A H Merrill

A special category of phospholipase D (PLD) in the venom of the brown recluse spider (Loxosceles reclusa) and several other sicariid spiders accounts for the dermonecrosis and many of the other clinical symptoms of envenomation. Related proteins are produced by other organisms, including fungi and bacteria. These PLDs are often referred to as sphingomyelinase Ds (SMase Ds) because they cleave sphingomyelin (SM) to choline and “ceramide phosphate.” The lipid product has actually been found to be a novel sphingolipid: ceramide 1,3-cyclic phosphate (Cer1,3P). Since there are no effective treatments for the injury induced by the bites of these spiders, SMase D/PLDs are attractive targets for therapeutic intervention, and some of their features will be described in this minireview. In addition, two simple methods are described for detecting the characteristic SMase D activity using a fluorescent SM analog, (N …

Donald Bruce McCormick, PhD, Professor Emeritus of Biochemistry, Emory University, died on April 21, 2022, at age 89. Don was a prototypic “nutritional biochemist,” as he discussed in “On Becoming a Nutritional Biochemist”[1] and an associated interview [2]. His publications spanned 64 years and were major contributions to knowledge about riboflavin (vitamin B-2), vitamin B-6, biotin, and lipoic acid, and to dietary guidelines and other aspects of nutrition as well as metal ion biochemistry, photochemistry, microbiology, and drug delivery [3]. Don was equally productive in teaching and service [1], which included a term as President of the American Society for Nutrition (ASN) in 1991.

Lipids are historically considered a source of energy and a component of cell membranes. Over the last years, many other functions have been studied, and their importance in our health is well established. For this reason, studies on lipidomics have been increasing in the clinical and food science areas. In this chapter, the basic concepts of lipidomics are introduced and the classical workflow is explained. Additionally, several application examples are present to demonstrate the importance of lipidomics.

Glycolipids encompass a wide variety of compounds that contain both glycans (i.e., carbohydrates) and lipids. The type of lipid moiety and attached carbohydrate(s) determine the categories and subcategories, which include: fatty acyl glycolipids, glycosphingolipids (cerebrosides, globosides, gangliosides, sulfatides and others), glycoglycerolipids, glycophospholipids (e.g., phosphatidylinositols), glycosylated prenols (e.g., dolichol-phospho-glycans), glycosylated sterols, glycosylated polyketides and saccharolipids. This review provides a brief overview of the types of functions these compounds perform, the structural features of the different categories, and a few examples of how structural diversity is achieved. Although the “glycolipidolome” is formidably large, it is becoming more assessable to characterization as the tools of the “omics” revolution expand to include mass spectrometry and other techniques for …

Gaucher disease (GD) is currently the focus of considerable attention due primarily to the association between the gene that causes GD (GBA) and Parkinson’s disease. Mouse models exist for the systemic (type 1) and for the acute neuronopathic forms (type 2) of GD. Here we report the generation of a mouse that phenotypically models chronic neuronopathic type 3 GD. Gba-/-;Gbatg mice, which contain a Gba transgene regulated by doxycycline, accumulate moderate levels of the offending substrate in GD, glucosylceramide, and live for up to 10 months, i.e. significantly longer than mice which model type 2 GD. Gba-/-;Gbatg mice display behavioral abnormalities at ∼4 months, which deteriorate with age, along with significant neuropathology including loss of Purkinje neurons. Gene expression is altered in the brain and in isolated microglia, although the changes in gene expression are less extensive than in mice …

Since inhibitors of sphingosine kinases (SK1, SK2) have been shown to induce p53-mediated cell death, we have further investigated their role in regulating p53, stress activated protein kinases and XBP-1s in HEK293T cells. Treatment of these cells with the sphingosine kinase inhibitor, SKi, which fails to induce apoptosis, promoted the conversion of p53 into two proteins with molecular masses of 63 and 90 kDa, and which was enhanced by over-expression of ubiquitin. The SKi induced conversion of p53 to p63/p90 was also enhanced by siRNA knockdown of SK1, but not SK2 or dihydroceramide desaturase (Degs1), suggesting that SK1 is a negative regulator of this process. In contrast, another sphingosine kinase inhibitor, ABC294640 only very weakly stimulated formation of p63/p90 and induced apoptosis of HEK293T cells. We have previously shown that SKi promotes the polyubiquitination of Degs1, and …

Riboflavin is a B-vitamin, also known as vitamin B2, and is an essential component of the diets of humans and higher animals. Conversion to its coenzyme derivatives: flavin mononucleotide or riboflavin phosphate (FMN) and flavin adenine dinucleotide (FAD) enables it to participate in many essential enzyme-catalyzed reactions involving electron transfer, that is, oxidation and reduction reactions. Human riboflavin deficiency is fairly common in developing countries, especially where food sources derived from meat or dairy products are lacking, but it is rarely life threatening. Interactions with other nutrients, diseases, and medicines are wide ranging and potentially important.

A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for …