Biochemistry of Lipids, Lipoproteins and Membranes

Neale Ridgway, Roger McLeod, J.E. Vance, Dennis E. Vance

• Publisher: Elsevier Science
• Year: 2008
• eBook ISBN: 9780080559889
• Edition: 5
• Topic: Biological Sciences
• Subtopic: Biochemistry
• Index: Biological Sciences

Research on the biochemistry and molecular biology of lipids and lipoproteins has experienced remarkable growth in the past 20 years, particularly with the realization that many different classes of lipids play fundamental roles in diseases such as heart disease, obesity, diabetes, cancer and neurodegenerative disorders. The 5th edition of this book has been written with two major objectives. The first objective is to provide students and teachers with an advanced up-to-date textbook covering the major areas of current interest in the lipid field. The chapters are written for students and researchers familiar with the general concepts of lipid metabolism but who wish to expand their knowledge in this area. The second objective is to provide a text for scientists who are about to enter the field of lipids, lipoproteins and membranes and who wish to learn more about this area of research. All of the chapters have been extensively updated since the 4th edition appeared in 2002.- Represents a bridge between the superficial coverage of the lipid field found in basic biochemistry text books and the highly specialized material contained in scientific review articles and monographs- Allows scientists to become familiar with recent developments related to their own research interests, and will help clinical researchers and medical students keep abreast of developments in basic science that are important for subsequent clinical advances- Serves as a general reference book for scientists studying lipids, lipoproteins and membranes and as an advanced and up-to-date textbook for teachers and students who are familiar with the basic concepts of lipid biochemistry

CHAPTER 1

Functional roles of lipids in membranes

William Dowhan, [email protected], Mikhail Bogdanov and Eugenia Mileykovskaya, Department of Biochemistry and Molecular Biology, University of Texas-Houston, Medical School, 6431 Fannin, Suite 6.200, Houston, TX 77030, USA, Tel.: [phone]; Fax: [phone]

Publisher Summary

Biological membranes due to the lipid component are flexible self-sealing boundaries that form the permeability barrier for cells and organelles. They provide the means to compartmentalize functions, but at the same time they perform many other duties. As a support for both integral and peripheral membrane processes, the physical properties of the lipid component directly affect these processes in ways that are often difficult to assess. Each specialized membrane has a unique structure, composition, and function. Within each membrane exists microdomains such as lipid rafts, lipid domains, and organizations of membrane-associated complexes with their own unique lipid composition. Lipids provide the complex hydrophobic-hydrophilic solvent within which membrane proteins fold and function, and they act in a more specific manner in determining the final membrane protein organization and orientation in the membrane. These diverse functions of lipids are made possible by a family of low-molecular-weight molecules that are physically fluid and deformable to enable interaction in a flexible and specific manner with other macromolecules. Defining lipid function is a challenging undertaking because of the diversity of the chemical and physical properties of lipids and the fact that each lipid type potentially is involved at various levels of cellular function.

Contents

1. Introduction and overview

2. Diversity in lipid structure

2.1. Glycerolipids

2.2. Saccharolipids

2.3. Sphingolipids

3. Properties of lipids in solution

3.1. Why do polar lipids self-associate?

3.2. Physical properties of membrane bilayers

3.3. Special properties of CL

3.4. What does the membrane bilayer look like?

4. Engineering of membrane lipid composition

4.1. Alteration of lipid composition in bacteria

4.2. Alteration of lipid composition in yeast

5. Role of lipids in cell function

5.1. The bilayer as a supermolecular lipid matrix

5.1.1. Physical organization of the bilayer

5.1.2. Biological importance of non-bilayer lipids

5.2. Selectivity of protein–lipid interactions

5.2.1. Lipid association with α-helical proteins

5.2.2. Lipid association with β-barrel proteins

5.2.3. Organization of protein complexes

5.2.4. Supermolecular complex formation

5.2.5. Binding sites for peripheral membrane proteins

5.3. Translocation of proteins across membranes

5.4. Assembly of integral membrane proteins

5.4.1. Lipid-assisted folding of membrane proteins

5.4.2. Molecular determinants of protein topology

5.5. Lipid domains

5.5.1. Lipid rafts

5.5.2. Lipid domains in bacteria

5.6. Cytokinesis

6. Summary and future directions

Abbreviations

References

1 Introduction and overview

Lipids as a class of molecules display a wide diversity in structure and biological function. A primary role of lipids in cellular function is to form the lipid bilayer permeability barrier of cells and organelles (Fig. 1). Glycerophospholipids (termed phospholipids hereafter) are the primary building blocks of membranes but other lipids are important components. Table 1 shows the major lipids found in the membranes of various cells and organelles but does not take into account the minor lipids, many of which are functionally important. Sterols are present in all eukaryotic cells and in a few bacterial membranes. The ceramide-based sphingolipids are also present in the membranes of all eukaryotes. Neutral diacylglycerol glycans are major membrane-forming components in many gram-positive bacteria and in the membranes of plants, while gram-negative bacteria utilize a saccharolipid (Lipid A) as a major structural component of the outer membrane. The variety of hydrophobic domains of lipids results in additional diversity. In eukaryotes and eubacteria, these domains are saturated and unsaturated fatty acids or alkyl alcohols. Archaebacteria contain long-chain reduced poly-isoprene moieties in ether linkage to glycerol instead of fatty acids. If one considers a simple organism such as Escherichia coli with three major phospholipids and several different fatty acids along with many minor precursors and modified products, the number of individual phospholipid species ranges in hundreds. In more complex eukaryotic organisms with greater diversity in both the phospholipids and fatty acids, the number of individual species is in thousands. Sphingolipids also show a similar degree of diversity and when added to the steroids, the size of the eukaryotic lipodome approaches the size of the proteome.

