Lipid Biosynthesis and Metabolism

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Questions and Answers

What is the primary action of glucagon on adipocytes?

Decreases cAMP level, activating fatty acyl-CoA

Decreases cAMP level, inhibiting lipase activity

Increases cAMP level, activating lipase (correct)

Increases cAMP level, activating acetyl-CoA carboxylase

Which hormone is responsible for protein dephosphorylation in high blood sugar conditions?

Epinephrine

Insulin (correct)

Glucagon

Cortisol

What effect does malonyl-CoA have on fatty acyl-CoA?

Inhibits entry into mitochondria (correct)

Promotes entry into mitochondria

Activates acetyl-CoA carboxylase

Increases breakdown of fatty acids

Where does the synthesis of new membrane lipids primarily occur?

Smooth endoplasmic reticulum Signup and view all the answers

Which of the following describes glycerophospholipids?

Contain a glycerol backbone Signup and view all the answers

Which substance is NOT a source of acetyl-CoA for fatty acid synthesis?

Fatty Acids Signup and view all the answers

Which enzyme is specifically inhibited in bacteria to block fatty acid synthesis?

Enoyl-ACP reductase Signup and view all the answers

What is the fate of excess carbohydrates in the human body?

Converted to triacylglycerols Signup and view all the answers

What is a characteristic of animals regarding the introduction of double bonds in fatty acids?

They cannot introduce double bonds beyond C-9 Signup and view all the answers

Which process does NOT involve fatty acid metabolism regulation?

Conversion of glucose into nucleic acids Signup and view all the answers

What is the initial step in fatty acid elongation and desaturation?

Condensation of acyl-CoA Signup and view all the answers

What is the main role of triacylglycerols in the human body?

Fuel for energy-requiring processes Signup and view all the answers

What is the role of pyruvate dehydrogenase in fatty acid synthesis?

Catalyzes the conversion of pyruvate to acetyl-CoA Signup and view all the answers

What is the primary product of fatty acid synthesis after seven cycles?

Palmitic acid Signup and view all the answers

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

β-Ketoacyl-ACP synthase Signup and view all the answers

How many carbon atoms are added to the fatty acyl chain during each cycle of synthesis?

2 Signup and view all the answers

Which two residues are attachment points for acyl chains in the fatty acid synthase complex?

Cysteine and ACP Signup and view all the answers

What is produced during the reduction step following dehydration in the fatty acid synthesis pathway?

NADPH Signup and view all the answers

What is the role of palmityl thioesterase in fatty acid synthesis?

To cleave the fatty acyl chain from the ACP Signup and view all the answers

What is the total number of cycles required to synthesize a 16-carbon fatty acid chain?

7 cycles Signup and view all the answers

Which compound is essential for the condensation of acyl chains during the synthesis process?

Malonyl-CoA Signup and view all the answers

What is the main role of Acetyl-CoA carboxylase in fatty acid biosynthesis?

Catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA Signup and view all the answers

Which of the following statements about fatty acid biosynthesis is incorrect?

Fatty acids are synthesized in the mitochondria. Signup and view all the answers

What are the starting materials for the overall reaction to synthesize palmitic acid?

8 Acetyl-CoA, 7 ATP, and 14 NADPH Signup and view all the answers

What is a key metabolite produced during the carboxylation of acetyl-CoA?

Malonyl-CoA Signup and view all the answers

Which component is essential for the attachment of an acyl chain during the fatty acid synthesis process?

Phosphopantetheine group in Acyl Carrier Protein (ACP) Signup and view all the answers

What regulates lipid metabolism during varying blood glucose levels?

Insulin and glucagon levels Signup and view all the answers

Which lipids are synthesized through processes discussed in the content?

Cholesterol, triacylglycerols, and phospholipids Signup and view all the answers

What is the role of lovastatin and atorvastatin in cholesterol biosynthesis?

