Advanced Biochemistry - Metabolism 45 questions assignment

KarolZL

3-20-Biol5311Ch20Lipidmetabol2018.pdf

Home >Biology homework help >Advanced Biochemistry - Metabolism 45 questions assignment

Fundamentals of Biochemistry

Fourth Edition

Chapter 20 Lipid Metabolism

Donald Voet • Judith G. Voet • Charlotte W. Pratt

The Red Knot will migrate approximately 10,000 miles /year! During migration, it gets water by oxidizing stored fat while staying in flight for days at a time.

Elephant seals gather on the central CA coast for mating and calving Jan-Feb each year. They will not eat for 2 months, surviving on stored fat.

Chapter 20 Lipid Digestion, Absorption, & Transport

Key Concepts 20.1 • Triacylglycerols are broken down by lipases, and the products are absorbed by the intes8ne. • Lipoproteins transport lipids between the intes8nes, liver, and other 8ssues.

Major Bile Acids & Conjugates

Triacylglycerol

Lipases Act at Lipid-Water Interface

Pancrea3c lipase PDBids 1N8S and 1LPB

Phospholipase A2-Micelle Complex

Fatty Acid-Binding Protein Binds Lipids

Rat intes3nal fa?y acid-binding protein PDBid 2IFB

air

chemical break down of fat

Lipoproteins in Human Plasma

air

name- where they run in density in ultracentrifuge

LDL

Apolipoprotein A-I

Human apolipoprotein A-I PDBid 1AV1

Apolipoprotein A-I

air

delta G= -nFdeltaE- also know the unit

air

products of photosynethsis is G3P not glucose

Triacylglycerol & Cholesterol Transport

Receptor-Mediated Endocytosis of LDL

Chapter 20 Lipid Digestion, Absorption, & Transport

Checkpoint 20.1 • How do lipases access their substrates? • Explain the purpose of bile acids and faAy acid–binding protein in the diges8on and absorp8on of lipids. • Describe the overall structure of lipoproteins. What dis8nguishes the different types? • Summarize the roles of the various lipoproteins in transpor8ng triacylglycerols and cholesterol. • What is the importance of lipoprotein lipase? • Describe the process of receptor-mediated endocytosis of LDL.

Chapter 20 Fatty Acid Oxidation

Key Concepts 20.2 • FaAy acids to be degraded are linked to CoA in an ATP -dependent reac8on. • FaAy acyl groups are transported into the mitochondrion via a carni8ne shuAle for oxida8on. • Each round of mitochondrial β oxida8on produces FADH2, NADH, and acetyl-CoA. • Addi8onal enzymes are required to oxidize unsaturated faAy acids. • The propionyl-CoA produced by the oxida8on of odd-chain faAy acids is converted to succinyl-CoA. • Peroxisomes oxidize long-chain faAy acids, producing H2O2.

Elucidating the Fatty Acid Oxidation Pathway

air

can break down any further

Acyl-CoA Synthetase Mechanism

air

cytoplasma

Carnitine Carries Acyl Groups Across Mitochondrial Membrane

air

in animal cell

Carnitine Carries Acyl Groups Across Mitochondrial Membrane

β Oxidation of Fatty Acyl-CoA

air

hydro this double bond

air

made double bond

β Oxidation of Fatty Acyl-CoA

air

oxidase COH

β Oxidation of Fatty Acyl-CoA

Active Site: Medium-Chain Acyl-CoA Dehydrogenase

Acyl-CoA dehydrogenase PDBid 3MDE

β-ketoacyl-CoA Thiolase Mechanism

Unsaturated Fatty Acids

Oxidation of Unsaturated Fatty Acids

air

cis-double

Oxidation of Unsaturated Fatty Acids

air

requires a trans double bond

Oxidation of Unsaturated Fatty Acids

Propionyl-CoA to Succinyl-CoA

Skeletal Rearrangement Catalyzed by Methylmalonyl-CoA Mutase

5`-Deoxyadenosylcobalamin

air

B12

Methylmalonyl-CoA Mutase

P. shermanii methylmalonyl-CoA mutase PDBid 7REQ

Methylmalonyl-CoA Mutase Mechanism

air

allow

Succinyl-CoA Not Directly Consumed by CAC

Peroxisome Surrounded by Rough ER

air

very long chain, >18 carbon

air

in plants, all fat in peroxisome

Chapter 20 Fatty Acid Oxidation

Checkpoint 20.2 • Describe the ac8va8on of faAy acids. What is the energy cost for the process? • How do cytosolic acyl groups enter the mitochondrion for degrada8on? • Summarize the chemical reac8ons that occur in each round of β oxida8on. Explain why the process is called β oxida8on. • How is ATP recovered from the products of β oxida8on? • What addi8onal steps are required to oxidize unsaturated and odd-chain faAy acids? • What is unusual about the methylmalonyl-CoA mutase structure and the reac8on it catalyzes? • Describe the differences between peroxisomal and mitochondrial β oxida8on.

Chapter 20 Ketone Bodies

Key Concepts 20.3 • Acetyl-CoA may be reversibly converted to ketone bodies in the liver to be used as fuel by other 8ssues.

Ketone Bodies

Ketogenesis

β-Hydroxybutyrate Dehydrogenase

Ketone Bodies to Acetyl-CoA

Chapter 20 Ketone Bodies

Checkpoint 20.3 • What are ketone bodies? • How are they synthesized and degraded?

