Handbook of Lipid Research – serie

The early history and development of the field of glycolipids was concerned mainly with the predominant glycolipids found in higher animal tissues, namely the glycosphingolipids, as has been extensively documented by J. N. Kanfer and S. Hakomori in Volume 3 of this series. The major glycolipids in organisms of the plant kingdom, however, such as bacteria, yeasts and fungi, algae, and higher plants, are glycoglycerolipids, although glycosphingolipids are also present as minor components in these organisms, except for bacteria. It is of interest that one of the pioneers in glycosphingolipid research, Herbert E. Carter, also pioneered the discovery and structural elucidation of the plant galactosyldiacylglycerols. This class of glycolipids is present in chlo­ roplast membranes and must surely be one of the most ubiquitous and abun­ dant natural substances in the world, thereby deserving the attention of lipid biochemists. It is therefore surprising to learn that in contrast to the glycosphingolipids, which were discovered in the 1870s, glycoglycerolipids were not discovered until the 1950s. Since that time investigations of the structure and distribution of these glycolipids have proceeded at an exponen­ tially increasing rate, and much information is now available for representa­ tives of many genera of bacteria, yeasts, algae, and higher plants. Glycoglyce­ rolipids have also been identified in animal cells, particularly in the brain, testes, and sperm.

This book examines closely the structure of various lipids through specific examples of mass spectral data obtained by different ionization techniques-including electron ionization, chemical ionization, and fast atom bombardment. Including over 80 complete mass spectra of lipids as well as over 120 detailed mechanistic schemes of their ion chemistry, this work will provide the advanced student and experienced mass spectroscopist with a fundamental base of information on fatty acyl-type lipids.

Lipids traditionally have been viewed as serving two functions: to form cellular membranes and to serve as energy stores. During the last two decades, a new role for lipids has taken center stage: lipids can act as signalling molecules. This book deals with a variety of lipids that have been shown to be messengers. Leading scientists explore all known lipid classes except steroid hormones. Researchers and educators in biochemistry as well as in molecular and cellular biology will appreciate this volume.

The first demonstration of the existence of a vitamin and the full recognition of this fact are often attributed to the work of McCollum, who found that a sub­ stance in butterfat and cod-liver oil was necessary for growth and health of ani­ mals fed purified diets. It became obvious that an organic substance present in microconcentrations was vital to growth and reproduction of animals. Following the coining of the word vitamine by Funk, McCollum named this fat-soluble sub­ stance vitamin A. We can, therefore, state that vitamin A was certainly one of the first known vitamins, yet its function and the function of the other fat-soluble vitamins had remained largely unknown until recent years. However, there has been an explosion of investigation and new information in this field, which had remained quiescent for at least two or three decades. It is now obvious that the fat-soluble vitamins function quite differently from their water-soluble counter­ parts. We have learned that vitamin D functions by virtue of its being converted in the kidney to a hormone that functions to regulate calcium and phosphorus metabolism. This new endocrine system is in the process of being elucidated in detail, and in addition, the medical use of these hormonal forms of vitamin D in the treatment of a variety of metabolic bone diseases has excited the medical com­ munity.

The advances in lipid biochemistry over the past 25 to 30 years have been dramatic and exciting. The elucidation of the pathways of fatty acid biosynthesis and oxidation, the delineation of the biogenesis of cholesterol from small-molecular­ weight precursors, the structure proof of simple and complex lipids from plants, animals, and microorganisms, are excellent examples of the spectacular advances made during the golden era of lipid biochemistry. The multifaceted discoveries in these diverse areas of study could be attributed to development of highly sophisticated column chromatographic techniques for separation and purification of simple and complex lipids. The advent of thin-layer chromatography as well as gas­ liquid chromatography provided an explosive impetus to research developments in this field. Concomitant advances in mass spectrometry allowed an interface with gas-liquid chromatography which spawned even greater insight into the structure of lipids. These eventful days of lipid chemistry nearly 25 years ago led to a relatively quiescent period wherein scientists applied these newly available techniques to investigation of the behavior of isolated (lipid) enzyme systems and to unraveling the intricacies of the metabolic behavior of lipids in the intact cell or whole organisms. Then, in the early 1960s, a decided change in research emphasis developed with the advent of a simple, reproducible procedure for the isolation of cell membranes.

Phospholipases are a class of ubiquitous enzymes that have in common their substrate and the fact that they are all esterases. Beyond that, they are a diverse group of enzymes that fall into two broad categories, the acyl hydro- lases and the phosphodiesterases. The former group is made up of the phos- pholipases Al and A , phospholipase B, and the lysophospholipases. On the 2 other hand, the phosphodiesterases are the phospholipases C and D. The scheme indicates the site of attack of each type of phospholipase. PLA 1 PLB~j ft 0\ ~-C-O-C-R d ~ 2 I 1 R-C-0-C-H 0 2 /H2-6-0-U-0-x PLA, ~ 6- '" PLC PLD The lysophospholipases, not shown, have in some cases properties similar to phospholipase B and are known to attack the acyl ester at either position 1 or position 2 of the glycerol backbone. Furthermore, some of the phos- pholipases C and D do not hydrolyze phosphoglycerides but use sphingo- myelinase as their substrate. These phospholipases C are also referred to as sphingomyelinases. The products of that reaction are phosphocholine plus ceramide.

Interest in and emphasis upon different aspects of the sphingolipids have, in general, followed the biochemical developments of the day. The early inves- tigators were preoccupied principally with the isolation of "pure" compounds and structural elucidation. This historical perspective is found in the discus- sion presented in Chapter 1 (Section 1. 1. 2 and Table III). Still, the isolation and structural characterization of glycolipids are the basic foundation of all our knowledge of enzymology, immunology, and cell biology. Recent infor- mation obtained on structure has greatly affected the interpretation of various phenomena related to glycolipids. New structures suggest a new role of gly- colipids as antigens and receptors. Ten years ago, only four neutral glycolipids and two gangliosides were known in human erythrocytes. We now know structures of at least twenty additional neutral glycolipids and ten additional gangliosides in human erythrocytes that are known to be important blood group, heterophil, and autoantigens. Erythrocytes are only one example of a cell type whose glycolipid profile has been extensively studied.Our defective knowledge in immunology and cell biology may be due to incomplete un- derstanding of structural chemistry. Modern methodology based on methyla- tion analysis, mass spectrometry, and enzymatic degradation has supple- mented classical analysis based on clorimetry. Nuclear magnetic resonance spectroscopy is still in the development stage, but will eventually replace var- ious chemical analyses. However, important future studies should be directed toward elucidating the organizational structure of glycolipids in membranes.

Lipids traditionally have been viewed as serving two functions: to form cellular membranes and to serve as energy stores. During the last two decades, a new role for lipids has taken center stage: lipids can act as signalling molecules. Leading scientists explore all known lipid classes except steroid hormones.