Fatty Acid Oxidation Processes

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Questions and Answers

What is the primary function of carnitine in fatty acid metabolism?

Activates long-chain fatty acids for oxidation.

Acts as a coenzyme in β-oxidation.

Synthesizes fatty acids from acetyl-CoA.

Facilitates the transport of long-chain fatty acids into the mitochondria. (correct)

Which coenzymes are utilized during fatty acid oxidation?

NADP and CoA

CoQ and NADH

FAD and ATP

NAD and FAD (correct)

What does the β-oxidation pathway primarily produce from fatty acids?

Palmitate

Propionyl-CoA

Glycerol

Acetyl-CoA (correct)

Which statement about fatty acid oxidation is NOT correct?

Fatty acid synthesis occurs in the mitochondrial matrix. Signup and view all the answers

Which enzyme catalyzes the first step in the activation of fatty acids?

Acyl-CoA synthetase Signup and view all the answers

What is the product formed when palmitoyl-CoA undergoes complete β-oxidation?

8 acetyl-CoA Signup and view all the answers

Which organ is responsible for synthesizing carnitine from amino acids?

Liver Signup and view all the answers

What type of process is fatty acid oxidation considered to be?

Aerobic process Signup and view all the answers

What is the final product of the oxidation of odd-chain fatty acids after propionyl-CoA is formed?

Succinyl-CoA Signup and view all the answers

Which feature differentiates peroxisomal β-oxidation from mitochondrial β-oxidation?

Production of H2O2 Signup and view all the answers

What is the primary metabolic role of propionyl-CoA derived from odd-chain fatty acid oxidation?

TCA cycle substrate Signup and view all the answers

For which type of fatty acid is α-oxidation primarily utilized?

Branched-chain fatty acids Signup and view all the answers

What is produced during the oxidation of unsaturated fatty acids that reduces energy efficiency compared to saturated fatty acids?

Less ATP Signup and view all the answers

Which enzymatic action converts the 3-cis derivative of monounsaturated fatty acids during β-oxidation?

2,3-enoylCoA isomerase Signup and view all the answers

In peroxisomal β-oxidation, how is the FADH2 produced oxidized?

By molecular oxygen Signup and view all the answers

ω-oxidation of fatty acids converts which functional group into a dicarboxylic acid?

Methyl group Signup and view all the answers

What is a common sign of carnitine deficiency?

Episodic periods of hypoglycemia with muscular weakness Signup and view all the answers

Which condition is primarily caused by a deficiency of mitochondrial medium chain acyl-CoA dehydrogenase?

Dicarboxylic aciduria Signup and view all the answers

What is the main treatment for carnitine deficiency?

Oral supplementation of carnitine Signup and view all the answers

Which of the following is a symptom of Refsum disease?

Neurological symptoms due to accumulation of phytanic acid Signup and view all the answers

What is the underlying issue in Zellweger's syndrome?

Inherited absence of peroxisomes in all tissues Signup and view all the answers

Study Notes

Oxidation of Fatty Acids

Fatty acids (FAs) are oxidized to acetyl-CoA and synthesized from acetyl-CoA.
FA oxidation is a different process than FA biosynthesis, occurring in a separate cellular compartment.
FA oxidation occurs in the mitochondria.
FA oxidation is an aerobic process, requiring oxygen.
NAD and FAD are used as coenzymes, generating ATP.
FAs are transported in the blood as free FAs.
Longer-chain FAs combine with albumin and are attached to a FA binding protein in cells.

Steps of FA Oxidation

Activation: This is the only step in FA degradation requiring energy from ATP.
- FA + ATP + CoA → Acyl-CoA + AMP + PPi.
- Several acyl-CoA synthases are specific to different chain lengths.
Transport of long-chain FAs into mitochondria
- Activation of short-chain fatty acids and their oxidation in mitochondria can occur independently of carnitine.
- Long-chain acyl-CoAs cannot penetrate the inner mitochondrial membrane and become oxidized unless they first form acylcarnitine.
- Long-chain FAs penetrate the inner mitochondrial membrane as carnitine derivatives.
- Carnitine (β-hydroxy y-trimethyl ammonium butyrate) is abundant in muscle.