They are structural analogs of HMG-CoA and inhibit its reductase. Signup and view all the answers

How many isoprene units are needed for the formation of squalene?

4 Signup and view all the answers

Which process is NOT involved in the formation of cholesterol from squalene?

Decarboxylation reactions Signup and view all the answers

What are the potential fates of newly synthesized cholesterol?

Incorporated into membranes or used as a precursor for steroid hormones Signup and view all the answers

What substance is formed directly from the condensation of 6 isoprene units?

Squalene Signup and view all the answers

What is the precursor for Eicosanoids?

Arachidonic acid Signup and view all the answers

Which enzyme is the first in the biosynthesis of Eicosanoids?

Prostaglandin H2 synthase (COX) Signup and view all the answers

What differentiates COX-1 and COX-2?

They produce prostaglandins for different physiological functions. Signup and view all the answers

Which of the following statements is true about Vioxx?

It was withdrawn due to unanticipated cardiac side effects. Signup and view all the answers

What are thromboxanes primarily known for?

Inducing contraction of blood vessels. Signup and view all the answers

Which of the following is NOT a side effect of cyclooxygenase inhibition?

Reduced thromboxane production Signup and view all the answers

What is a characteristic of Salicylic acid?

It has severe stomach irritation as a side effect. Signup and view all the answers

Which of the following is NOT a function of Prostaglandins?

Regulating blood clotting Signup and view all the answers

Study Notes

Lipid Biosynthesis Learning Objectives

Lipid biosynthesis is vital for various functions
Fatty acid biosynthesis involves acetyl-CoA carboxylase and fatty acid synthase, encompassing chemical changes and utilizing ATP
Fatty acid elongation and desaturation processes are briefly explained
Conversion of carbohydrates and amino acids to fatty acids is described
Regulation of lipid metabolism correlates with blood glucose levels
Triacylglycerols, phospholipids, eicosanoids, and cholesterol biosynthesis are part of the overall process

Subcellular Lipid Metabolism Locations

Animal cells/yeast cells: Mitochondria are crucial for fatty acid oxidation, acetyl-CoA production, ketone body synthesis, and fatty acid elongation. The endoplasmic reticulum handles phospholipid and sterol synthesis (later stages), as well as fatty acid elongation and desaturation. The cytosol is where NADPH production (via pentose phosphate pathway and malic enzyme) occurs, along with earlier stages of isoprenoid/sterol synthesis and fatty acid synthesis. Malate is converted to pyruvate through a malic enzyme-catalyzed reaction, and NADP is converted to NADPH.
Plant cells: Chloroplasts are the site of NADPH and ATP production, and fatty acid synthesis. Glyoxysomes are involved in fatty acid oxidation.

Fatty Acid Biosynthesis

Fatty acids are synthesized in the cytosol, not a simple reversal of fatty acid oxidation
Palmitic acid (16:0) biosynthesis involves 8 acetyl-CoA, 7 ATP, 14 NADPH and 14 H⁺ molecules. The process ends up giving palmitic acid, 7ADP, 7Pi, 14 NADP⁺, 6H₂O and 8 coenzyme-A
Two enzymes are involved in this process: Acetyl-CoA Carboxylase and Fatty Acid Synthase

Acetyl-CoA Carboxylase (ACC)

ACC catalyses the carboxylation of acetyl CoA to yield malonyl CoA
This reaction is a committed step in fatty acid biosynthesis in animals

Fatty Acid Synthase (FAS) complex

FAS is a multi-enzyme protein complex with three polypeptides
Acyl Carrier Protein (ACP), a subunit, contains phosphopantetheine for acyl chain attachment
Cycles of condensation, reduction, dehydration and reduction reactions occur during acyl chain lengthening
The fatty acyl chain with 16 carbons is cleaved from ACP at the end of the reaction.

Triclosan

Triclosan, an antibacterial chemical, inhibits fatty acid synthesis by specifically blocking enoyl-ACP reductase.

