54. Biochemistry -- Lipid Metabolism I Synthesis of Palmitate & Related Molecules

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Questions and Answers

What is the maximum carbon length at which humans can insert a double bond in fatty acids?

6 carbons

18 carbons

12 carbons

9 carbons (correct)

Which fatty acids are classified as essential components of the human diet due to their role in synthesizing polyunsaturated fatty acids?

Linoleic acid and Alpha-linolenic acid (correct)

Palmitic acid and Linoleic acid

Oleic acid and Stearic acid

Arachidonic acid and Eicosapentaenoic acid

What is arachidonate derived from?

Oleic acid

Stearic acid

Palmitate

Linoleate (correct)

Which of the following options correctly identifies the role of eicosanoids?

They exert effects on nearby cells and are involved in inflammatory responses. Signup and view all the answers

How do humans synthesize the full complement of polyunsaturated fatty acids from linoleic acid and alpha-linolenic acid?

Through elongation and desaturation mechanisms proximal to C-9. Signup and view all the answers

Which of the following is NOT a classification of eicosanoids?

Cholesterols Signup and view all the answers

What is the effect of inserting double bonds in fatty acids on their melting temperature?

Increase melting temperature, disfavoring bilayer fluidity. Signup and view all the answers

Which tissue primarily utilizes arachidonate for the synthesis of eicosanoids?

Phosphoglycerol membranes Signup and view all the answers

What is the primary functional role of Acetyl-CoA in lipid metabolism?

It is an intermediate for both lipid and carbohydrate metabolism. Signup and view all the answers

Which fatty acid typically has a carbon chain length that is physiologically significant?

16-18 carbons Signup and view all the answers

What is the role of pyrophosphatases in biochemical reactions?

Assisting in group transfer reactions by hydrolyzing pyrophosphate. Signup and view all the answers

What is the significance of Linoleate and a-Linolenate in fatty acid metabolism?

They are essential fatty acids that must be obtained from the diet. Signup and view all the answers

What is the primary role of Acetyl-CoA in palmitate synthesis?

It provides the carbon skeleton for palmitate. Signup and view all the answers

What is a primary function of the ketoacyl synthase activity within the fatty acid synthase complex?

To condense acetyl units into a growing fatty acid chain. Signup and view all the answers

Which enzyme is primarily responsible for increasing the chemical reactivity of Acetyl-CoA?

Acetyl-CoA Carboxylase Signup and view all the answers

Which of the following statements about cyclooxygenases COX-1 and COX-2 is true?

COX-1 is primarily involved in the production of prostaglandins for homeostasis. Signup and view all the answers

What is the role of phosphopantetheine in fatty acid synthesis?

It acts as an acyl group carrier during fatty acid synthesis. Signup and view all the answers

Which process provides the majority of NADPH required for palmitate synthesis?

Citrate shuttle Signup and view all the answers

What is the mechanism through which malate can generate NADPH during fatty acid synthesis?

By undergoing oxidative decarboxylation Signup and view all the answers

What is a key step in the fatty acid synthesis cycle?

Hydrolytic release of palmitate. Signup and view all the answers

In palmitate synthesis, how many times is the enzyme-catalyzed process repeated to produce a full chain?

What is the function of the citrate transporter in fatty acid synthesis?

To transport citrate out of mitochondria Signup and view all the answers

What transformation occurs during the first step of the enzyme-catalyzed process of fatty acid elongation?

Condensation with an activated acetyl unit Signup and view all the answers

Which best describes the role of pyruvate in the fatty acid synthesis pathway?

Transported between mitochondria and the cytoplasm Signup and view all the answers

What is the role of Acetyl Transferase in the fatty acid synthesis process?

It transfers an acetyl group to the KS site cysteine. Signup and view all the answers

During which reaction does a carboxylate bond break, releasing CO2?

Beta-Ketoacyl Synthase reaction. Signup and view all the answers

What compound is used to provide reducing equivalents in the Beta-Ketoacyl Reductase reaction?

NADPH. Signup and view all the answers

What happens during the Beta-Hydroxyacyl Dehydratase reaction?

Water is removed to create an enoyl derivative. Signup and view all the answers

Which of the following enzymes is responsible for hydrolyzing the thioester bond between palmitate and ACP?

Thioesterase. Signup and view all the answers

What is formed after the Beta-Enoyl Reductase reaction?

AcylC4-ACP. Signup and view all the answers

What initiates the fatty acid synthesis by providing the first carbon to the FAS?

Acetyl-CoA. Signup and view all the answers

Which intermediate is attached to phosphopantetheine during the fatty acid synthesis?

All of the above. Signup and view all the answers

What is the primary reason corticosteroids are considered anti-inflammatory?

They inhibit the gene expression for PLA2. Signup and view all the answers

Which statement correctly differentiates between COX-1 and COX-2?

COX-1 maintains gastrointestinal integrity, while COX-2 expression increases in inflammatory states. Signup and view all the answers

What is the consequence of inhibiting thromboxane synthesis in blood platelets?

Reduced ability to form blood clots. Signup and view all the answers

Which enzymatic activity is NOT associated with PGH2 Synthase?

Phospholipase activity. Signup and view all the answers

What is the main role of lipoxygenases in arachidonate metabolism?

Catalyze leukotriene synthesis from arachidonate. Signup and view all the answers

Which of the following statements about NSAIDs is incorrect?

