Fatty Acid Metabolism Overview
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Questions and Answers

Which molecule is primarily utilized for lipogenesis in most mammals?

  • Palmitate
  • Acetate
  • Glucose (correct)
  • Fatty Acids

What is the end product of fatty acid synthesis?

  • Acetyl-CoA
  • Free Palmitate (correct)
  • Long-chain Hydrocarbons
  • NADPH

Which factor primarily regulates the rate of lipogenesis?

  • Hormone levels
  • Age of the organism
  • Nutritional state (correct)
  • Physical activity levels

Where does fatty acid synthesis occur in the cell?

<p>Cytosol (D)</p> Signup and view all the answers

What type of chemical process is lipogenesis considered?

<p>Anabolic (D)</p> Signup and view all the answers

Which of the following is a substrate for fatty acid synthesis?

<p>Lactate (B), Pyruvate (D)</p> Signup and view all the answers

Which cofactors are required for the synthesis of fatty acids?

<p>NADPH and biotin (D)</p> Signup and view all the answers

What must happen to acetyl-CoA before it can be used in fatty acid synthesis?

<p>It must be transported out of the mitochondria. (C)</p> Signup and view all the answers

What is the primary function of acetyl-CoA carboxylase in fatty acid synthesis?

<p>To synthesize malonyl-CoA (B)</p> Signup and view all the answers

Which of the following components is essential for the activity of acetyl-CoA carboxylase?

<p>Biotin (A)</p> Signup and view all the answers

How is acetyl-CoA carboxylase regulated by the metabolite citrate?

<p>Stimulates fatty acid synthesis (D)</p> Signup and view all the answers

What effect does palmitoyl-CoA have on acetyl-CoA carboxylase activity?

<p>It causes feedback inhibition (B)</p> Signup and view all the answers

What is the source of CO2 that is utilized in the reaction catalyzed by acetyl-CoA carboxylase?

<p>Bicarbonate (D)</p> Signup and view all the answers

What happens to acetyl-CoA when it needs to be transferred from the mitochondria to the cytosol?

<p>It is converted to citrate. (B)</p> Signup and view all the answers

What happens to acetyl-CoA levels when energy is required, such as during fasting?

<p>They decrease to stimulate synthesis (C)</p> Signup and view all the answers

Which enzyme catalyzes the conversion of acetyl-CoA and oxaloacetate to citrate?

<p>Citrate synthase (B)</p> Signup and view all the answers

Which hormone inhibits acetyl-CoA carboxylase activity during energy deficit states?

<p>Glucagon (B)</p> Signup and view all the answers

After citrate is cleaved in the cytosol, what are the two products formed?

<p>Acetyl-CoA and malate (D)</p> Signup and view all the answers

What are the subunits of acetyl-CoA carboxylase primarily composed of?

<p>A single polypeptide chain (B)</p> Signup and view all the answers

What is the fate of oxaloacetate in the cytosol once it is regenerated?

<p>It is transported back to the mitochondria. (A)</p> Signup and view all the answers

Which compound is required as a source of CO2 in the initial step of fatty acid synthesis?

<p>Bicarbonate (A)</p> Signup and view all the answers

Which reaction is catalyzed by malate dehydrogenase in the cytosol?

<p>Reduction of oxaloacetate to malate (B)</p> Signup and view all the answers

What is the role of malate after its formation in the cytosol?

<p>It can be converted to NADPH or pyruvate. (A)</p> Signup and view all the answers

What initial step controls fatty acid synthesis?

<p>Production of malonyl-CoA (C)</p> Signup and view all the answers

What is the main function of acetyl CoA carboxylase in fatty acid synthesis?

<p>To regulate the formation of malonyl-CoA (D)</p> Signup and view all the answers

Which step in the fatty acid synthesis cycle follows the condensation of the growing chain with activated acetate?

<p>Reduction of carbonyl to hydroxyl (C)</p> Signup and view all the answers

What is released during the condensation of acetyl-ACP and malonyl-ACP?

