17.2 Oxidation of Fatty Acids

1. Mitochondrial oxidation of fatty acids stages

B-oxidation -Fatty acid oxidation breaks down fatty acids by removing 2-carbon units as acetyl-CoA from the carboxyl end in each step. For example, the 16-carbon palmitate requires 7 rounds to fully break down, producing 8 acetyl-CoA molecules. In each round, 2 carbons are removed, and by the end, the entire chain is converted into acetyl-CoA units. Additionally, each step removes 4 hydrogen atoms (2 pairs of electrons) with the help of dehydrogenase enzymes. This stepwise breakdown provides energy for the cell.

1. Think of it like cutting a 16-link chain into 8 smaller 2-link segments!

2. Mitochondrial oxidation of fatty acids stages

In the second stage of fatty acid oxidation, the acetyl groups from acetyl-CoA are oxidized in the citric acid cycle within the mitochondria. This process connects with acetyl-CoA from glucose that comes from glycolysis and pyruvate oxidation. During the first two stages of fatty acid oxidation, NADH and FADH₂ are produced as reduced electron carriers.

3. Mitochondrial oxidation of fatty acids stages

I NADH and FADH₂ donate electrons to the mitochondrial respiratory chain. These electrons move to oxygen, which helps convert ADP into ATP. As a result, the energy from fatty acid oxidation is stored as ATP.

TFP - Trifunctional protein

a heterooctamer of 4 beta and 4 alpha subunits 

• Alpha subunit (2 activities): the enoyl-CoA hydratase & the β-hydroxyacyl-CoA dehydrogenase 

• β subunits: thiolase activity 

Another term for acyl-CoA acetyltransferase

thiolase

How can Acetyl-CoA be oxidized

Co2 and H2O by citric acid cycle

Oxidation of Unsaturated Fatty Acids Requires Two Additional Reactions

Unsaturated fatty acids: one or more double bonds in cis configuration in Carbon chain that cannot be acted upon by enoyl-CoA hydratases use two enzymes instead

• isomerase - delta 3, delta 2 enoyl CoA isomerase

• reductase - 2,4 dienoyl-CoA reductase

Fatty Acids with odd number of carbons are common in what?

Plants and marrine organisims

Propionate is found in large amounts what organisims?

Cattle and other ruminant during fermination in the rumen, where propinate is absorebd in blood and oxidized in liver + tissues

In odd fatty acid oxidation what is changed in the last step what is changed?

a fatty acyl–CoA with a five-carbon fatty acid, then is oxidized and cleaved, producing acetyl- CoA and propionyl-CoA

During odd number fatty acid oxidation where does acetyl-CoA enter?

Citric Acid Cycle

uring odd number fatty acid oxidation where does propionyl-CoA enter?

three enzymes

1. Propionyl- CoA carboxylase

2. methylmanoyl-CoA epimerase

3. methylmayol- CoA mutase

How is fatty acid oxidation regulated?

Fatty acid oxidation is tightly regulated and occurs only when energy is needed

What options are available for fatty acyl-CoA in the liver

In the liver, fatty acyl-CoA can either be oxidized in the mitochondria or converted into fats and phospholipids in the cytosol

What determines the pathway taken by fatty acyl-CoA?

depends on how quickly long-chain fatty acyl-CoA is transported into the mitochondria

What is the role of the carnitine shuttle?

The carnitine shuttle carries fatty acyl groups into the mitochondria as fatty acyl-carnitine and serves as a key regulatory step for fatty acid oxidation.

What types of regulation affect the activity of enzymes involved in fatty acid oxidation?

Fatty acid oxidation is regulated through short-term mechanisms that modulate existing enzyme activity and transcriptional regulation that changes the number of enzyme molecules over a longer time scale (minutes to hours).

What are PPARs, and what is their role?

PPARs ( peroxisome proliferator-activated receptor) are a family of nuclear receptors that act as transcription factors, affecting various metabolic processes in response to fatty acid-like ligands. They help regulate genes essential for fatty acid oxidation.

Which tissues do PPARs act upon?

PPARs act in muscle, adipose tissue, and liver.

When are genes for fatty acid oxidation activated?

Genes for fatty acid oxidation are activated when there is an increased demand for energy from fat catabolism, such as during fasting or longer-term starvation.

How does glucagon influence lipid catabolism?

Glucagon, released in response to low blood glucose, can activate certain genes for lipid catabolism through cAMP and the transcription factor CREB.

What are the principal fuels for heart muscle in the fetus?

n the fetus, the principal fuels for heart muscle are glucose and lactate.

