Biochemistry Chapter 27: Fatty Acid Degradation

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Questions and Answers

What role does 3-ketothiolase play in fatty acid oxidation?

It forms acetoacetate from acetyl CoA.

It helps the liver take on a metabolic load. (correct)

It releases free CoA during ketone production.

It facilitates the conversion of ketones into fatty acids.

Which enzyme is involved in the spontaneous decarboxylation of acetoacetate?

Hydroxymethylglutaryl CoA synthase

D-3-hydroxybutyrate dehydrogenase

3-ketothiolase (correct)

Hydroxymethylglutaryl CoA cleavage enzyme

What happens to acetyl CoA when fatty acid oxidation in the liver exceeds its utilization?

It is stored as glycogen.

It is transformed into carbohydrates.

It contributes to ketone body production. (correct)

It is converted back to fatty acids.

How do ketones provide energy for tissues?

By converting back into acetyl CoA. Signup and view all the answers

What is a characteristic of ketogenic diets?

Rich in fats and low in carbohydrates with adequate proteins. Signup and view all the answers

What can result from diabetic ketosis?

Rapid increase in ketones due to low insulin. Signup and view all the answers

What occurs as tissues adapt during starvation?

Increase in the ability to metabolize ketones. Signup and view all the answers

What effect do ketogenic diets have on drug-resistant epilepsy?

They can reduce the number of seizures. Signup and view all the answers

What is a consequence of excess acetyl CoA in the TCA cycle?

Shunting of acetyl CoA to ketones. Signup and view all the answers

What may alter neurotransmitter levels in response to ketogenic diets?

Alterations in intestinal flora. Signup and view all the answers

What initiates the breakdown of triacylglycerols to release fatty acids from adipose tissue?

Epinephrine or glucagon Signup and view all the answers

What is the role of perilipin in the mobilization of fatty acids from triacylglycerols?

It organizes the fat droplet for accessibility. Signup and view all the answers

During the process of lipolysis, which enzyme is primarily responsible for the removal of the first fatty acid from triacylglycerols?

Adipose triglyceride lipase (ATGL) Signup and view all the answers

What is the end product of fatty acid degradation that enters the citric acid cycle?

Acetyl CoA Signup and view all the answers

In Chanarin-Dorfmam syndrome, which of the following components is defective, leading to impaired triacylglycerol hydrolyzation?

Coactivator for ATGL Signup and view all the answers

What type of lipolysis occurs when the body is in a state of low blood glucose or during a stress response?

Hormone-sensitive lipolysis Signup and view all the answers

Which of the following statements about triacylglycerols is correct?

They have a high storage capacity and are highly reduced. Signup and view all the answers

Which lipase is responsible for removing the second fatty acid during triacylglycerol hydrolysis?

Hormone-sensitive lipase Signup and view all the answers

From where is triacylglycerol primarily mobilized in the body for energy?

Adipose tissue Signup and view all the answers

What is released alongside glycerol during the degradation of triacylglycerols?

Three fatty acids Signup and view all the answers

What happens during each round of β-oxidation of fatty acids?

1 acetyl CoA is generated, and the fatty acyl-CoA decreases by 2 carbons. Signup and view all the answers

What is the net energy yield when palmitic acid undergoes complete oxidation?

106 ATP considering both β-oxidation and TCA cycle. Signup and view all the answers

Which of the following accurately describes the final round of β-oxidation for a 4-carbon fatty acyl-CoA?

It results in one FADH2 and one NADH. Signup and view all the answers

What is the effect of C=C bonds in unsaturated fatty acids on β-oxidation?

They result in the loss of one FADH2 generation. Signup and view all the answers

How does the body adapt to prolonged starvation conditions?

Fatty acid oxidation increases and ketone body usage begins in the brain. Signup and view all the answers

In the oxidation of unsaturated fats, what role do isomerases and reductases play?

Isomerases rearrange double bonds to appropriate locations and reductases oxidize through NADPH. Signup and view all the answers

What are ketone bodies primarily formed from in the body?

Fatty acids through β-oxidation processes in the liver. Signup and view all the answers

What is the primary consequence of gluconeogenesis initiation during starvation?