<p>Free ACP and CO2 (B)</p> Signup and view all the answers

What is the role of NADPH in the synthesis of fatty acids?

<p>It acts as a reducing agent (D)</p> Signup and view all the answers

What molecule is produced at the end of the first round of fatty acid elongation?

<p>Butyryl-ACP (A)</p> Signup and view all the answers

What occurs when palmitoyl-ACP is formed in the fatty acid synthesis process?

<p>It is hydrolyzed by a thio-esterase (B)</p> Signup and view all the answers

Which enzyme catalyzes the reduction of acetoacetyl-ACP to D-3-hydroxybutyryl-ACP?

<p>Beta-ketoacyl-ACP reductase (C)</p> Signup and view all the answers

During fatty acid synthesis, what is the initial attachment of the growing chain to the enzyme based on?

<p>A thioester linkage (D)</p> Signup and view all the answers

How many ATP molecules are consumed for each round of fatty acid elongation?

<p>1 (B)</p> Signup and view all the answers

What is the primary function of malonyl-CoA in fatty acid synthesis?

<p>As a two-carbon donor (A)</p> Signup and view all the answers

Which enzyme is responsible for the condensation reaction in fatty acid synthesis?

<p>β-ketoacyl-ACP synthase (C)</p> Signup and view all the answers

What is the product of 7 malonyl-CoA and 7 acetyl-CoA during fatty acid biosynthesis?

<p>Palmitate (D)</p> Signup and view all the answers

Which of the following is NOT a component of the enzyme complex responsible for introducing double bonds in fatty acids?

<p>Fatty acid synthase (A)</p> Signup and view all the answers

In which organelle does the elongation of fatty acids take place in eukaryotes?

<p>Smooth endoplasmic reticulum (C)</p> Signup and view all the answers

What is the maximum carbon position at which mammals can insert double bonds in a fatty acid chain?

<p>C-9 (B)</p> Signup and view all the answers

Which molecule is reduced during the seven cycles of fatty acid synthesis?

<p>β-keto group (C)</p> Signup and view all the answers

Flashcards

Fatty Acid Catabolism

The process of breaking down fatty acids into smaller units, primarily for energy production.

Fatty Acid Biosynthesis (Lipogenesis)

The process of constructing fatty acids from smaller units.

Acetyl-CoA

The main substrate for lipogenesis, meaning it's the starting material for building fatty acids.

Palmitate

The end product of fatty acid biosynthesis, a saturated fatty acid with 16 carbon atoms.

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Cytosol

The primary location where fatty acid synthesis takes place within cells.

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Lipogenesis

The process of storing excess carbohydrates as fat for later use.

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ATP

A molecule that carries energy and is essential for many metabolic processes.

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Nutritional State

A key regulator for lipogenesis, meaning it controls how fast fatty acids are made.

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Fatty acid synthase (FAS)

An enzyme involved in fatty acid synthesis that catalyzes the addition of two-carbon units from malonyl-CoA to a growing fatty acyl chain.

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FAS cycle

A four-step process that elongates a fatty acyl chain by two carbons using NADPH as the electron donor and two enzyme-bound -SH groups.

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Allosteric regulation of acetyl CoA carboxylase

Citrate, a citric acid cycle intermediate, allosterically activates acetyl CoA carboxylase.

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Acyl carrier protein (ACP)

The molecule that carries the growing fatty acyl chain during fatty acid synthesis.

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Condensation

The first step in FAS cycle, where acetyl-ACP and malonyl-ACP condense to form acetoacetyl-ACP, releasing free ACP and CO2.

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Reduction

The second step in FAS cycle, where acetoacetyl-ACP is reduced to D-3-hydroxybutyryl-ACP using NADPH.

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Dehydration

The third step in FAS cycle, where D-3-hydroxybutyryl-ACP is dehydrated to produce crotonyl-ACP.

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Reduction (second step)

The fourth step in FAS cycle, where crotonyl-ACP is reduced by NADPH to give butyryl-ACP.

