Fatty Acid Degradation

Question 1

*Understand the nature of lipolysis.

Answer 1

Triacyclglycerols are stored in adipocytes as a liquid droplet.

Question 2

*Know the roles of glucagon and epinephrine in catabolism of triacyclglycerols.

Answer 2

Epinephrine and glucagon act through 7TM receptors, and stimulate the breakdown or lipolysis.
Protein kinase A phosphorylates perilipin, which is associated with lipid droplet and hormone-sensitive lipase.

Question 3

*Understand the fates of free fatty acids and glycerol in lipid metabolism.

Answer 3

the fates of free fatty acids and glycerol:

1. degradation of TAG to release fatty acids and glycerol into blood for transport to energy requiring tissues.
2. Activation of fatty acids and transport into mitochondria for oxidation
3. degradation of fatty acids to acetyl CoA for processing by citric acid cycle.

Question 4

*Be familiar with the role carnitine plays in transport of fatty acids.

Answer 4

Carnitine transports long fatty acid chains into the mitochondria for Beta oxidation (produce energy)

Question 5

*Understand the steps in Beta-Oxidation. What are the products after this process?

Answer 5

The four main steps in Beta-Oxidation: 
1. Oxidation (FAD)
2. Hydration (H20)
3. Oxidation (NAD+)
4. Thiolysis (CoA)- remove coA
products after one round of degradation: Acyl-Coa (-2 carbons) and Acetyl CoA.

Question 6

*Understand the additional steps needed for the degradation of unsaturated and odd numbered fatty acids.

Answer 6

answered in another question

Question 7

*What is the product of the final round of odd-fatty acid chain degradation? What is then product converted to?

Answer 7

Fatty acids with an odd number of carbon produce PROPIONYL CoA on final round.
Propionyl CoA is then converted to Succinyl CoA , which will then enter the citric acid cycle.

Question 8

*What are the three forms of ketone bodies? What are these ketone bodies formed from?

Answer 8

3 forms of ketone bodies:
1. Acetoacetate
2. 3-hydroxybutyrate- formed by reducing acetoacetate
3. acetone- formed by Spontaneous decarboxylation of acetoacetate
These ketone bodies are synthesized from acetyl coA in LIVER MITOCHONDRIA and secreted into the blood for use as fuel by some tissue such as heart muscle (2 acetyl CoA and H20 will form acetoacetate and 2 CoA)

Question 9

*Understand liver ketogenesis

Answer 9

Ketogenesis- the release of ketones into the blood stream by the liver for producing energy. This occurs when liver not able to uptake glucose, hence no Oxaloacetate, slow CAC and build up acetyl coA, leading to ketone body formation and low pH in blood.

Question 10

*Have an appreciation for why animals cannot convert fatty acids to glucose.

Answer 10

Fats are converted into acetyl CoA, which is then processed by citric acid cycle.
Oxaloacetate (CAC intermediate) is a precursor to gluocose.
Acetyl CoA derived from fats CANNOT lead to synthesis of oxaloacetate or GLUCOSE because although the two carbons enter the cycle (when acetyl condenses with oxaloacetate) the two carbons are LOST as CO2 before oxaloacetate is generated (cannot convert acetyl coa to pyruvate)

Question 11

*Understand the role of insulin in fatty acid metabolism.

Answer 11

Insulin normally stimulates the absorption of glucose by the liver (GLUT2).
Insulin also normally curtails (REDUCES) the FA MOBILIZATION by adipose tissue (prevent large amount of acetyl CoA).

Question 12

*What mechanism are faulty in diabetics?

Answer 12

Insulin does not work properly (ABSENCE OF INSULIN), leading to no glucose uptake and no synthesis of oxaloacetate. When oxaloacetate is low, the CAC will slow down, leading to release of free fatty acids. all energy taken from fats, leading to increase in Acetyl CoA, and ketone bodies forming. Blood pH will then drop (very acidic) and coma or death can occur.

Question 13

*Understand how the body handles starvation. What happens after several days of fasting? How does the brain get a source of fuel during fasting?

Answer 13

glucose is the predominant fuel for brain
During starvation, protein degradation is initially the source of carbons for gluconeogenesis in the liver. The glucose is then released into the blood for brain to use.
After several days of fasting, the brain begins to use ketone bodies as fuel
(ketone body will curtain protein degradation and prevent kidney failure).

Question 14

How many ATP does complete oxidation of Palmitate (c16) yield?

Answer 14

yields 106 molecules of ATP, (NET) after complete oxidation of palmitate (C16)

Question 15

What is another name for fatty acid degradation?