Transport of acetyl-CoA

Acetyl-CoA is carried from the mitochondria into the cytosol for fatty acid synthesis via a tricarboxylate transport system.
Sources include pyruvate from glucose catabolism. The pyruvate is converted into Acetyl CoA

Elongation and Desaturation of Fatty Acids

Palmitate is the starting material for elongation and desaturation of longer-chain fatty acids, including stearate and oleate.
Elongation increases the number of carbons
Desaturation introduces double bonds

Essential Fatty Acids

Animals cannot synthesize certain fatty acids like linoleate and α-linolenate; thus, they are essential dietary components
Plants can produce a variety of polyunsaturated fatty acids from oleate. These can be further desaturated

Biosynthesis of Glycerophospholipids

Glycerophospholipids have a glycerol backbone
Two main pathways activate polar head groups (e.g., ethanolamine or choline) using CTP, producing CDP-ethanolamine or CDP-choline, respectively
The phosphoryl group then attacks CTP, forming CDP-ethanolamine or CDP-choline. The PPi product is further hydrolyzed
The activated head groups are transferred to diacylglycerol to generate the glycerophospholipids.

Biosynthesis of Sphingolipids

Sphingolipids have a sphinganine backbone (a C18 amino alcohol)
Palmitoyl-CoA and serine are the starting materials
Several reactions (including 3-ketosphinganine synthase, 3-ketodihydrosphingosine reductase) lead to sphinganine
N-acylsphinganine (dihydroceramide) is then formed from sphinganine through acyl-CoA transferase
Further reactions produces ceramide, a precursor to other sphingolipids
Different sphingolipids (like sphingomyelin and gangliosides) are produced by adding different polar head groups to ceramide

Biosynthesis of Eicosanoids

Eicosanoids are potent signaling molecules derived from arachidonic acid
Examples include prostaglandins (pain and inflammation regulators) and thromboxanes (involved in blood clotting)

Prostaglandin H₂ synthase (COX)

COX is involved in eicosanoid synthesis
It has two catalytic activities: cyclooxygenase and peroxidase
Two isoforms exist (COX-1 and COX-2), with different functions

Different Pain Killers/Anti-inflammatory Drugs Targeting COX

Drugs target COX enzymes, inhibiting inflammation
Aspirin (acetylsalicylic acid) is a common example
Other drugs include ibuprofen, rofecoxib (Vioxx), and celecoxib (Celebrex)

Salicylic Acid

Salicylic acid is a natural pain-reliever found in willow bark
Structurally related to aspirin
Naturally, plant hormones suppress diseases and wilting

Cholesterol Biosynthesis

Cholesterol biosynthesis is a complex process with several steps
The process starts from squalene and involves reactions to form cholesterol
Multiple enzymes and intermediate molecules are involved in cholesterol biosynthesis

Cholesterol-Lowering Drugs

Drugs that lower cholesterol (e.g., lovastatin and atorvastatin) are structural analogs of HMG-CoA. They competitively inhibit the enzyme HMG-CoA reductase.

Fates of Newly Synthesized Cholesterol

Newly synthesized cholesterol can be incorporated into the cell membrane
It can be used to make steroid hormones like testosterone and estrogen
Cholesterol is packaged as a cholesteryl ester in lipoproteins.

Summary of Lipid Metabolism

Triacylglycerol, phospholipid/sphingolipid, eicosanoid, and cholesterol metabolism are outlined in a comprehensive diagram.
Metabolism of these molecules all link to Carbohydrates via Acetyl CoA and oxidative phosphorylation.

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Description

Explore the essential processes of lipid biosynthesis, including fatty acid synthesis and its regulation in relation to glucose levels. This quiz covers the various pathways involved in lipid metabolism across different subcellular locations, such as mitochondria and the endoplasmic reticulum. Test your knowledge on key enzymes and the conversion processes of nutrients into lipids.