What fuel becomes the main source for the neonatal heart after birth?

After birth, fatty acids become the main fuel for the neonatal heart.

What happens during the transition from fetal to neonatal metabolism in the heart?

During this transition, specific genes essential for fatty acid metabolism are activated.

Which transcription factors are involved in regulating enzyme expression for fatty acid metabolism?

Transcription factors from the PPAR family play crucial roles in regulating enzyme expression for fatty acid metabolism.

Where does fatty acid oxidation primarily occur in the body?

skeletal and heart muscle

How does endurance training affect fatty acid oxidation in muscles?

Endurance training increases the expression of fatty acid–oxidizing enzymes in muscle, enhancing the oxidative capacity of the muscle.

What is one of the most severe disorders related to fatty acid oxidation?

A severe disorder results from the loss of long-chain 3-hydroxyacyl-CoA dehydrogenase activity in the trifunctional protein (TFP).

What are the consequences of defects in the alpha or beta subunits of TFP?

Defects in these subunits affect all three activities of TFP, leading to serious heart disease and abnormal skeletal muscle.

Where is the major site of fatty acid oxidation in animal cells?

the mitochondrial matrix.

Where is the major site of fatty acid oxidation in plant cells?

in peroxisomes

What are the intermediates for oxidation of fatty acids in peroxisomes?

coenzyme A derivatives

What are the four steps involved in fatty acid oxidation in peroxisomes?

1. Dehydrogenation

2. Addition of water to the double bond

3. Oxidation of β-hydroxyacyl-CoA to a ketone

4. Thiolytic cleavage by coenzyme A

Where do identical reactions to those in peroxisomes also occur?

In glyoxysomes, which are found only in germinating seeds.

What is one key difference between peroxisomal and mitochondrial fatty acid oxidation?

A key difference is in the chemistry of the first step of oxidation

What enzyme is involved in the first step of fatty acid oxidation in peroxisomes?

acyl-CoA oxidase

What does acyl-CoA oxidase produce during the oxidation process in peroxisomes?

It produces hydrogen peroxide (H₂O₂), hence the name “peroxisomes

How is hydrogen peroxide handled in peroxisomes?

Hydrogen peroxide is immediately cleaved to water (H₂O) and oxygen (O₂) by catalase.

How does electron transfer differ in mitochondria compared to peroxisomes?

in mitochondria, electrons from the first oxidation step pass through the respiratory chain to produce ATP, while in peroxisomes, the energy is not conserved as ATP but is lost as heat

What is the second key difference between peroxisomal and mitochondrial fatty acid oxidation?

The peroxisomal system is more active on very-long-chain fatty acids and branched-chain fatty acids

The peroxisomal system is more active on very-long-chain fatty acids and branched-chain fatty acids?

Very-long-chain fatty acids like hexacosanoic acid (26:0) and branched-chain fatty acids like phytanic acid and pristanic aci

Where do these less-common fatty acids come from?

They are obtained from dietary intake of dairy products, ruminant animal fat, meat, and fish

What unique pathway do germinating seeds of plants use with acetyl-CoA?

the glyoxylate cycle

What is phytanic acid?

a long-chain fatty acid with methyl branches, derived from the phytol side chain of chlorophyll

Why is the oxidation of phytanic acid impossible?

presence of a methyl group on the carbon of phytanic acid prevents the formation of a β-keto intermediate, making oxidation impossible

How do humans obtain phytanic acid?

Humans obtain phytanic acid primarily from dietary sources, such as dairy products and the fats of ruminant animals

How is phytanic acid produced in ruminant animals?

Microorganisms in the rumen of ruminant animals produce phytanic acid as they digest plant chlorophyll

What is the typical daily intake of phytanic acid in a Western diet?

50 to 100 mg of phytanic acid per day

What happens when adenylyl cyclase is stimulated in adipocytes

iincreases of the production of **cyclic AMP (cAMP)**, which acts as a second messenger inside the c

TFP subunits - a4B4

a subunit contains - enoyl COA and B - hydroxyacyl COA dehydrogenasw

B subunit contains - thiolase activity

During fatty acid oxidation FADH2 produce what in respiratory chain?

1.5 molecules of ATP

During fatty acid oxidation NADH2 produces what in mictochondrial dehydrogenase?

2.5 ATP molecules

How much molecules are formed from ATP of FADH2 AND NADH2?

4

What is water called that passes through O2 in fatty acid oxidation?

metabolic water

Auxillary enzymes in unsaturated fatty acid

isomerase and reductase - change unsaturated enzymes to substrates for b oxidation

oleate

monounsaturated fatty acid = isomerase