Answer 15

Beta-oxidation

Question 16

How are fatty acids stored? what are triacyclglycerols.
Describe where adipose tissue is located in the body
and the use of fatty acids in muscle?

Answer 16

Fatty acids are stored in adipose tissue as Triacyclglycerols (TAG), where fatty acids are linked to glycerol with ester linkages.
Adipose tissue is located throughout the body, with subcutaneous (below skin) and Visceral (around internal organs) deposits being most prominent.
Muscle also stores fatty acid for use in producing energy.

Question 17

Where does fatty acid degradation occur in the cell? Where does Fatty acid synthesis occur?

Answer 17

Fatty acid degradation occurs in MITOCHONDRIA.

Fatty acids synthesis- cytosol.

Question 18

What is the difference between the use of glucose and lipids in producing ATP?

Answer 18

Lipids and fatty acids are much better energy source than glucose.
Lipids- 106 ATP, while glucose will generate 6 ATP.

Question 19

How are Triacyclglycerols stored? What two hormones stimulate lipid breakdown?
How does protein kinase A play a role in this process?

Answer 19

TAG’s are stored in adipocytes as lipid droplets.
epinephrine and glucagon, through 7TM receptors stimulate lipid breakdown.
Protein Kinase A phosphorylates perilipin, which is associated with lipid droplet, and hormone-sensitive lipase.

Question 20

*How are fatty acids transported through the bloodstream?

Answer 20

Through fatty acid oxidation:

1. Fatty acid activation
2. Shuttled to the mitochondria
3. Acyl moeity degraded to two carbons at a time.

Question 21

*How are fatty acids transported through the bloodstream?

Answer 21

Through fatty acid oxidation:

1. Fatty acid are activated
2. Shuttled to the mitochondria
3. Acyl moeity degraded to two carbons at a time.

Question 22

What is the process of fatty acids being activated and what are the enzymes involved? what makes this reaction irreversible?

Answer 22

1. first, upon entering cytoplasm, fatty acids are activated by attachment to coenzyme A. This is the rate determining step, to convert acyl and HS-Coa to make Acyl coA.
   This reaction uses enzyme Acyl CoA synthetase.
   This two step reaction proceeds through an acyl adenylate intermediate (fatty acid react with ATP to form acyl adenylate and ppi)
   Reaction is IRREVERSIBLE due to action of pyrophosphatase (ppi and H20 > 2 pi phosphate)

Question 23

What happens to the fatty acid after being activated by linkage to CoA? What is this reaction catalyzed by?
What structure transports the acyl carnitine?

Answer 23

After being activated by linkage to CoA, the fatty acid (acyl coA) is transferred to CARNITINE, for transport into the mitochondria.
The reaction is catalyzed by carnitine acyltransferase I.
A TRANSLOCASE transports the acyl carnitine into the mitochondria.

Question 24

What enzyme transfers the fatty acid back to coA in the mitochondria? what is the result of this reaction?

Answer 24

In the mitochondria, the CARNITINE TRANSFERASE II transfers the fatty acid to the CoA (remove carnitine). The fatty acyl coA is now ready to be degraded.

Question 25

How many molecules of ATP does complete oxidation of palmitate yield?

Answer 25

Complete oxidation of PALMITATE (16 c) yields 106 ATP (net)

Question 26

What are the 4 steps to fatty acid degradation?

Answer 26

The fours steps for fatty acid degradation:
1. OXIDATION of Beta carbon, catalyzed by acyl CoA dehydrogenase, generating trans-delta^2 enoyl coA and Fadh2
2 HYDRATION of trans-delta^2 enoyl coA by enoyl coA hydratase yields I-3 hydroxyacyl CoA.
3. Oxidation of I-3 hydroxyacyl CoA DH generates 3-ketoacyl CoA and NADH.
4. CLEAVAGE (or thiolysis) of 3-ketoacyl CoA by thiolase forms acetyl CoA and a fatty acid chain two carbons shorter.

Question 27

What regulates the ability of fatty acids to be degraded?

Answer 27

The activity of lipases.

Question 28

What enzymes are needed specifically for oxidation of Unsaturated acids and why?

Answer 28

An ISOMERASE and REDUCATASE are required for the oxidation of UNSATURATED fatty acids.

Question 29

Explain why Beta-oxidation cannot degrade Unsaturated fatty acids. How are monounsaturated fatty acids oxidized?

Answer 29

Beta oxidation cannot degrade unsaturated FA’s because when monounsaturated FA’s are degraded, cis-delta 3 enoyl CoA is formed, which cannot be processed by acyl CoA Dehydrogenase.
To be oxidized, monounsaturated FA’s use Cis-delta^3 enoyl CoA to convert the double bond into TRANS-delta^2-enoyl CoA (normal substrate for Beta oxidation).

