Harper's Biochemistry Chapter 23 - Biosynthesis of Fatty Acids & Eicosanoids

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Questions and Answers

What is the main product of fatty acid synthesis favored in most tissues?

Palmitate (correct)

Arachidonic acid

Linoleate

Stearate

Which enzyme is primarily responsible for the initial step in fatty acid synthesis?

Covalent desaturase

Elongation enzyme

Acetyl-CoA carboxylase (correct)

Fatty acid synthase

What is the main source of reducing equivalents for fatty acid synthesis?

NADPH (correct)

NADH

Coenzyme A

FADH2

Which of the following is NOT a nutritionally essential fatty acid?

Oleic acid Signup and view all the answers

Which pathways are responsible for the formation of various classes of eicosanoids?

Cyclooxygenase and lipoxygenase pathways Signup and view all the answers

What regulates the activity of acetyl-CoA carboxylase?

Hormonal signaling and allosteric modulation Signup and view all the answers

Which of the following correctly describes the role of NSAIDs like aspirin in relation to fatty acids?

They block the synthesis of thromboxanes and prostaglandins. Signup and view all the answers

What effect does citrate have on CoA carboxylase?

It converts the enzyme from an inactive dimer to an active polymeric form. Signup and view all the answers

What role does long-chain acyl-CoA play in the regulation of CoA carboxylase?

It inactivates the enzyme through phosphorylation and inhibits citrate transport. Signup and view all the answers

How does acyl-CoA affect the synthesis of new fatty acids?

It prevents fatty acid synthesis by inhibiting citrate transport. Signup and view all the answers

What results from the accumulation of acyl-CoA in tissues?

Decreased synthesis of new fatty acid due to enzyme inhibition. Signup and view all the answers

What is the result of acyl-CoA's inhibition of the tricarboxylate transporter?

Decreased activation of CoA carboxylase by lowering cytosolic citrate levels. Signup and view all the answers

What is the activation process required for palmitate before it can enter metabolic pathways?

Conversion to acyl-CoA Signup and view all the answers

What are the possible fates of activated acyl-CoA in the cytosol?

Esterification into acylglycerols Signup and view all the answers

Which enzyme catalyzes the conversion of malate to pyruvate that is a significant source of NADPH?

Malic enzyme Signup and view all the answers

What is the overall equation for the synthesis of palmitate from acetyl-CoA and malonyl-CoA?

CH3CO-SCoA + 7 HOOCCH2CO-SCoA + 14 NADPH + 14 H+ → CH3(CH2)14COOH + 7 CO2 + 6 H2O + 8 CoA-SH + 14 NADP+ Signup and view all the answers

What is the principal building block of fatty acids?

Acetyl-CoA Signup and view all the answers

What is the main function of acetyl-CoA in fatty acid biosynthesis?

It serves as a precursor for fatty acid elongation. Signup and view all the answers

How does acetyl-CoA transport across mitochondrial membranes to the cytosol?

Involvement of citrate Signup and view all the answers

What source of fatty acids is particularly associated with propionyl-CoA?

Long-chain fatty acids with odd carbon numbers Signup and view all the answers

Which enzyme is responsible for converting acetyl-CoA to malonyl-CoA?

Acetyl-CoA carboxylase Signup and view all the answers

Which of the following statements about mammary gland thioesterase is accurate?

It is specific for acyl residues of C8, C10, or C12. Signup and view all the answers

During the fatty acid synthesis cycle, which compound is predominantly formed after cycling through steps 2-5 seven times?

Palmitate Signup and view all the answers

What role does NADPH play in the fatty acid synthesis process?

It provides electrons for the reduction steps. Signup and view all the answers

What is one of the reactions that contributes to NADPH production in ruminants?

Extramitochondrial isocitrate dehydrogenase reaction Signup and view all the answers

Which enzyme is responsible for the dehydration step in fatty acid synthesis?

Dehydratase Signup and view all the answers

What is the significance of the multienzyme complex in fatty acid biosynthesis?

It enhances the efficiency by channeling intermediates. Signup and view all the answers

Which of the following statements about fatty acid elongation is correct?

It involves the addition of two-carbon units. Signup and view all the answers

Which substrate is ultimately used in the reduction steps during fatty acid synthesis?

NADPH Signup and view all the answers

What is the result of the action of the thioesterase enzyme in the fatty acid synthesis pathway?

It releases the newly synthesized fatty acid. Signup and view all the answers

What is the primary reason for the increase in stearyl-CoA during brain myelination?

To supply C22 and C24 fatty acids for sphingolipids Signup and view all the answers

How does the metabolism of fructose differ from glucose in terms of regulating lipogenesis?

Fructose bypasses the phosphofructokinase control point in glycolysis Signup and view all the answers

What role does lipogenesis play in the nutritional state of an organism?

