MetabolismLecture 6 - Fatty Acid Breakdown

Question 1

What are the 2 most important enzymes in the Fatty Acid Synthesis/Breakdown pathway?

What is their function?

Answer 1

1. CPT1 (Carnitine Palmitoyl Transferase I)
   - convert Fatty Acyl CO A’s into Acetyl Co A
2. Acetyl Co A Carboxylase
   - convert Acetyl Co A into Fatty Acyl CO A

Question 2

When are fatty acids mobilized from adipose tissue TAGs into the liver? By what enzyme?

Answer 2

NEED FOR ATP

HSTL
- hormone-senitive triacylglycerol lipase

Question 3

What are the negative and positive hormonal regulators of HSTL?

Answer 3

negative = INSULIN

positive = EPINEPHRINE

• HSTL converts TAGS into glycerol for transport into the liver

Question 4

What are the fates of Released fatty acids?

What are the fates of released Glycerol?

Answer 4

Released fatty acids
Enter the circulation
Bind to albumin
Are carried to muscle, liver, etc.
For beta-oxidation and energy production

2. Released glycerol
   Is transported to liver and kidney
   Glycerol kinase phosphorylates glycerol to
   glycerol 3-phosphate, which can be used in gluconeogenesis

Question 5

What is the rate limiting enzyme in fatty acid biosynthesis?

What allosterically inhibits this enzyme in FA biosynthesis?

Answer 5

Acetyl Co A Carboxylase

• Fatty Acyl Co A’s (the starting material) can inhibit this enzyme

Question 6

How much ATP does the complete oxidation of palmitate yield?

Answer 6

106 ATP

Question 7

What is removed in each cycle of fatty acid degradation?

Answer 7

remove 2 carbon units
- FADH2, NADH and Acetyl Co A are produced

(8 Acetyl Co a, 7 NADH and 7 FADH2 are produced with the total oxidation of palmitate)

Question 8

Where are ketone bodies formed?

Answer 8

Liver mitochondria

Acyl CO A from Free Fatty Acids from Acetyl Co A and Acyl Glycerol

Question 9

What is the 1st ketone body?

What is the second ketone body?

Answer 9

1. Acetoacetate

2. B-HydroxyButyrate and Acetone formed from Acetoacetate spontaneously

Question 10

What is the rate limiting enzyme in Ketone Biosynthesis?
Where is it found?

What is the key enzyme for ketone utilization?
Where is it not found?

Answer 10

HMG - CoA Synthase
- FOUND ONLY IN THE LIVER

Acetoacetate: succinyl CoA Transferase enzyme

• NOT FOUND IN LIVER

Question 11

What does Acetoacetate Succinyl Co A do?

Answer 11

Convert Acetoacetate into Acetoacetyl Co A

Question 12

What tissues cannot use fatty acids as an energy source?

Answer 12

RBC
Brain
Nervous System
Adrenal Medulla
Lens

Question 13

What transports long chain fatty acids into the MITOCHONDRIAL MATRIX for B-oxidation?

Inhibition results in ? (2)

Answer 13

Carnitine

1. Inhibits Fatty Acid oxidation
2. Decreases ATP production

Question 14

What inhibits CPT1?

Answer 14

Malonyl Co A
- inhibits B-oxidation of fatty acids

(Malonyl Co A is the product of fatty acid biosynthesis)

Question 15

Deficiency in which enzyme results in SIDS?

Answer 15

MCAD

• medium chain Fatty Acid CoA Dehydrogenase

Question 16

Ketone bodies are synthesized from _____ in ____

Answer 16

1. Acetyl CO A

2. Mitochodnria

Question 17

What enzyme does the liver lack that prevents it from being able to USE ketone bodies?

What enzyme is present ONLY in the liver required for ketone biosynthesis?

Answer 17

THIOPRASE/ AcetoAcetate: SUccinyl CoA Transferase

HMG - CoA Synthase

Question 18

What hormones promote the BREAKDOWN and inhibit breakdown of TAG (Triacylglycerol)

What enzyme is responsible for converting TAG into Free Fatty Acids (FFA)?

Answer 18

Insulin - inhibits breakdown

EPinephrine - promotes breakdown

3. HST Lipase

Question 19

Describe how Glucagon & Einephrine stimulate the following:

1. Malonyl CO A
2. Acetyl CO A Carboxylase
3. CPT-1

Answer 19

1. INHIBIT fatty acid synthesis
2. INHIBIT
3. Stimulate - involved in formation of ketone bodies

Question 20

What is the only known inhibitor of CPT-1

Answer 20

Malonyl Co A

-, the product of fatty acid biosynthesis?

Question 21

Define the following for Acetyl - Co A Carboxylase:

1. Activator
2. Inhibitor
3. Hormonal Activator
4. Hormonal Inhibitor
5. Induces synthesis
6. Represses Enzyme synthesis

Comments?

Answer 21

Define the following for Acetyl - Co A Carboxylase:

1. Activator - CITRATE
2. Inhibitor - Long Chain Fatty Acyl Co A
3. Hormonal Activator - INSULIN
4. Hormonal Inhibitor - Glucagon/Epinephrine
5. Induces synthesis - High carb diet, fat free diet
6. Represses Enzyme synthesis - glucagon, epinephrine, high fat diet, fasting

Comments?
- REQUIRES BIOTIN,
synthesizes Malonyl Co A –> the inhibitor of CPT-1 (which converts fatty acyl into acetyl co A)

Question 22

What is the only known inhibitor of CPT -1?

Answer 22

Malonyl Co A

• CPT -1 is active unless Malonyl Co A is present

Question 23

What is the hormonal activator & inhibitor of HSTL?

2 for each

Answer 23

Activate:

• Epinephrine
• ACTH

Inhibit:

• insulin
• PGE

Question 24

What are the following 2 enzymes involved with?

1. Mitochondrial HMG - Co A
2. Acetoacetate: Succinyl CO A Transferase

Where is each found?

Answer 24

1. Mitochondrial HMG - Co A - LIVER
   - FORMS KETONE BODIES
2. Acetoacetate: Succinyl CO A Transferase - NOT LIVER
   - degrades Ketone Bodies

Where is each found?

Question 25

What activates 7-alpha-hydroxylase?

What is this enzyme involved with?

Answer 25

Cholesterol

• involved with BILE ACID formation

Question 26

Define the following for HMG - Co A REDUCTASE:

1. Inhibitor
2. Hormonal Activator
3. Hormonal Inhibitor

Comments?

Answer 26

1. Inhibitor
   - cholesterol
   - AMP
   - mevalonate
2. Hormonal Activator
   - insulin
3. Hormonal Inhibitor
   - glucagon

Question 27

What enzyme is involved with cholesterol esterification?

Answer 27

ACAT