Academic literature on the topic 'Choline-containing phospholipids'

This book provides a concise introduction to phospholipid chemistry and is intended for a broad audience of biologists, biochemists, and graduate students. Developed as part of a graduate course on lipids, this book also serves as a reference for laboratory investigators on signal transduction and biological membranes. The first part of the text is devoted to an orientation to the chemical nature of lipids in general, how they are thought to be associated in the cell, and the methodology by which the cellular lipids (including the phospholipids) can be recovered from cells and subjected to an

In choosing the order for discussion of phospholipids, it is not the intention to single out one particular group as the most important; rather, an initial premise would be that all phospholipids are critical to a cell’s structure and metabolism. Certainly, as has been emphasized before, phospholipids have been shown to have key roles in the process of cellular signal transduction, and it is debatable which of several types of phospholipids is the most important. There is no doubt that the mechanism of involvement of membrane phospholipids in these complex reactions has presented a major experimental challenge, and as such this has titillated the acute scientific senses of many researchers. It is equally true also that an important field of study is emerging in cell signaling, in which unusual cellular disorders have been noted. Certainly the latter will implicate alterations or aberrations in membrane phospholipid chemistry and metabolism in one way or another. This digression was made to show quite simply that it behooves one to understand the chemical/ biochemical characteristics of the phospholipids in order to best meet the challenges of this field (and, of course, other related ones as well). On the basis of undoubted faulty logic on the choice of the order of topics, one simply can retreat to the argument of personal preference. Thus, the first group of compounds will be the choline-containing phospholipids—that is, the choline phosphoglycerides and the choline sphingolipids. As it so happens, these are among the most ubiquitous phospholipids in nature and, at least in the early “chemical” years of investigations on the phospholipids, the best-studied group. It is assumed at this junction that a highly purified phospholipid has been obtained, usually through the use of chromatographic procedures. A frequently asked question is, How do I tell whether the sample is pure? It is a logical question, especially with compounds isolated from naturally occurring sources. In actual fact, there is no simple answer.

The diversity of phospholipids present in the mammalian cell membranes continues to titillate one’s scientific senses. In addition to the presence of at least 12 different structural types of phospholipids in a cell that serve to complicate the picture, there are species within species. If one considers the diacyl, alkylacyl, and alkenylacyl variants, plus the number of different fatty acyl and fatty ether combinations, there can be several hundred different species present. Certainly progress is being made in relating certain species with a particular cellular process, and this is no doubt an exciting and important area of study. However, this is only the tip of the “cellular iceberg,” since there is little or no information on the biological role of the majority (certainly over 75%) of the phospholipids. Questions to be asked center on the need for such a spectrum of phospholipids. Are some structural components only, are some vestigial remnants, or do they play a crucial role in biological reactions yet to be discovered? There is no simple answer as yet, but this trend of thought should be kept in mind in any investigation on membrane lipid behavior. An important route to interpreting the role of various phospholipids in a biological milieu is to be certain of the chemical structure and identification of the molecules under study. So in continuation of the general format used in Chapter 4, the chemistry of the ethanolamine-, inositol-, and serine-containing phosphoglycerides will be explored at this point. A limited excursion will be made as to their participation in biological reactions. Though the above three classes of compounds share certain common structural features, there are sufficient differences to warrant separate treatment of each group of compounds. For example, the ethanolamine-containing phosphoglycerides can contain, in addition to the diacyl form, an alkylacyl and/or alkenylacyl form. Inositol-containing phosphoglycerides other than the diacyl type have not been reported, but several other phosphorylated species have been detected. The serine-containing phosphoglycerides have been found only as diacyl derivatives.

The neurological complications of AIDS (neuro AIDS) represent the principal cause of disability and death in HIV-patients (Gray et al., 1993; McArthur, et al., 1993). Several types of lesions affect the brain tissue: direct infection of the nervous tissue by HIV, opportunistic infections (such as toxoplasmosis, cytomegalovirus encephalitis, tuberculosis, progressive rnultifocal encephalopathy....), and lymphomas. The AIDS-related dementia complex (ADC) affects about 60% of patients in the late stage of AIDS. ADC is characterized by the occurrence of sub-cortical dementia with cognitive, behavioral, and motor decline, psychomotor slowing and apathy. ADC is related to the presence of a diffuse encephalopathy leading to a cortical and sub-cortical atrophy, as well as diffuse white-matter lesions. There is a distinct advantage in diagnosing as early as possible the neurological complications (e.g. encephalopathy) of AIDS, since early treatment can improve significantly the quality of life in patients by slowing down or even stopping the neurological and psychological degradation. Neuroimaging techniques, and mainly magnetic resonance imaging (MRI), constitute so far the best diagnostic tools of neuro-AIDS (Kent et al., 1993; Mundinger et al., 1992). In addition, localized magnetic resonance spectroscopy (MRS) of the brain provides a non-invasive exploration of intracerebral metabolism in vivo, and can be performed following a standard MRI examination [for a review see Vion-Dury et al. (1994)]. Several key molecules of brain metabolism can be detected, including N-acetyl-aspartic acid which is thought to be a neuronal marker, choline-containing molecules (involved in phospholipid metabolism), glutamate, glutamine, inositol, phosphocreatine and creatine, and lactate. Recently, significant modifications in the concentration of brain metabolites detected by phosphorus and proton MRS have been described in patients with ADC (Bottomley et al., 1992; Deicken et al., 1991; Menon et al., 1992; Chong et al., 1993; Meyerhoff et al., 1993; Confort-Gouny et al., 1993). In a preliminary study, we have observed that even, if MR images are normal (without atrophy, focal or diffuse lesions) or if the patients are neuroasymptomatic, the values of metabolic parameters measured by MRS are often modified (Vion-Dury et al., 1994).