It facilitates fat storage in anticipation of caloric deficiency Signup and view all the answers

What regulates long-chain fatty acid synthesis in the long term?

Changes in gene expression governing enzyme synthesis Signup and view all the answers

Which metabolic intermediates can be converted to fat through lipogenesis?

Glucose, pyruvate, lactate, and acetyl-CoA Signup and view all the answers

In response to what conditions is excess carbohydrate likely to be stored as fat?

In anticipation of periods like starvation and hibernation Signup and view all the answers

Which enzyme's regulation is implicated in the regulation of lipogenesis?

Acetyl-CoA carboxylase Signup and view all the answers

What is the main effect of feeding sucrose instead of glucose on lipogenesis?

Increased lipogenic pathway flux Signup and view all the answers

In the context of lipogenesis, what is the significance of the anabolic phase in feeding cycles?

It is where energy is stored as fat Signup and view all the answers

Which statement best describes the function of malonyl-CoA in lipogenesis?

It is an essential building block for fatty acid elongation Signup and view all the answers

What is the primary function of the fatty acid synthase multienzyme complex?

To facilitate the formation of fatty acids from multiple precursors. Signup and view all the answers

Which enzymes are primarily responsible for the synthesis of polyunsaturated fatty acids?

Desaturase and elongation enzymes. Signup and view all the answers

What effect do thromboxanes have in the body?

They mediate pain and inflammation responses. Signup and view all the answers

How does nutritional status influence fatty acid synthesis?

It affects the activity of acetyl-CoA carboxylase and other regulatory enzymes. Signup and view all the answers

What is the function of malonyl-CoA in the elongation of fatty acid chains?

It donates a C2 unit during fatty acid chain elongation. Signup and view all the answers

What is the role of malonyl-CoA in fatty acid biosynthesis?

It inhibits the transport of fatty acids into the mitochondria. Signup and view all the answers

What regulates the rate of lipogenesis in the well-fed state?

High proportion of carbohydrates in the diet. Signup and view all the answers

What is the primary reason for the need for dietary intake of certain fatty acids?

Certain fatty acids cannot be synthesized due to lack of specific enzymes. Signup and view all the answers

What is the role of NADPH in the fatty acid synthesis process?

It serves as a reducing agent during the elongation steps. Signup and view all the answers

Which statement accurately reflects the regulation of fatty acid elongation in the endoplasmic reticulum?

It is inversely related to the concentration of serum-free fatty acids. Signup and view all the answers

What is the primary product formed after the repeated condensation of two carbon units during fatty acid synthesis?

Palmitate. Signup and view all the answers

What is a primary source of acetyl-CoA in ruminants for fatty acid synthesis?

Carbohydrate digestion in the rumen. Signup and view all the answers

Which enzyme is responsible for the dehydration step in the fatty acid synthesis process?

Dehydratase Signup and view all the answers

What role does the Acyl Carrier Protein (ACP) play in the fatty acid synthesis process?

It serves as a structural component of the fatty acid synthase complex. Signup and view all the answers

How many times does the sequence of reactions repeat during the assembly of a saturated 16-carbon fatty acid like palmitate?

Six times Signup and view all the answers

What is released from the fatty acid synthase complex at the end of the synthesis of palmitate?

Palmitic acid Signup and view all the answers

Which molecule is reduced during the fatty acid synthesis process by the 3-ketoacylreductase?

3-ketoacyl group Signup and view all the answers

In which form is pantothenic acid incorporated into the ACP for fatty acid synthesis?

4′-phosphopantetheine Signup and view all the answers

What happens to the acyl residue after being transferred from the ACP during the synthesis cycle?

It is reattached to a new malonyl-CoA. Signup and view all the answers

Which enzyme catalyzes the reduction step that follows the dehydration of the acyl group in fatty acid synthesis?

Enoyl reductase Signup and view all the answers

What is the final product formed after completing the fatty acid synthesis cycle, involving multiple repetitive steps?

Hexadecanoate Signup and view all the answers

What is the role of biotin in the synthesis of malonyl-CoA?

It serves as a coenzyme for carboxylation reactions. Signup and view all the answers

Which statement accurately describes the overall reaction catalyzed by acetyl-CoA carboxylase?

It combines acetyl-CoA with bicarbonate to form malonyl-CoA. Signup and view all the answers

During which step of the overall reaction is ATP utilized?

Step 1 only Signup and view all the answers

What distinguishes the E2 enzyme in the acetyl-CoA carboxylase complex from the E1 enzyme?

E2 transfers the carboxyl group to the substrate. Signup and view all the answers

What is the primary function of malonyl-CoA in the carboxylation reaction?

It provides the carbon units needed for fatty acid synthesis. Signup and view all the answers

Which compound is produced as a byproduct during the ATP-dependent carboxylation of acetyl-CoA?