Question 30

What is the normal substrate for Beta oxidation (can be processed by Acyl CoA DH) ?

Answer 30

The normal substrate is Trans-delta^2 enoyl CoA.

Question 31

What happens when polyunsaturated fatty acids are degraded by Beta-Oxidation? What enzymes are required?

Answer 31

When polyunsaturated FA’s are degraded by B-oxidation 2,4-Dienoyl CoA is generated, but cannot be processed by normal enzymes.
Hence a Cis-delta^3-enoyl CoA isomerase is needed and a REDUCTASE also needed.
2, 4 Dienoyl CoA will be converted into trans-delta^3 enoyl CoA by 2,4-dienoyl CoA reductase. The ISOMERASE then converts the product to trans-delta^enoyl CoA (normal substrate)

Question 32

Differentiate between the enzymes used for unsaturated fatty acids with Odd number of double bonds compare to even number of double bonds.

Answer 32

unsaturated fatty acids:

• ODD number of double bonds: require ONLY ISOMERASE
• EVEN number of double bonds: require both ISOMERASE and REDUCTASE

Question 33

What is the product formed in last Thiolysis reaction for Beta oxidation of FA’s with odd numbers? What this product later lead to?

Answer 33

The products is propionyl CoA.
Propionyl Coa will then form succinyl CoA.
Propionyl carboxylase (biotin enzyme) will add a carbon to propionyl CoA to form methylmalonyl CoA.
Then methylmalonyl CoA will form Succinyl CoA (CAC component) by methylmalonyl CoA mutase (Vitamin B12 requiring enzyme).

Question 34

How can you use ketone bodies to generate molecules of acetyl coA?

Answer 34

In tissues using ketone bodies, 3-hydroxybutyrate is oxidized to acetoacetate. The acetoacetate is ultimately metabolized to 2 molecules of acetyl CoA.

Question 35

What enzyme does the liver lack in terms for ketone body process?

Answer 35

Liver cells lack CoA transferase (that converts acetoacetate to acetoacetyl CoA).

Question 36

What physiological functions in the body may use acetoacetate over glucose? What do high levels of acetoacetate in blood indicate?

Answer 36

Normal fuels for respiration, heart muscle and renal cortex may use acetoacetate over glucose.
High levels of acetoacetate in blood indicate ABUNDANCE of acetyl CoA units, which leads to a decrease in lipolysis (breakdown of lipids).

Question 37

How can ketogenic diets provide benefits for children’s health?

Answer 37

Ketogenic diets, RICH in FATS, low in CARBS, but with adequate PROTEINS, lead to formation of substantial amount of ketone bodies.
For reasons not established, these diets REDUCE the SEIZURES in children suffering from drug-resistant epilepsy.

Question 38

How can ketone bodies lead to acidosis? when can this scenario occur.

Answer 38

Ketone bodies are moderately strong acids, and excess production of these ketone bodies can lead to acidosis.
An overproduction of ketone bodies can occur when diabetes (condition from lack of insulin function) is untreated, leading to acidosis,. This is called diabetic ketoses.

Question 39

Explain the mechanism behind the diabetic ketosis, and how it can turn lethal in patients.

Answer 39

If insulin is absent or not functioning, glucose CANNOT enter the cells. All energy must be derived from fats, leading to the production of acetly CoA.
Acetyl CoA will start to BUILD UP because oxaloacetate, which can be generated from Glucose is NOT available to replenish Citric Acid Cycle (result: ketoacidosis, drop in blood pH, and DEHYDRATION)
Also, FA RELEASE from adipose tissue is ENHANCED in the absence of insulin function.

Question 40

What is the predominant source of fuel for brain?

Answer 40

GLUCOSE is predominant source of fuel for brain.

Question 41

What is the largest energy store in the body?

Answer 41

FATS- largest energy store in the body.

Question 42

What occurs in metabolism after an overnight fast (postabsorptive state) ? what are substrates for gluconeogenesis and how are they used for lipid metabolism?

Answer 42

After an overnight fast (absorptive state), liver metabolism changes from glucose utilization to glucose production (through gluconeogenesis stimulating by glucagon).
Glucagon also stimulates glycogenolysis and inhibits glycolysis. The substrates for gluconeogenesis are ALANINE, LACTATE and GLYCEROL.
alanine and lactate are transported to liver from muscle.
glucose uptake by muscle and adipose tissue decreases, and degradation of TAG (lipolysis) and FA oxidation are stimulated , providing energy.