Degradation of proteins to supply substrates for glucose production. Signup and view all the answers

What process is primarily employed to convert the energy from fatty acids to ATP during oxidation?

β-oxidation followed by the citric acid cycle and electron transport chain. Signup and view all the answers

Which statement reflects the energy cost of converting fatty acids into acyl-CoA?

It yields 2 ADP and consumes 2 ATP equivalents. Signup and view all the answers

What is the immediate metabolic fate of glycerol after its release from triacylglycerol?

It is taken up by the liver and enters glycolysis or gluconeogenesis. Signup and view all the answers

What is a critical role of CoA in the metabolism of fatty acids?

It traps fatty acids in the cell after their uptake. Signup and view all the answers

During the activation of fatty acids, what is the net ATP equivalent used in the conversion of fatty acids to acyl-CoA?

2 ATP equivalents Signup and view all the answers

What is the function of carnitine acyltransferase I (CAT I) in fatty acid metabolism?

It exchanges CoA with carnitine to allow fatty acids to enter the mitochondrial matrix. Signup and view all the answers

Which carbon of the fatty acid is oxidized first during β-oxidation?

Beta carbon Signup and view all the answers

What occurs in the mitochondria after acyl-carnitine is transported into the matrix?

Fatty acids are reattached to CoA. Signup and view all the answers

Which of the following statements correctly describes a step in the β-oxidation process?

Fatty acids are oxidized to produce acetyl-CoA through multiple cycles. Signup and view all the answers

What type of metabolic pathway does glycerol enter after being phosphorylated and oxidized?

Glycolysis or gluconeogenesis Signup and view all the answers

What is the main reason fatty acids require carnitine for transport into the mitochondria?

There is no transporter for acyl-CoA available in the mitochondrial membrane. Signup and view all the answers

Which condition is associated with excessive fat accumulation and cognitive issues, as mentioned in the content?

Fatty liver disease Signup and view all the answers

Study Notes

Chapter 27: Fatty Acid Degradation

Fatty acids are linked to glycerol in triacylglycerols (TAGs).
TAGs are the most efficient fuel source, storing high energy with little water.
TAGs are stored throughout the body, including subcutaneous (below skin) and visceral (around organs) adipose tissue.
There is also intramuscular TAG.

Using Fat as Fuel

Three stages to release energy from stored adipose tissue:
- Degradation of TAGs to release fatty acids and glycerol into the blood.
- Fatty acid activation and transport into mitochondria for oxidation.
- Fatty acid degradation to acetyl CoA for processing in the citric acid cycle.

Stage 1: "Release the Fatty Acids"

Signals like epinephrine or glucagon trigger lipid breakdown (lipolysis).
Protein kinase A activates perilipin.
Perilipin organization allows access to TAGs.
Hormone-sensitive lipase is phosphorylated to release fatty acids and glycerol.
Monoacylglycerol lipase releases the third fatty acid.
This process needs magnesium as a substrate.

Clinical Insight: Chanarin-Dorfman Syndrome

Phosphorylation of perilipin activates triglyceride lipase (ATGL).
A coactivator is crucial in this process.
In Chanarin-Dorfman syndrome, the coactivator is faulty, leading to impaired lipid breakdown.
This results in fat accumulation, dry skin, enlarged liver/muscle, and mild cognitive disability.

Results of Fatty Acid/Glycerol Release

Released glycerol is soluble in plasma and goes to the liver.
Glycerol can then enter glycolysis or gluconeogenesis.
Fatty acid is transported in the blood by albumin to target tissues.
Tissues use fatty acids for energy and then convert them to acetyl-CoA.

Glycerol Backbone is Gluconeogenic

Glycerol (3 carbons) is phosphorylated and turned into dihydroxyacetone phosphate (DHAP).
DHAP is part of glycolysis/gluconeogenesis.

Stage 2A - "Activate the Fatty Acids"

Fatty acids enter cells via "flip-flop" or a transport protein.
CoA is added to fatty acids inside the cell—this traps the fatty acid.
A 2-step reaction occurs, forming an acyl adenylate intermediate and then swapping for CoA.
This process uses ATP, converting it to AMP and PPi.