ADP Signup and view all the answers

Why is the formation of malonyl-CoA considered a critical regulatory step in fatty acid metabolism?

Malonyl-CoA restricts the transport of fatty acids into the mitochondria. Signup and view all the answers

Which of the following best describes the biochemical nature of acetyl-CoA carboxylase?

It operates as a multienzyme complex. Signup and view all the answers

What is the significance of bicarbonate in the reaction catalyzed by acetyl-CoA carboxylase?

It serves as a carbon source for the formation of malonyl-CoA. Signup and view all the answers

What must occur before palmitate can proceed through metabolic pathways?

It must be converted to fatty acyl-CoA Signup and view all the answers

Which of the following is a potential fate of acyl-CoA in the cytosol?

Synthesis of diacylglycerols Signup and view all the answers

Where does the synthesis of palmitate occur within the cell?

In the cytosol Signup and view all the answers

What is the role of citrate in the transport of acetyl-CoA?

To facilitate the entry of acetyl-CoA into the cytosol Signup and view all the answers

What initiates the synthesis of long-chain fatty acids with an odd number of carbon atoms?

Propionyl-CoA as a primer Signup and view all the answers

Which reaction is a significant source of NADPH in ruminants?

Conversion of malate to pyruvate Signup and view all the answers

What is the overall reaction for the synthesis of palmitate from its precursors?

1 Acetyl-CoA and 7 Malonyl-CoA yield 1 Palmitate and 7 CO2 Signup and view all the answers

Which acyl residue does the thioesterase in the mammary gland specifically target?

C8, C10, and C12 acyl residues Signup and view all the answers

What type of fatty acids are particularly found in ruminant fat and milk?

Odd-numbered long-chain fatty acids Signup and view all the answers

How does palmitate's carbon framework increase during its synthesis?

Through the addition of malonyl-CoA units Signup and view all the answers

Match the following steps in fatty acid synthesis with their corresponding enzymes:

Carboxylation of biotin = Biotin carboxylase Transfer of carboxyl group to acetyl-CoA = Carboxyl transferase Formation of acetoacetyl enzyme = 3-ketoacyl synthase Formation of fatty acyl-malonyl enzyme = Malonyl acetyl transacylase Signup and view all the answers

Match the following components with their roles in fatty acid synthesis:

Acetyl-CoA = Priming molecule for synthesis Biotin = Cofactor for biotin carboxylase Malonyl-CoA = Donor of 2-carbon units ATP = Energy source for carboxylation Signup and view all the answers

Match each component of the fatty acid synthase complex with its function:

ACP = Carries acyl groups during synthesis Regulatory allosteric site = Modulates enzyme activity Cysteine —SH group = Participates in acyl group transfer Phosphopantetheine = Facilitates acyl chain elongation Signup and view all the answers

Match the steps of acetyl-CoA carboxylase reaction with the corresponding outcomes:

Step 1: Carboxylation = Produces carboxylated biotin Step 2: Transfer of carboxyl group = Forms malonyl-CoA Decarboxylation = Pulls reactions forward ATP hydrolysis = Provides energy for carboxylation Signup and view all the answers

Match the following descriptions with the correct terms related to fatty acid synthesis:

Multienzyme complex = Coordination of enzyme synthesis by a single gene Homodimer = Consists of two identical polypeptide chains Compartmentalization = Isolates processes within the cell Enzyme activities = Six distinct catalytic functions within the complex Signup and view all the answers

Match the enzyme with its corresponding function in fatty acid synthesis:

Biotin carboxylase (E1) = Carboxylation of biotin Carboxyltransferase (E2) = Transfer of COO− to acetyl-CoA Ketoacyl synthase = Condensation of acetyl-CoA and malonyl-CoA Thioesterase = Release of free fatty acids Signup and view all the answers

Match the product with its corresponding reaction step:

Malonyl-CoA = Formation from acetyl-CoA Acetyl-CoA = Starting substrate for fatty acid synthesis NADPH = Reducing equivalent in synthesis process Fatty acids = End product after multiple cycles Signup and view all the answers

Match the enzyme domain with its corresponding role in the fatty acid synthase complex:

ACP = Carrier protein for acyl groups Ketoacyl reductase = Reduction of ketoacyl intermediates Enoyl reductase = Reduction of enoyl intermediates Hydratase = Introduction of water into the pathway Signup and view all the answers

Match the following substrates with their roles in the biochemical pathways:

Acetyl-CoA = Source of carbons for fatty acid synthesis Malonyl-CoA = Building block for fatty acid chains HCO3− = Source of the COO− group ATP = Energy currency used in carboxylation step Signup and view all the answers

Match the components of the fatty acid synthase complex with their descriptions:

Fatty acid synthase = Multienzyme complex involved in fatty acid synthesis Biotin carrier protein (BCP) = Connects biotin to the enzyme complex Dimer structure = Arrangement of two identical polypeptide monomers X-ray crystallography = Technique used to determine three-dimensional structure Signup and view all the answers

Study Notes

Biosynthesis of Fatty Acids & Eicosanoids

Fatty acids are synthesized by an extramitochondrial system.
Glucose is the primary substrate for lipogenesis in most mammals, but acetate is the main fuel in ruminants.
Inhibition of lipogenesis occurs in type 1 diabetes.
Polyunsaturated fatty acids (PUFAs) are important for maintaining cell membrane fluidity.
A high P:S ratio (polyunsaturated:saturated) in the diet is beneficial for preventing coronary heart disease.
Some fatty acids are essential and cannot be formed in the body.
The body needs specific dietary PUFAs to form eicosanoids (prostaglandins, thromboxanes, leukotrienes, lipoxins).
Fatty acid synthesis occurs in the cytoplasm of the liver, kidney, brain, lung, mammary gland, and adipose tissue.
This process requires NADPH, ATP, Mn²⁺, biotin, and bicarbonate (HCO₃⁻).
Acetyl-CoA is the substrate, and the final product is palmitate.

Initial & Controlling Step in Fatty Acid Synthesis

The initial step is the carboxylation of acetyl-CoA to form malonyl-CoA.
This step is catalyzed by acetyl-CoA carboxylase which requires ATP and biotin.
Acetyl-CoA carboxylase is a multi-enzyme protein containing biotin carboxylase, carboxyl transferase, and biotin carrier protein.
Malonyl-CoA is a key regulator in fatty acid synthesis.

Fatty Acid Synthase Complex

Fatty acids are formed by the fatty acid synthase enzyme complex.
The complex is a homodimer of two polypeptide chains, containing six enzymatic activities and acyl carrier protein (ACP).
ACP has a similar function like CoA in β-oxidation.
The complex is arranged in an X shape, increasing efficiency
The complex is encoded by a single gene.

The Main Pathway for De Novo Synthesis of Fatty Acids

The process that produces fatty acids from glucose and other substrates.
Occurs within the cytosol.
This requires NADPH, ATP, Mn²⁺, biotin, HCO₃⁻ as cofactors.
Acetyl CoA is the immediate building block and palmitic acid is the final product.

Main Source of NADPH for Lipogenesis

The pentose phosphate pathway is the main source.
Other sources include malate to pyruvate conversion catalyzed by NADP-dependent malate dehydrogenase (or malic enzyme).
Isocitrate dehydrogenase (specifically extramitochondrial) is a significant source in ruminants.

Acetyl-CoA is the Principal Building Block of Fatty Acids

Acetyl-CoA is initially formed from glucose in the mitochondrial matrix via pyruvate oxidation.
It cannot freely diffuse through the mitochondrial membrane.
Transport to the cytoplasm requires citrate's involvement.
Citrate is converted back into acetyl-CoA and oxaloacetate by ATP-citrate lyase.
This oxaloacetate can be used to regenerate acetyl-CoA and produce NADPH.

Elongation of Fatty Acid Chains

The microsomal (endoplasmic reticulum) system elongates fatty acyl-CoA molecules.
Uses malonyl-CoA as the 2-C donor unit.
NADPH is the reducing equivalent required.

Essential Fatty Acids (EFAs)

Some PUFAs are essential as they cannot be synthesized by humans.
Two major groups are w-6 and w-3 families.
Linoleic acid (w-6) and α-linolenic acid (w-3) are nutritionally essential to humans.

Eicosanoids

Derived from unsaturated 20-carbon fatty acids (eicosanoic acids).
Include prostaglandins, thromboxanes, leukotrienes, and lipoxins.
These are important for: inflammation, pain, sleep regulation, blood coagulation, and reproduction.
Cyclooxygenase (COX) pathway synthesizes prostaglandins and thromboxanes
Lipoxygenase pathway synthesizes leukotrienes and lipoxins.

Leukotrienes and Lipoxins

Formed by different lipoxygenase enzymes in response to stimuli.
Key inflammatory mediators, important for allergic and hypersensitivity reactions, vasculitis, bronchospasm, and chemotaxis.
Lipoxins are involved in resolution of inflammation.

Regulation of Lipogenesis

Factors like citrate (allosteric), phosphorylation/dephosphorylation, and hormonal factors (insulin, glucagon) regulate the process.
There are short-term and long-term regulatory mechanisms for lipogenesis
Acetyl-CoA carboxylase is a crucial regulatory enzyme.

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Description

This quiz covers the biosynthesis of fatty acids and eicosanoids, focusing on their metabolic pathways and importance in human health. It discusses the role of various substrates, essential fatty acids, and how dietary factors influence heart disease. Additionally, the quiz outlines the initial steps and controlling factors in fatty acid synthesis.