LDL Receptor-Mediated Endocytosis

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Questions and Answers

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

To transport acetyl-CoA from the cytosol to the mitochondrion

To convert acetyl-CoA to malonyl-CoA

To transport acetyl units from the mitochondrion to the cytosol (correct)

To catalyze the formation of C-C bonds

What is the first committed step in fatty acid biosynthesis from acetyl-CoA?

The transport of acetyl units to the cytosol

The conversion of acetyl-CoA to citrate

The synthesis of malonyl-CoA (correct)

The formation of C-C bonds

What is the name of the enzyme that catalyzes the synthesis of malonyl-CoA from acetyl-CoA?

Acetyl-CoA carboxylase (ACC) (correct)

Fatty acid synthase

Malonyl-CoA decarboxylase

Citrate synthase

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

To represent an activated source of two-carbon fragments Signup and view all the answers

In which cellular location does fatty acid synthesis occur in eukaryotes?

Cytosol Signup and view all the answers

What is the primary difference between fatty acid synthesis and fatty acid oxidation?

All of the above Signup and view all the answers

What is the name of the complex that carries out fatty acid synthesis in eukaryotes?

Megasynthase Signup and view all the answers

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

To provide a source of two-carbon fragments for fatty acid synthesis Signup and view all the answers

What is the role of albumin in the transport of fatty acids in the blood plasma?

To bind and transport fatty acids to the liver and other tissues Signup and view all the answers

What is the effect of phosphorylation of perilipin (PL) during lipolysis?

It dissociates CGI-58 from the lipid droplet Signup and view all the answers

What is the final product of the breakdown of fatty acids with an even-numbered carbon chain in Knoop's experiment?

Phenylacetic acid Signup and view all the answers

What is the role of protein kinase A (PKA) in the control of lipolysis?

It phosphorylates and activates HSL Signup and view all the answers

What is the function of glycerol released from adipose cells during lipolysis?

It serves as a substrate for gluconeogenesis Signup and view all the answers

What is the sequence of lipases involved in the hydrolysis of triacylglycerols (TG) during lipolysis?

ATGL, HSL, MGL Signup and view all the answers

What is the role of CGI-58 in the activation of ATGL?

It binds and recruits ATGL to the lipid droplet Signup and view all the answers

What is the effect of hormonal activation of a β-adrenergic G-protein coupled receptor on lipolysis?

It increases the activity of protein kinase A (PKA) Signup and view all the answers

What is a key event in atherogenesis?

Uptake of oxidized LDL by a scavenger receptor Signup and view all the answers

What is the role of cAMP-dependent phosphorylation in adipose cells?

It activates lipolytic enzymes Signup and view all the answers

What is the function of clathrin in coated pits?

It forms triskelions that assemble into polyhedral lattices Signup and view all the answers

What is the result of receptor-mediated endocytosis of LDL?

Formation of an endocytotic vesicle Signup and view all the answers

What is the correlation between PUFA ingestion and plasma cholesterol levels?

PUFA ingestion is correlated with low plasma cholesterol levels Signup and view all the answers

What is the role of LDL receptors in cholesterol metabolism?

They are involved in cholesterol uptake and metabolism Signup and view all the answers

What is the purpose of conjugating LDL with ferritin?

To permit electron microscopic visualization Signup and view all the answers

What is the structure of a clathrin-coated pit?

A polyhedral lattice composed of hexagons and pentagons Signup and view all the answers

What is the precursor to all steroids?

Cholesterol Signup and view all the answers

What is the configuration of the hydrogens at positions 5, 9, and 14 in the steroid ring system?

a-configuration Signup and view all the answers

How many carbons are derived from acetate in the formation of isoprene?

5 Signup and view all the answers

What is the product of the cyclization of the linear hydrocarbon squalene?

Cholesterol Signup and view all the answers

What is the number of C6 mevalonates converted to squalene in cholesterol biosynthesis?

6 Signup and view all the answers

What is the process of converting acetate to a C6 isoprenoid precursor in cholesterol biosynthesis?

Conversion of C2 fragments to mevalonate Signup and view all the answers

What is the term for the configuration of substituents that project below the plane of the steroid ring system?

a-configuration Signup and view all the answers

What is the term for the configuration of substituents that project above the plane of the steroid ring system?

b-configuration Signup and view all the answers

What is the result of the third phosphorylation of mevalonate?

Decarboxylation to give a five-carbon compound Signup and view all the answers

What is the role of NADPH in the conversion of farnesyl pyrophosphate to squalene?

Hydride transfer to complete the rearrangement Signup and view all the answers

What is the effect of sterol binding on HMG-CoA reductase?

Rapid degradation of the enzyme Signup and view all the answers

What is the mechanism of action of statins in lowering blood cholesterol levels?

