Fatty Acid Oxidation & Ketone Body Synthesis

Question 1

What enzyme regulates lipolysis? What hormones regulate the enzyme?

Answer 1

Hormone-sensitive lipase regulated by glucagon and epinephrine

Question 2

What ketone body provides the most energy?

Answer 2

3-Hydroxybutryate

Question 3

Where does long-chain FA metabolism begin? How do these FA enter the mitochondria?

Answer 3

Activation in the cytosol and then transported to the mitochondrial matrix by the carnitine shuttle

Question 4

An individual is unable to complete beta-oxidation, but is still oxidizing FAs. How is this possible?

Answer 4

Omega oxidation is a minor pathway for FA metabolism. Activity increases when beta-oxidation is deficient. Omega oxidation takes place in the ER of liver and kidney cells.

Question 5

How are ketone bodies synthesized? Be sure to include all relevant intermediates and enzymes.

Answer 5

Ketone bodies are synthesized in the mitochondria of liver cells.

2 acetyl CoA are combined by the acetoacetyl-CoA Thiolase to generate acetoacetyl CoA.

Acetoacetyl CoA is combined with another acetyl CoA by the HMG-CoA Mutase to produce HMG-CoA.

HMG-CoA is lysed by the HMG-CoA lyase to produce Acetoacetate.

Acetoacetate can be broken down to form acetone and 3-Hydroxybutryate by the B-Hydroxybutryate Dehydrogenase.

Question 6

How does beta-oxidation of odd-chain FAs differ from even-chain FAs?

Answer 6

The FA undergoes regular beta-oxidation, however, the final round produces 1 Acetyl CoA and 1 3C Propionyl CoA. Propionyl CoA is converted to Succinyl CoA and enters TCA.

Question 7

The liver releases KBs into the blood. What tissues utilize KBs for energy?

Answer 7

Skeletal muscle, heart muscle, and the brain (in periods of prolonged starvation) utilize KBs for energy. The liver lacks the enzymes necessary to use KBs for energy.

Question 8

What enzymes catalyze lipolysis in adipose tissue?

Answer 8

Adipose triglyceride lipase
Hormone-sensitive lipase
Monoacylglycerol lipase

Question 9

Very long-chain FAs are oxidized in peroxisomes. How does this process take place? What are the products?

Answer 9

Oxidation of VLCFAs is mediated by flavoprotein dehydrogenase that produce Octanoyl CoA, Propionyl CoA, & Acetyl CoA. These molecules are then transported to the mitochondria for further oxidation. This process is less efficient that beta-oxidation in the mitochondria and produces heat rather than ATP.

Question 10

Very long-chain FAs are oxidized in peroxisomes. How does this process take place? What are the products?

Answer 10

Oxidation of VLCFAs is mediated by flavoprotein dehydrogenase that produce Octanoyl CoA, Propionyl CoA, & Acetyl CoA. These molecules are then transported to the mitochondria for further oxidation. This process is less efficient than beta-oxidation in the mitochondria and produces heat rather than ATP.

Question 11

What enzymes are involved in beta-oxidation of an activated fatty acid (Fatty Acyl CoA)?

Answer 11

Acyl CoA Dehydrogenase
Enol CoA Hydratase
Hydroxyacyl CoA Dehydrogenase
Keto-Acid Thiolase

Question 12

Long-chain fatty acids must be activated in the cytosol before metabolism begins. What enzyme activates the FA? How is the FA activated

Answer 12

LCFA Thiokinase / Acyl CoA Synthase add a CoA to the FA

Question 13

True/False. Hormone-sensitive lipase is active when phosphorylated.

Answer 13

True. Glucagon stimulates phosphorylation of hormone-sensitive lipase.

Question 14

What amino acids are exclusively ketogenic?

Answer 14

Lysine & Leucine

Question 15

What are the three ketone bodies produced by the liver?

Answer 15

Acetoacetate, 3-Hydroxybutryate, Acetone

Question 16

True/False. Glycolysis produces more energy than beta-oxidation.

Answer 16

False. Beta oxidation produces numerous acetyl CoA for TCA, thus much more energy than glycolysis.

Question 17

What hormone induces KB synthesis? What enzyme is induced?

Answer 17

Glucagon induces the HMG-CoA Synthase

Question 18

What is unique about oxidation of branched FAs in peroxisomes?

Answer 18

Branches FAs must undergo Beta-alpha-oxidation. Alpha oxidation only takes place in peroxisomes.

Question 19

Where are very long-chain FAs metabolized?

Answer 19

Peroxisome

Question 20

How are short and medium-chain FAs transported to the mitochondrial matrix for metabolism?

Answer 20

Diffusion

Question 21

How is Propionyl CoA converted to Succinyl CoA?

Answer 21

Propionyl CoA is converted to D-methylmalonyl CoA by the Propionyl CoA Carboxylase & Biotin.

D-methylmalonyl CoA is epimerized to L-methylmalonyl CoA by the Methylmalonyl CoA Epimerase.

L-methylmalonyl CoA is converted to Succinyl CoA by the Methylmonyl CoA Mutase & Vitamin B12.

Question 22

How are free FAs transported in the blood?

Answer 22

Attached to albumin

Question 23

What molecule inhibits CAT-I?

Answer 23

Malonyl CoA - Intermediate of FA synthesis that prevents futile cycles

Question 24

What is the product of one round of beta-oxidation?

Answer 24

Beta oxidation produces 2 Acetyl CoA molecule and a FA that is two carbons shorter

Question 25

How is Fatty Acyl CoA transported from the cytosol into the matrix? Be sure to include any relevant substrates and enzymes.

Answer 25

Fatty Acyl CoA can diffuse from the cytosol through the outer membrane into the intermembrane space of the mitochondria. Fatty Acyl CoA is then converted to Acyl Carnitine by Carnitine Acyltransferase-I (CAT-I), which can move from the inner membrane into the matrix. CAT-II then converts Acyl Carnitine back to Fatty Acyl CoA

Question 26

How are ketone bodies synthesized?

Answer 26

Ketone bodies are synthesized in the mitochondria of liver cells.