Stage 2B - "Get the Fatty Acid into The Matrix"

To be oxidized, fatty acids need to be in the mitochondrial matrix.
Acyl-CoA can't directly enter the matrix; it requires carnitine.
Carnitine acyltransferase I (CAT I) catalyzes the exchange of CoA for carnitine.
A translocase moves the acyl-carnitine into the matrix.
Carnitine acyltransferase II (CAT II) swaps carnitine back for CoA.

Stage 3 (4 Steps) - "Degrade the Fatty Acids"

This stage is known as beta-oxidation.
Four repeated reactions occur:
Oxidation of the β-carbon
Hydration of trans-Δ2-enoyl CoA
Oxidation of L-3-hydroxyacyl CoA
Cleavage of the 3-ketoacyl CoA

The 4 Steps of Degradation

Acyl-CoA dehydrogenase oxidizes the fatty acid.
Enoyl-CoA hydratase adds water.
L-3-hydroxyacyl-CoA dehydrogenase oxidizes again.
β-ketothiolase cleaves off acetyl-CoA.

The 4 Steps Repeat Depending on Length of Fatty Acid

Each cycle shortens the fatty acid by two carbons.
Each round produces 1 FADH2 and 1 NADH, plus acetyl-CoA.

Note the Final Round of β-oxidation

For a 4-carbon fatty acid (butyryl-CoA).
The final round of reactions yields 2 acetyl-CoA, 1 FADH2, and 1 NADH.

Energy Yield from Fatty Acid Oxidation

Palmitic acid (16:0) oxidation yields 106 ATP equivalents.
- 2 ATP are used for activation initially.
- The cycle produces 7 FADH2 (10.5 ATP) and 7 NADH (17.5 ATP).
- 8 acetyl-CoA units enter the TCA cycle (80 ATP).

Oxidation of Unsaturated Fat

Unsaturated fatty acids have double bonds.
Double bonds might not be in correct location—isomerases rearrange the molecules.
Oxidizing enzymes, like reductases, reposition the double bonds to facilitate beta-oxidation.

Fuel Reserves

Table shows energy reserves in a 70-kg human.
Adipose tissue holds significantly more energy than other stores.

Adapting to Starvation

Initially, glucose fuels the brain.
During extended starvation, reliance switches to fatty acids.
In later stages, ketone bodies (produced from fatty acids in the liver) become a significant energy source for the brain.
This transition conserves protein breakdown.

Ketone Bodies

Formed from acetyl-CoA in the liver (important in starvation or diabetes).
Include acetoacetate, β-hydroxybutyrate, and acetone.
Ketones are more soluble in water compared to fatty acids.
Enzymes involved in the formation of ketone bodies:
3ketothiolase
HMG Co-A synthetase
HMG-CoA cleavage enzyme
β-hydroxybutyrate dehydrogenase.
Acetoacetate spontaneously converts to acetone.

Ketone Production Also Supports Fatty Acid Oxidation

Excess acetyl-CoA from fatty acid oxidation can stimulate ketone body production, releasing CoA for further fatty acid oxidation.
Reoxidation of NADH back to NAD+ is important for continued oxidation.

Ketone Use for Energy

Ketone bodies are taken up by tissues where they are converted into acetyl-CoA.
Acetyl-CoA enters the TCA cycle for energy production.

Clinical Insight: Ketogenic Diets

Ketogenic diets, rich in fat and low in carbs, produce significant amounts of ketone bodies.
These diets are sometimes therapeutically used to treat drug-resistant epilepsy in children, potentially by altering gut bacteria and their effects on neurotransmitters.

Diabetic Ketosis

Rapid increase in ketones in diabetes (without insulin).
Adipose tissue releases excess fatty acids, overwhelming the TCA cycle, and channeling excess acetyl-CoA towards producing ketone bodies.
Acidosis results, which negatively affects tissue function.

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Description

Explore the intricate processes involved in fatty acid degradation and energy release from triacylglycerols. This chapter covers the storage of TAGs, the mechanisms of lipolysis, and the steps leading to the production of acetyl CoA. Understand how hormones trigger these metabolic pathways and their significance in energy metabolism.