-hydroxyacyl-CoA dehydrogenase)

Thiolytic cleavage (Thiolase)

Question 12

What are the products formed from the thiolase reaction in beta-oxidation?

Answer 12

Acetyl-CoA and Fatty acyl-CoA (now 2 carbons shorter)

Question 13

How does odd chain fatty acid metabolism differ from even chain fatty acid metabolism?

Answer 13

Odd-chain FAs are oxidized by the normal mitochondrial beta-oxidation process.

However, the last thiolytic cleavage step produces one molecule of acetyl-CoA and one molecule of propionyl-CoA.

Question 14

What is the required cofactor for the mutase reaction of odd-chain fatty acid metabolism?

Answer 14

Bitamin B12

Question 15

What is hydrogen’s involvement in the mutase reaction of ocfa metabolism?

Answer 15

Hydrogen pulled from substrate and placed on deoxyadenisine. It does NOT mix with solvent.
This is due to acidic a-hydrogen and the good carbanion leaving group.

Question 16

What is the energy yield from palmitate? (reaction)

Answer 16

Palmitoyl-CoA + 7FAD + 7(NAD+) + 7CoA + 7water ——-> 8AcCoA + 7FADH2 + 7NADH + 7(H+)

Question 17

What are the fates of acyl-CoA?

Answer 17

B-oxidation or conversion to triglycerides/phospholipids.

Question 18

What effect does malonyl-CoA have on the regulation of FA oxidation?

Answer 18

Malonyl-CoA is an intermediate in FA synthesis.

Inhibits CAT I, preventing FA entry into mitochondria.

Question 19

What is the parent compound of the three ketone bodies?

Answer 19

Acetoacetyl-CoA which is formed from condensing two acetyl-CoA molecules (via thiolase).

Question 20

T or F: Ketone bodies are water soluble equivalents of FAs.

Answer 20

T

Question 21

What are the roles of HMG-CoA synthase and HMG-CoA lyase?

Answer 21

Synthase: Add an extra AcCoA to acetoacetyl-CoA
Lyase: Cleaves off AcCoA to form acetoacetate

Question 22

What are the fates of acetoacetate?

Answer 22

Can decarboxylate or reduce

Question 23

How would a build up of AcCoA affect blood pH?

Answer 23

Blood pH would lower leading to acidosis