M&n Week 2: Lipid Metabolism In Fasting State

Front 1

When does fasting usually begin after a meal?

Back 1

2-4 hours after last meal

Front 2

Which hormones regulate the fasting state?

Back 2

1. Glucagon
2. Epinephrine
3. Cortisol

Front 3

Which hormone receptors are G-protein coupled receptors?

Back 3

1. Glucagon
2. Epinephrine

*Both result in increased levels of cAMP

Front 4

Which hormone involved in the fasting state responds the most quickly to changes in the environment (i.e. stress)?

Back 4

Epinephrine

Front 5

Which receptor does cortisol activate?

Back 5

Glucocorticoid receptor

Front 6

Adipose tissue in fasting and starvation is under the control of what hormone?

This hormone activates which enzyme?

Back 6

Epinephrine

*Activates hormone sensitive lipase

Front 7

What is the function of hormone sensitive lipase?

Back 7

Cleaves triacylglycerol, allowing free fatty acids and glycerol to be secreted from adipose stores

Front 8

Is hormone sensitive lipase active in its phosphorylated or dephosphorylated state?

Back 8

Phosphorylated

Front 9

What type of metabolic energy is resting skeletal muscle and cardiac muscle mostly reliant on during fasting?

What source of energy is used during active periods?

Back 9

Fatty acid oxidation is utilized for energy during rest
When metabolic demands increase, glycogen stores are used.

Front 10

What are the major metabolic pathways in fasting skeletal muscle?

Back 10

1. Fatty acid oxidation
2. Protein degradation--> amino acid gluconeogenic precursors

Front 11

What is the normal substrate for energy metabolism in the brain?

As fasting proceeds, what source of energy does the brain adapt to?

Back 11

Glucose is normal substrate

Brain adapts to using ketones after prolonged fasting

Front 12

What are the 2 mechanisms by which fatty acids are delivered to the liver, muscle, and heart during fasting?

Back 12

1. Nonesterified fatty acids are released from adipose tissue
2. Lipoprotein lipase releases fatty acids from lipoprotein particles

Front 13

What shuttle system is used for the transport of long-chain fatty acids into mitochondria?

Back 13

Carnitine shuttle

Front 14

What is the rate-limiting step of beta-oxidation?

Back 14

Carnitine shuttle

Front 15

Where does beta-oxidation take place?

Back 15

Mitochondrial matrix

Front 16

Describe the countertransport action of the carnitine shuttle.

Back 16

Fatty acyl-carnitine is transported into the mitochondrial matrix while carnitine is transported out

Front 17

Which tissue has the highest concentration of carnitine?

Back 17

Muscle tissue
(highest concentration of mitochondria and highest rate of beta-oxidation)

Front 18

What type of fatty acids utilize the carnitine shuttle for uptake into the mitochondria?

Back 18

Long chain fatty acids
(short and medium chain fatty acids are not trans-esterified to form fatty acyl CoA, so they are transported across the inner mitochondrial membrane without the need for the carnitine shuttle)

Front 19

What compound inhibits the carnitine shuttle?

Back 19

Malonyl-CoA

Front 20

How is beta-oxidation prevented under conditions where fatty acid synthesis is taking place?

Back 20

Malonyl-CoA is a potent inhibitor of beta-oxidation

Front 21

What is the 2-carbon unit that is released after each round of beta-oxidation?

Back 21

Acetyl-CoA

Front 22

What type of enzyme deficiency affects fatty acid oxidation in the liver?

Which metabolic pathway is impaired?

Back 22

Carnitine-palmitoyl transferase-1 deficiency

*Gluconeogenesis impaired
(Ketogenesis also impaired)

Front 23

Which enzyme deficiency occurs primarily in the muscle and heart?

What symptoms are accompanied by this deficiency?

Back 23

Carnitine-palmitoyl transferase-II deficiency

Symptoms:
1. Muscle weakness
2. Intolerance to fasting

Front 24

What is the most common inborn error of fatty acid metabolism?

Back 24

Medium-chain fatty acyl CoA dehydrogenase deficiency (MCAD)

Front 25

What is the result of MCAD on beta-oxidation?

Back 25

Beta-oxidation only proceeds until the fatty acyl chain has been shortened to medium acyl chain length.
*Partial oxidation products are excreted in urine as carnitine esters

Front 26

What type of diet are people with MCAD reliant on?

Back 26

High carbohydrate diet
(unable to tolerate long periods of fasting)

Front 27

T or F

Ketone bodies are produced only in the liver

Back 27

TRUE

Front 28

T or F

Ketone bodies can be used by most tissues, including the liver.

Back 28

FALSE

Ketone bodies are NOT used by the liver, but they are used in most other tissues

Front 29

List 3 ketone bodies.

Back 29

1. Acetoacetate
2. 3-hydroxy butyrate
3. Acetone

Front 30

Ketone bodies are synthesized from which initial compound?