Competitively inhibiting HMG-CoA reductase Signup and view all the answers

What is the product of the decarboxylation reaction of mevalonate?

Isopentenyl pyrophosphate Signup and view all the answers

What is the role of the double bond in the conversion of farnesyl pyrophosphate to squalene?

Nucleophilic attack on the allylic carbocation Signup and view all the answers

What is the result of the loss of a proton from C1 of the farnesyl-PPi molecule?

Formation of the activated cyclopropane intermediate Signup and view all the answers

What type of compounds are lovastatin and simvastatin?

Fungal polyketides Signup and view all the answers

Study Notes

Receptor-Mediated Endocytosis of LDL

LDL was conjugated with ferritin to permit electron microscopic visualization, allowing the study of its uptake by a scavenger receptor.
The LDL-ferritin complex binds to a coated pit on the surface of a cultured human fibroblast, which then forms an endocytotic vesicle.
Clathrin, the major protein in coated pits, forms triskelions that assemble into polyhedral lattices, composing a cage-like structure.

Involvement of LDL Receptors in Cholesterol Uptake and Metabolism

LDL receptors play a crucial role in cholesterol uptake and metabolism.
Polyunsaturated fat (PUFA) ingestion is correlated with low plasma cholesterol levels, although the mechanisms involved are not fully understood.

Mobilization of Adipose Cell Triacylglycerols by Lipolysis

Lipolysis is the process of hydrolyzing triacylglycerols (TG) to glycerol and free fatty acids (FFA) in adipose cells.
Three lipases act sequentially to hydrolyze TG: lipase, hormone-sensitive lipase (HSL), and monoacylglycerol lipase (MGL).
Exported FFA is bound to albumin for transport to liver and other tissues for oxidation.
Glycerol is released to the blood and taken up by liver cells, where it serves as a gluconeogenic substrate.

Control of Lipolysis in Adipose Cells

Lipolysis is controlled by a cAMP-mediated cascade system, involving hormonal activation of a β-adrenergic G-protein coupled receptor.
cAMP activates protein kinase A (PKA), which phosphorylates perilipin (PL) and HSL, leading to the recruitment of ATGL and the hydrolysis of TG.

Fatty Acid Oxidation

Knoop's experiments demonstrated the β-oxidation of fatty acids, showing that even-numbered carbon chains result in phenylacetic acid, while odd-numbered chains result in benzoic acid.

Biosynthesis of Ketone Bodies

When carbohydrate catabolism is limited, acetyl-CoA is converted to ketone bodies, mainly acetoacetate and β-hydroxybutyrate, in the liver.

Fatty Acid Biosynthesis

Acetyl-CoA is the key intermediate between fat and carbohydrate metabolism, and citrate serves as a carrier to transport acetyl units from the mitochondrion to the cytosol for fatty acid synthesis.
The synthesis of malonyl-CoA from acetyl-CoA and bicarbonate is the first committed step in fatty acid biosynthesis.
Malonyl-CoA represents an activated source of two-carbon fragments for fatty acid biosynthesis, with the loss of CO2 driving C-C bond formation.

Chemical Similarities between Oxidation and Synthesis of a Fatty Acid

The chemical similarities between fatty acid oxidation and synthesis are due to the involvement of similar intermediates and electron carriers.

Structure and Swinging Arm Mechanism in the Mammalian Fatty Acid Synthase Complex

The fatty acid synthase complex is an organized multienzyme complex that contains multifunctional proteins.
The complex includes a swinging arm mechanism, where the activated acyl group is transferred between different active sites.

Steroid Metabolism

The five carbons of isoprene could be derived metabolically from three molecules of acetate.
Cholesterol biosynthesis can be considered as three distinct processes: conversion of C2 fragments to a C6 isoprenoid precursor, conversion of six C6 mevalonates to the C30 squalene, and cyclization of squalene to the C27 cholesterol.
The biosynthesis of mevalonate and its conversion to isopentenyl pyrophosphate and dimethylallyl pyrophosphate involve a series of phosphorylations and decarboxylations.
The conversion of farnesyl pyrophosphate to squalene is catalyzed by squalene synthase, involving a cyclopropane intermediate and hydride transfer from NADPH.

Regulation of HMG-CoA Reductase

HMG-CoA reductase is regulated by ubiquitin-mediated proteolysis, where sterol binding leads to rapid degradation of the enzyme.
Statins, such as lovastatin and simvastatin, are specific inhibitors of HMG-CoA reductase, acting by competitive inhibition.

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Description

Learn about the role of LDL receptor density in atherogenesis and fat mobilization, including receptor-mediated endocytosis of LDL and its conjugation with ferritin for electron microscopic visualization.