Chapter 20 Fatty Acid Biosynthesis

Key Concepts 20.4 • The tricarboxylate transport system transfers acetyl-CoA into the cytosol for faAy acid synthesis. • FaAy acid synthesis begins with the carboxyla8on of acetyl -CoA to generate malonyl-CoA. • FaAy acid synthase carries out seven reac8ons and lengthens a faAy acid two carbons at a 8me. • Elongases and desaturases may modify faAy acids. • Triacylglycerols are synthesized from glycerol and faAy acids.

air

in plants—> plastids

air

cytosol? mitochondria

Fatty Acid β Oxidation & Biosynthesis Compared

air

break down

air

synthesis

Tricarboxylate Transport System

Acetyl-CoA Carboxylase (ACC) Reaction

air

first

Phosphopantetheine Groups

Decarboxylation Drives β-ketoacyl-ACP Synthase

Biosynthesis of Fatty Acids

Domain Organization of Fatty Acid Synthase

Structure of Fatty Acid Synthase

Mammalian fa?y acid synthase PDBid 2VZ9

air

a singe amino acid chain

Box 20-3: Polyketide Synthesis

Mitochondrial Fatty Acid Elongation

Triacylglycerol Synthesis

Lipid Metabolism Summary

air

if start with Acdtyl coA cannot make glucose if animal

Chapter 20 Fatty Acid Biosynthesis

Checkpoint 20.4 • Compare the shuAle systems for transpor8ng faAy acids into the mitochondria and acetyl-CoA into the cytosol. • What is the role of ATP-citrate lyase in faAy acid synthesis? • Describe the reac8ons that produce and consume malonyl -CoA during faAy acid synthesis. • Why does it make metabolic sense for the cell to regulate the ac8vity of acetyl-CoA carboxylase?

Chapter 20 Fatty Acid Biosynthesis

Checkpoint 20.4 • Summarize the reac8ons catalyzed by faAy acid synthase and compare them to the reac8ons of faAy acid oxida8on. • Describe the role of mul8func8onal enzymes in both faAy acid synthesis and oxida8on. • What are the purposes of elongases and desaturases? Where are the enzymes located? • Describe how newly synthesized faAy acids are incorporated into triacylglycerols.

Chapter 20 Regulation of Fatty Acid Metabolism

Key Concepts 20.5 • FaAy acid oxida8on and synthesis are regulated by hormones and cellular factors.

Regulation Sites of Fatty Acid Metabolism

Chapter 20 Regulation of Fatty Acid Metabolism

Checkpoint 20.5 • How do hormones link fuel availability to faAy acid synthesis and degrada8on in humans? • Explain how malonyl-CoA produc8on can regulate faAy acid metabolism.

Chapter 20 Synthesis of Other Lipids

Key Concepts 20.6 • The triacylglycerol precursors diacylglycerol and phospha8dic acid are used to synthesize glycerophospholipids. • Sphingolipids are synthesized from palmitoyl-CoA and serine. • Prostaglandin synthesis from arachidonate can be blocked by drugs.

Glycerolipids & Sphingolipids

Diacylglycerophospholipid Biosynthesis

Phosphatidylserine Biosynthesis

Cardiolipin Biosynthesis

Phosphatidylinositol & Phosphatidylglycerol

Plasmalogens & Alkylacylglycerophospholipids

Ceramide Biosynthesis

Sphingomyelin

Prostaglandin H2 Synthase Reaction

Prostaglandin H2 Synthase Inhibitors

Cox-2 Inhibitors

Box 20-4: Sphingolipid Degradation & Storage Diseases

Chapter 20 Synthesis of Other Lipids

Checkpoint 20.6 • Where are membrane lipids synthesized? • Explain how glycerophospholipids are synthesized by ac8va8ng either the head group or the lipid tail. • Describe the biosynthesis of ceramide, sphingomyelin, and cerebrosides. • Explain the ac8on of drugs such as aspirin, NSAIDs, and coxibs.

Chapter 20 Cholesterol Metabolism

Key Concepts 20.7 • The liver converts acetyl-CoA to cholesterol by a mul8step pathway. • Cholesterol synthesis is regulated by the ac8vity and amount of HMG-CoA reductase. • The LDL receptor keeps circula8ng cholesterol low.

Cholesterol: Acetyl-CoA is Converted to Isoprene Units

Pyrophosphomevalonate Decarboxylase Reaction

Isopentenyl Pyrophosphate Isomerase Reaction

Prenyltransferase Reaction Mechanism

HMG-CoA to Isopentenyl Pyrophosphate

Squalene Formation

Squalene Epoxidase Reaction

Cholesterol Precursor, Lanosterol

Cholesteryl Ester

Oxidosqualene Cyclase Reaction

Cholesterol-Mediated SREBP Activation

HMG-CoA Reductase Inhibitors

Atherosclerotic Plaque

Role of LDL & HDL

Chapter 20 Cholesterol Metabolism

Checkpoint 20.7 • Describe the types of reac8ons required to produce a molecule of cholesterol. • How does cholesterol control its own synthesis? • How do sta8ns reduce cholesterol levels? • What do familial hypercholesterolemia and Tangier disease reveal about the development of atherosclerosis?

Copyright 2016 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of these programs or from the use of the information herein.