NSAIDs permanently bind to COX-1 and COX-2. Signup and view all the answers

Which condition typically results in increased levels of COX-2 expression?

Inflammatory diseases. Signup and view all the answers

Why is aspirin considered effective for long-term inhibition of thromboxane synthesis in platelets?

Platelets lack a nucleus and cannot synthesize new COX enzymes. Signup and view all the answers

Study Notes

All Lipids are Derived from Acetyl-CoA

Acetyl-CoA is an activated form of acetic acid
It is a high-energy intermediate due to the thioester bond
Acetyl-CoA plays a central role in lipid metabolism just like G6P in carbohydrate metabolism

Fatty Acid (FA) Structure and Nomenclature

Fatty acids are monocarboxylic hydrocarbons with varying carbon chain lengths (5-26 carbons)
Physiologically important FAs typically have chain lengths of 16-18 carbons
Palmitate (16:0) is the primary product of de novo FA synthesis

Key Points about Fat Synthesis

Palmitate synthesis requires Acetyl-CoA, ATP, NADPH, and two enzymes: Acetyl-CoA Carboxylase and Fatty Acid Synthase
All palmitate carbons originate from Acetyl-CoA, added two carbons at a time
Fatty acid synthesis takes place in the cytoplasm

Transfer of Acetyl-CoA from Mitochondrial Matrix to Cytosol

Acetyl-CoA is produced in the mitochondrial matrix
There is no membrane carrier for acetyl-CoA, but there is a carrier for citrate
The Citrate Shuttle allows the continuous production of citrate in mitochondria and its cleavage in the cytoplasm

Acetyl-CoA Carboxylase: Activating the Acetyl Methyl Carbon

Acetyl-CoA carboxylase catalyzes the carboxylation of acetyl-CoA to malonyl-CoA
This activation step is required for the elongation of fatty acid chains

Palmitate (C16:0 FA) Synthesis by the Multifunctional Fatty Acid Synthase (FAS)

Phosphopantetheine acts as an acyl group carrier during fatty acid synthesis
FAS is a multifunctional enzyme with distinct domains responsible for specific reactions
The FAS reaction cycle involves 7 repeated rounds of elongation and reduction
The cycle is initiated by priming with acetyl-CoA
The cycle involves recursive rounds of elongation and reduction
The process concludes with hydrolytic release of palmitate

Alternate FA Products of the FAS

FAS can also produce alternate FA products like myristate (C14:0) and stearate (C18:0)

Fatty Acid Neutralization and Activation for Group Transfer Reactions

Newly synthesized fatty acids need to be activated for further metabolism
Activation involves the attachment of CoA to form fatty acyl-CoA

Fatty Acid Elongation and Desaturation

After palmitate synthesis, fatty acids can be elongated and desaturated
Elongation adds two carbons to the fatty acid chain
Desaturation introduces double bonds into the fatty acid chain

Essential Fatty Acids: Linoleate and α-linolenate

Linoleate (ω-6 FA) and α-linolenate (ω-3 FA) are essential fatty acids
They contain double bonds beyond carbon-9, which cannot be introduced by human enzymes

Fatty Acid-Derived Signaling Molecules: Eicosanoids

Eicosanoids are a family of short-lived signaling molecules
They act as local hormones, exerting effects on nearby cells
Eicosanoid classes include prostaglandins, leukotrienes, thromboxanes, prostacyclins, and epoxyeicosatrienoic acids

Prostaglandin H2 Synthases (COX-1 and COX-2)

COX-1 is constitutively expressed in most cell types
COX-2 expression is regulated and increases during inflammation
COX-1 is important for thromboxane formation in platelets and GI integrity
COX-2 is involved in inflammation, and its inhibition is a target for anti-inflammatory therapy

COX Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin inhibit COX activity
Most NSAIDs inhibit both COX-1 and COX -2
Selective COX-2 inhibitors, like Celebrex and Vioxx, have been developed

Mobilization of Arachidonate

Arachidonate is a 20-carbon, polyunsaturated ω-6 FA derived from linoleate
It is frequently found in phosphoglycerol membrane lipids
Phospholipase A2 releases arachidonate from membrane phospholipids
Corticosteroids inhibit PLA2 activity, reducing arachidonate release

Products of Linear and Cyclic Pathways

Lipoxygenases catalyze the synthesis of leukotrienes from arachidonate (linear pathway)
PGH2 Synthase catalyzes the synthesis of prostaglandin H2 from arachidonate (cyclic pathway)
PGH2 is then converted into other prostaglandins, prostacyclins, and thromboxanes
PGH2 Synthase is also known as cyclooxygenase (COX) due to its cyclization activity
COX is a heme-containing dioxygenase, bound to ER membranes.

Two Isoforms of COX

COX-1 is constitutively expressed and is essential for thromboxane formation and GI integrity
COX-2 is inducible and is involved in inflammation
Aspirin irreversibly inhibits both COX-1 and COX -2, reducing prostaglandin and thromboxane synthesis
Selective COX-2 inhibitors are used to treat inflammatory diseases while minimizing GI side effects

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Description

Explore the essential role of Acetyl-CoA in lipid metabolism and the structure and nomenclature of fatty acids. Understand key points about fatty acid synthesis, including the importance of enzymes and cellular location. This quiz will deepen your knowledge of biochemistry concepts related to lipids and energy metabolism.