Back 30

Acetyl-CoA

Front 31

At what point during fasting does ketogenesis begin?

Back 31

When the rate of beta-oxidation exceeds the capacity of the TCA cycle to fully oxidize acetyl-CoA
(excess amounts of acetyl-CoA present)

Front 32

During fasting, what is the major cataplerotic pathway?

Back 32

Gluconeogenesis

Front 33

In the fed state, what is the major cataplerotic pathway?

Back 33

De novo fatty acid synthesis

Front 34

How can amino acids be used for gluconeogenesis?

Back 34

Amino acids feed into the Krebs cycle to produce oxaloacetate, which can then be used for gluconeogenesis

Front 35

Where does the synthesis of ketone bodies take place?

Back 35

Mitochondrial matrix

Front 36

List 2 ways that acetoacetyl CoA can be produced? What is this substrate used for?

Back 36

1. Incomplete beta-oxidation
2. Condensation of 2 acetyl-CoAs (via thiolase)

*Acetoacetyl CoA is used for the synthesis of acetoacetate (ketogenesis)

Front 37

Describe the interconversion of ketone bodies

Back 37

Acetoacetate--->
1. Spontaneous decarboxylated in blood to acetone
2. Reduced to 3-hydroxybutyrate

Front 38

List 3 pathways that generate acetyl-CoA in the liver (which can then be used for ketogenesis).

Back 38

1. Glycolysis
2. Fatty acid oxidation
3. Amino acid catabolism

Front 39

During the fasted state, what compounds are released by adipose tissue?

What organs take up these compounds?

Back 39

1. Glycerol
2. Fatty acids

*Taken up by the liver, heart, and skeletal muscle

Front 40

During the fasted state, describe what energy sources are used by the brain?

Back 40

At first, glucose is used, but as fasting progresses, the brain adapts to using ketones

Front 41

During the fasting state, what compounds are absorbed by the liver?

What compounds are released from the liver?

Back 41

ABSORBED:
1. Glycerol (from adipose)
2. Fatty acids (from adipose)
3. Amino acids (from muscle)

RELEASED:
1. Glucose (gluconeogenesis, glycogenolysis)
2. Ketone bodies (ketogenesis)

Front 42

How does muscle switch from relying on carbohydrate metabolism as a source of energy during the fed state to fatty acid oxidation in the fasted state?

Back 42

Randle Cycle.

(Acetyl-CoA that results from glycolysis --> citrate --> malonyl-CoA which is a potent inhibitor of beta oxidation (binds to carnitine-palmitoyl transferase I). Malonyl-CoA is synthesized from the ACC complex. When the complex is phosphorylated, it is inactivated and can no longer synthesis malonyl-CoA. This releases the inhibition of beta-oxidation)

Front 43

When does the greatest flux through long chain fatty acid synthesis occur?

Back 43

After carbohydrate-rich meal

Front 44

When does the greatest flux through long-chain fatty acid degradation occur?

Back 44

Starvation

Front 45

What is the major tissue site of fatty acid synthesis?

Back 45

Liver

Front 46

What is the major site of fatty acid degradation?

Back 46

1. Muscle
2. Liver

Front 47

Fatty acid synthesis occurs in what part of the cell?

Back 47

Cytosol

Front 48

Fatty acid degradation occurs in what part of the cell?

Back 48

Mitochondria

Front 49

In fatty acid synthesis, what is the primary carrier of acetyl groups between the mitochondria and the cytosol?

Back 49

Citrate (mitochondria --> cytosol)

Front 50

In fatty acid degradation, what is the primary carrier of acetyl groups between the mitochondria and the cytosol?

Back 50

Carnitine (cytosol --> mitochondria)

Front 51

Which oxidation/reduction coenzyme is used in fatty acid synthesis?

Back 51

NADPH
(reduction)

Front 52

Which oxidation/reduction coenzymes are used in fatty acid degradation?

Back 52

1. NAD+
2. FAD
(oxidation)

Front 53

What is the two-carbon donor of fatty acid synthesis?

Back 53

Malonyl-CoA

Front 54

What is the two-carbon product of fatty acid degradation?

Back 54

Acetyl-CoA

Front 55

What compound activates fatty acid synthesis?

Back 55

Citrate

Front 56

What inhibits fatty acid synthesis?

Back 56

Long-chain fatty acyl CoA
(inhibits acetyl-CoA carboxylase)

Front 57

What inhibits fatty acid degradation?

Back 57

Malonyl-CoA
(inhibits carnitine palmitoyl transferase I)

Front 58

What is the product of long chain fatty acid synthesis?

Back 58

Palmitate

Front 59

What is the product of fatty acid degradation?

Back 59

Acetyl-CoA

Front 60

What treatment is best for a person with a muscle carnitine deficiency?1.

Back 60

1. Avoid prolonged fasts
2. Adopt high carb diet
3. Diet low in long-chain fatty acids
4. Supplement diet with medium chain fatty acids and carnitine