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Acetyl-CoA Shuttle: Citrate as Transporter

Acetyl-CoA, produced in the mitochondria, is transported to the cytosol for lipid synthesis. However, the inner mitochondrial membrane is impermeable to acetyl-CoA. To solve this problem, acetyl-CoA is converted into citrate, which can easily pass through the membrane.

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Re-generating Acetyl-CoA in the Cytosol

Citrate, once inside the cytosol, is cleaved back into acetyl-CoA and oxaloacetate by the enzyme citrate lyase.

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Oxaloacetate Conversion to Malate

Oxaloacetate, a product of citrate cleavage, cannot directly cross the mitochondrial membrane. It is converted into malate by the enzyme malate dehydrogenase.

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Malate-α-Ketoglutarate Transporter

Malate can be reoxidized back to oxaloacetate, providing a way to shuttle oxaloacetate back into the mitochondria.

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Malate's Role in NADPH Production

Malate can be converted into NADPH and pyruvate by the enzyme malic enzyme. NADPH is essential for lipid synthesis.

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Formation of Malonyl-CoA: the Initial Step

The enzyme acetyl-CoA carboxylase catalyzes the reaction of acetyl-CoA with bicarbonate and ATP to produce malonyl-CoA, the first committed step in fatty acid synthesis.

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Bicarbonate as CO2 Source

Bicarbonate provides the source of CO2 in the carboxylation of acetyl-CoA to malonyl-CoA.

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Acetyl-CoA Carboxylase

Acetyl-CoA carboxylase is the enzyme responsible for the carboxylation of acetyl-CoA to malonyl-CoA, a critical step in fatty acid synthesis.

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Acetyl-CoA carboxylase (ACC)

An enzyme crucial for fatty acid synthesis, it catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA. It requires biotin as a cofactor and is composed of three subunits, each with specific roles.

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Malonyl-CoA

A key intermediate in fatty acid synthesis produced by acetyl-CoA carboxylase. It provides the two-carbon units for building fatty acid chains.

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Production of Malonyl-CoA

The initial and controlling step in fatty acid synthesis. It represents the commitment of acetyl-CoA to fatty acid biosynthesis.

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Citrate activation of ACC

The allosteric activation of acetyl-CoA carboxylase (ACC) by citrate signals excess energy and triggers the conversion of carbohydrates to fat.

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Palmitoyl-CoA inhibition of ACC

A feedback-mediated inhibition of acetyl-CoA carboxylase by palmitoyl-CoA. It serves to regulate fat synthesis, ensuring that energy is not wasted.

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Hormonal regulation of ACC

The process of inhibiting acetyl-CoA carboxylase (ACC) by hormones like glucagon and epinephrine, which results in a decrease in fatty acid synthesis. This strategy helps regulate energy stores during times of energy deprivation.

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Regulation of acetyl-CoA carboxylase

The process of regulating acetyl-CoA carboxylase activity by both allosteric effectors and hormonal signals. This ensures that the synthesis of fatty acids is responsive to the body's energy needs and nutritional status.

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Fatty Acid Biosynthesis

The process of synthesizing fatty acids from smaller molecules, primarily using acetyl-CoA and malonyl-CoA as building blocks.

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Fatty Acid Synthase

This enzyme complex catalyzes all the reactions of fatty acid elongation in eukaryotes, facilitating efficient chain lengthening.

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Condensation Reaction in Fatty Acid Synthesis

The first reaction in fatty acid biosynthesis is the condensation of acetyl-CoA and malonyl-CoA, facilitated by the enzyme β-ketoacyl-ACP synthase (KS).

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Fatty Acid Desaturation

The process of adding double bonds to fatty acyl-CoA, occurring in the smooth endoplasmic reticulum of eukaryotes.

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Desaturase

This enzyme catalyzes the desaturation reaction, introducing double bonds into fatty acids and requiring molecular oxygen.