β-oxidation of Fatty Acids

In β-oxidation, two carbons are activated at a time from acyl-CoA molecules starting at the carboxyl end.
The chain is broken between α(2) and β(3) carbon atoms.
The two-carbon units formed are acetyl-CoA.
For example, palmitoyl-CoA forms 8 acetyl-CoA molecules.
Several enzymes, collectively called FA oxidase, catalyze the reaction in the mitochondrial matrix or inner membrane adjacent to the respiratory chain.
This system is coupled with ADP phosphorylation to ATP.

β-Oxidation in Peroxisomes

Very long-chain FAs (20 carbons or longer) undergo preliminary β-oxidation in peroxisomes, leading to acetyl-CoA and H₂O₂ formation.
The initial dehydrogenation in peroxisomes is catalyzed by an FAD-containing acyl-CoA oxidase.
The FADH₂ produced is oxidized by molecular oxygen, which is reduced to H₂O₂.
H₂O₂ is reduced to H₂O by catalase.
Peroxisomal β-oxidation helps shorten the side chain of cholesterol in bile acid formation.

α-Oxidation of FAs

Removal of one carbon at a time from the carboxyl end of the fatty acid molecule (in brain tissue).
Branched-chain FAs (like phytanic acid) are not substrates for acyl-CoA dehydrogenase, due to a methyl group on the β-carbon.
Instead, they are hydroxylated at the α-carbon by an α-hydroxylase, then decarboxylated, and activated to their CoA derivative.
This derivative is then a substrate for the enzymes of β-oxidation.
α-oxidation doesn't produce high-energy phosphate.

ω-Oxidation of FAs

A minor pathway involving hydroxylase enzymes and cytochrome P450 in the endoplasmic reticulum (ER).
The -CH₃ group is converted to -CH₂OH, and subsequently oxidized to -COOH, forming a dicarboxylic acid.

Oxidation of Unsaturated FAs

Oxidation of unsaturated FAs produces less energy than that of saturated FAs because they are less reduced.
Fewer reducing equivalents are produced.

Oxidation of Monounsaturated FAs

Oxidation of monounsaturated FAs (e.g., oleic acid) requires additional enzyme 2,3-enoyl-CoA isomerase, converting the 3-cis derivative to the 2-trans derivative, used as a substrate for hydroxylase.

Oxidation of Polyunsaturated FAs

Oxidation of polyunsaturated FAs (e.g., linoleic acid) needs NADPH-dependent reductase in addition to isomerase.

Clinical Conditions

Carnitine deficiency: Characterized by episodic hypoglycemia and muscular weakness. Caused by conditions like preterm infants, liver diseases, malnutrition, vegetarians, pregnancy, severe infections, burns, trauma, hemodialysis, or organic aciduria patients.
Treatment with oral carnitine supplementation.
Inherited defects in β-oxidation enzymes: lead to nonketotic hypoglycemia, coma and fatty liver
Dicarboxylic aciduria: Characterized by the excretion of C6-C10 ω-dicarboxylic acids and nonketotic hypoglycemia. It's caused by a lack of mitochondrial medium-chain acyl-CoA dehydrogenase, which impairs β-oxidation but increases ω-oxidation, ultimately producing medium-chain dicarboxylic acids.

Additional Conditions

Refsum disease: A rare autosomal recessive disorder caused by a deficiency of α-hydroxylase, leading to phytanic acid accumulation in plasma and tissues; mainly neurologic symptoms.
Zellweger's syndrome: Inherited absence of peroxisomes in all tissues leading to accumulation of very long-chain FAs in blood and tissues.

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Description

Test your understanding of the oxidation of fatty acids, a crucial metabolic process occurring in mitochondria. This quiz covers key steps such as activation, transport, and the role of coenzymes in ATP generation. Dive into the complexities of fatty acid degradation and its importance in metabolism.