Table 1

Lipid composition of various biological membranes

Lipid	Erythrocyte^a	CHO cells^b	Mitochondria^c		Endoplasmic reticulum^d	E. coli^e
			Outer	Inner
Cholesterol	25	−	N.D.	N.D.	20	N.D.
PE	18	21	33	24	21	75
PC	19	51	46	38	46	N.D.
Sphingomyelin	18	9	−	−	9	N.D.
PS	9	7	1	4	2	<1
PG	0	1	N.D.	N.D.	−	20
CL	0	2.3	6	16	−	5
PI	1	8	10	16	2	N.D.
Glycosphingolipid	10	−	−	−	−	N.D.
PA	−	1	4	2	−	<2

The data are expressed as mole% of total lipid. N.D. indicates not detected and blank indicates not analyzed.

^aHuman [5].

^bChinese hampster cells (T. Ohtsuka, 1993).

^cS. cerevisiae inner and outer mitochondrial membrane (E. Zinser, 1991).

^dMurine L cells (E.J. Murphy, 2000).

^eInner and outer membrane excluding Lipid A (C.R. Raetz, 1990).

Fig. 1 Model for membrane structure. This model of the plasma membrane of a eukaryotic cell is an adaptation of the original model proposed by Singer and Nicholson (S.J. Singer, 1972). The phospholipid bilayer is shown with integral membrane proteins largely containing α-helical transmembrane domains. Peripheral membrane proteins associate either with the lipid surface or with other membrane proteins. Lipid rafts (dark gray head groups) are enriched in cholesterol and contain a phosphatidylinositol glycan-linked (GPI) protein. The light gray head groups depict lipids in close association with protein. The irregular surface and wavy acyl chains denote the fluid nature of the bilayer.

In this chapter, the diversity in structure, chemical properties, and physical properties of lipids will be outlined. The various genetic approaches available to study lipid function in vivo will be summarized. Finally, how the physical and chemical properties of lipids relate to their multiple functions in living systems will be reviewed to provide a molecular basis for the diversity of lipid structures in natural membranes [1].

2 Diversity in lipid structure

Lipids are defined as the biological molecules readily soluble in organic solvents such as chloroform, ether, or toluene. However, many peptides and some very hydrophobic proteins are soluble in chloroform, and lipids with large hydrophilic domains such as saccharolipids are not soluble in these solvents. Here we will consider only those lipids that contribute significantly to membrane structure or have a role in determining protein structure or function. The broad area of lipids as second messengers is covered in Chapters 12–14. The LIPID Metabolites and Pathways Strategy (LIPID MAPS) consortium is identifying, characterizing, and classifying the components of the lipidome and developing a web-based systematic nomenclature for lipids and repository for structural information on lipids. The website of this consortium [2] provides a comprehensive and evolving picture of the lipodome.

2.1 Glycerolipids

The diacylglycerol backbone in eubacteria and eukaryotes is sn-3-glycerol esterified at positions 1 and 2 with long-chain fatty acids (Fig. 2). In archaebacteria (Fig. 3), the opposite isomer sn-1-glycerol forms the lipid backbone and the hydrophobic domain is composed of phytanyl (saturated isoprenyl) groups in ether linkage at positions 2 and 3 (an archaeol) [3]. In addition, two sn-1-glycerol groups are connected in ether linkage by two biphytanyl groups (dibiphytanyldiglycerophosphatetetraether) to form a covalently linked bilayer. Some eubacteria (mainly hyperthermophiles) have dialkyl (long-chain alcohols in ether linkage) phospholipids and similar ether linkages are found in the plasmalogens of eukaryotes. The head groups of the phospholipids (boxed area of Fig. 2) extend the diversity of lipids defining phosphatidic acid (PA, with OH), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylinositol (PI), and cardiolipin (CL). Archaebacteria analogs exist with head groups of glycerol and glyceromethylphosphate as well as all of the above except PC and CL. Archaebacteria, also have neutral glycan lipid derivatives in which mono- and disaccharides (glucose or galactose) are directly linked to sn...

Table of contents

• Cover image
• Title page
• Table of Contents
• Preface
• List of contributors
• Chapter 1: Functional roles of lipids in membranes
• Chapter 2: Lipid modifications of proteins
• Chapter 3: Fatty acid and phospholipid metabolism in prokaryotes
• Chapter 4: Lipid metabolism in plants
• Chapter 5: Oxidation of fatty acids in eukaryotes
• Chapter 6: Fatty acid synthesis in eukaryotes
• Chapter 7: Fatty acid desaturation and chain elongation in mammals
• Chapter 8: Phospholipid biosynthesis in eukaryotes
• Chapter 9: Ether-linked lipids and their bioactive species
• Chapter 10: Lipid metabolism in adipose tissue
• Chapter 11: Phospholipases
• Chapter 12: The eicosanoids
• Chapter 13: Sphingolipids
• Chapter 14: Cholesterol biosynthesis
• Chapter 15: Metabolism and function of bile acids
• Chapter 16: Lipid assembly into cell membranes
• Chapter 17: Lipoprotein structure
• Chapter 18: Assembly and secretion of triacylglycerol-rich lipoproteins
• Chapter 19: Dynamics of lipoprotein transport in the circulatory system
• Chapter 20: Lipoprotein receptors
• Chapter 21: Lipids and atherosclerosis
• Subject index