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Limitations of Mammalian Desaturation

Mammals have a limited ability to desaturate fatty acids beyond carbon 9, meaning they cannot synthesize certain essential fatty acids.

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Dehydration Reaction

The process of removing water molecules from a compound, often occurring during fatty acid synthesis.

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Study Notes

Fatty Acid Metabolism

  • Fatty acid metabolism involves the breakdown and synthesis of fatty acids.
  • Breakdown of fatty acids, also known as fatty acid catabolism, occurs when there is a scarcity of carbohydrates and energy.
  • Synthesis of fatty acids, often called fatty acid biosynthesis, occurs when carbohydrates and energy are abundant.

Fatty Acid Breakdown (Catabolism)

  • Fatty acid catabolism primarily takes place in mitochondria.
  • It begins with the activation of fatty acids.
  • The activated fatty acids undergo a cycle of beta-oxidation reactions, creating acetyl-CoA and reducing equivalents (NADH and FADH2).

Fatty Acid Synthesis (Anabolism)

  • Fatty acid synthesis occurs in the cytosol.
  • Acetyl-CoA is the initial substrate, and it shuttles into the cytosol from the mitochondria as citrate.
  • Synthesis involves a series of reactions, using malonyl-CoA as a building block, to lengthen the fatty acid chain
  • Involves reduction steps and utilizes NADPH as reducing agents.

Regulation of Fatty Acid Synthesis

  • The main regulatory enzyme in fatty acid synthesis is acetyl-CoA carboxylase (ACC).
  • ACC is allosterically regulated; citrate activates it, while palmitoyl-CoA inhibits it.
  • Hormonal regulation also plays a key role: glucagon and epinephrine inhibit ACC, while insulin promotes it.
  • Hormonal changes directly affect the activity of ACC to regulate the biosynthesis process.

Fatty Acid Synthase (FAS)

  • FAS is a multifunctional enzyme.
  • FAS catalyzes a repeating four-step sequence to elongate the fatty acid chain; it uses NADPH as the electron donor and two enzyme-bound -SH groups for activation.
  • The first round of elongation produces butyryl-ACP; subsequently, the cycle repeats adding two carbons to the chain.
  • This cycle continues until a 16-carbon palmitoyl-ACP is formed.

Key Molecules and Cofactors

  • Acetyl-CoA, malonyl-CoA, citrate and fatty acid synthase are key players in fatty acid metabolism.
  • Biotin, NADPH, and ATP are needed as cofactors in various steps.
  • Some other cofactors needed for fatty acid synthesis are NADPH, ATP, Mn2+, biotin, and HCO3-.

Stoichiometry

  • Synthesis of palmitate (16:0) involves specific steps requiring ATP and NADPH.
  • The overall stoichiometry for palmitate synthesis is represented by a specific equation.

Formation of Double Bonds

  • In eukaryotes, the smooth endoplasmic reticulum (SER) has enzymes that introduce double bonds into fatty acyl CoA molecules.
  • This process utilizes molecular oxygen and a complex of three enzymes: NADH-cytochrome b5 reductase, cytochrome b5, and desaturase.
  • Mammals lack the enzymes to introduce double bonds beyond carbon 9; hence, linoleate and linolenate are considered essential fatty acids.

Summary of differences between fatty acid catabolism and anabolism

  • Catabolism occurs in the mitochondria and produces energy, while anabolism occurs in the cytosol and needs significant energy.
  • Catabolism is exergonic (releases energy) and oxidative (oxidizes fatty acids); anabolism is endergonic (requires energy) and reductive (reduces fatty acids).
  • Different coenzymes, electron carriers and locations in the cell are involved.

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Fatty Acid Metabolism Part II PDF

Description

Explore the intricacies of fatty acid metabolism, including both catabolism and anabolism. This quiz covers key processes such as fatty acid breakdown in mitochondria and synthesis in the cytosol. Test your understanding of the activation, beta-oxidation, and the role of Acetyl-CoA and NADPH.

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