China
Africa
Explore chapters and articles related to this topic
Nature, Function, and Biosynthesis of Surfactant Lipids
Published in Jacques R. Bourbon, Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
Two pathways exist in animal cells for the de novo production of PC. The first, called the CDP-choline pathway, consists of the incorporation of choline activated as CDP-choline in a 1,2-diacylglycerol. In the second, called the methylation pathway, PE is similarly generated from CDP-ethanolamine and diglyceride and subsequently undergoes three successive methylations, with S-adenosyl methionine serving as the methyl donor, to form PC. Misidentification of phosphatidyldimethylethanolamine on thin-layer chromatography at one time led to a postulate of major importance of the methylation pathway in fetal lung.108 It was soon established and is now generally accepted that the CDP-choline pathway is, in fact, the primary mechanism for PC synthesis in the lung.109,110
Purification and Primary Culture of Type II Pneumocytes and Their Application in the Study of Pulmonary Metabolism
Published in Joan Gil, Models of Lung Disease, 2020
From available reports, it appears that type II cells prefer glucose, acetate, and palmitate as substrates for the synthesis of surfactant phospholipids (Kikkawa et al., 1975; Batenburg et al., 1978; Smith and Kikkawa, 1979). From studies of isolated type II cells, evidence has accumulated indicating that the CDP-choline pathway is the major, if not the only, route for the de novo synthesis of phosphatidyl choline. Experiments with isolated type II cells indicate that dipalmitoylphosphatidyl choline can be produced directly by the CDP-choline pathway (Smith and Kikkawa, 1978; Post et al., 1983). However, a significant portion of dipalmitoylphosphatidyl choline is probably produced by a remodeling mechanism (Smith and Kikkawa, 1978). The major mechanisms that have been proposed for this remodeling process are a deacylation-reacylation cycle catalyzed by phospholipase A2 and lysophosphatidyl choline acyltransferase, respectively; and a deacylation-transacylation process involving the sequential action of phospholipase A2 and lysophosphatidyl-choline/lysophosphatidyl choline acyltransferase (Batenburg and Van Golde, 1979). In both adult and fetal type II cells the conversion of the intermediate l-palmitoyl-sn-glycerol-3-phosphocholine proceeds by reacylation rather than by transacylation (Batenburg et al., 1979). Studies with type II cells isolated from adult and fetal rat lung (Post et al., 1984; Van Golde et al., 1985) led to the conclusion that choline phosphate cytidyltransferase catalyses an important regulatory step in the formation of surfactant phosphatidylcholine. Moreover, a ratio of 8:1 is seen for dipalmitoylphosphatidyl choline and phosphatidyl glycerol in both type II cell and lung lavage, which suggests that the type II cell is the only source for pulmonary surfactant lipids (Kikkawa and Smith, 1983).
Molecular and Functional MR Imaging of Cancer
Published in Michel M. J. Modo, Jeff W. M. Bulte, Molecular and Cellular MR Imaging, 2007
Michael A. Jacobs, Kristine Glunde, Barjor Gimi, Arvind P. Pathak, Ellen Ackerstaff, Dmitri Artemov, Zaver M. Bhujwalla
Choline phospholipid metabolism comprises a complex network of biosynthetic and breakdown pathways, with one or more enzymes acting per pathway. Choline kinase generates intracellular PC in the cytosine diphosphate choline (CDP choline) pathway, the major biosynthetic pathway for de novo phosphatidylcholine (PtdCho) synthesis in mammalian cells. PtdCho-specific phospholipase C produces PC from membrane PtdCho by a breakdown pathway. Cytosine triphosphate (CTP):phosphocholine cytidylyltransferase utilizes PC, and therefore its activity correlates inversely with intracellular PC levels. PC itself has been reported to be mitogenic and may be a second messenger or mediator for the mitogenic activity of several growth factors.82,83 Recent studies have started exploring the possibility of altering the expression or activity of enzymes involved in choline phospholipid metabolism as novel therapeutic targets for cancer treatment. Since phosphatidylcholine-specific phospholipase D (PC-PLD) was shown to be involved in many aspects of cell proliferation and oncogenic signaling, it could prove valuable as a target for therapeutic intervention in cancers, particularly breast cancers.84–87 Overexpression of choline kinase has been reported in several human tumor-derived cell lines of multiple origins, as well as biopsies of lung, colon, and prostate carcinomas, which were compared to matching normal tissue from the same patient.88 The activity of choline kinase was shown to be higher in malignant tissue.89–91Figure 8.11a shows an example of this increase in choline kinase expression levels in malignant breast cancer cell lines compared to a nonmalignant human mammary epithelial cell line. Ras oncogene transformation has also been linked to choline kinase stimulation in cancers leading to elevated PC levels.79,92–94 Ras GTPases are among the most important oncogenes in human carcinogenesis, and roughly 30% of all human tumors contain ras mutations.95 Choline kinase inhibition96–98 and downregulation by means of small interfering RNA (siRNA)99 are currently being investigated as potential novel antitumor therapies. Downregulation of choline kinase in human breast cancer cells using siRNA specific to choline kinase was found to efficiently decrease cellular 1H MR-detectable PC levels, while human mammary epithelial cells remained unaffected by this treatment,99 as demonstrated in Figure 8.11. The emerging knowledge of the genetic and molecular regulation of choline kinase, as well as other enzymes in the choline phospholipid metabolic pathway, will have a significant impact on improving potential choline kinase-targeted cancer therapies and on identifying other potential targets in the choline cycle. Noninvasive MRS and MRSI of choline phospholipid metabolites will prove valuable in future studies to evaluate these novel therapies.
Choline: The Neurocognitive Essential Nutrient of Interest to Obstetricians and Gynecologists
Published in Journal of Dietary Supplements, 2020
Taylor C. Wallace, Jan Krzysztof Blusztajn, Marie A. Caudill, Kevin C. Klatt, Steven H. Zeisel
Nutrient needs vary depending upon a number of modifiable and nonmodifiable factors; current DRIs for nutrients consider the impact of sex, age, and reproductive life stage on nutrient needs. However, additional variation in nutrient needs still remains, and many researchers hypothesize that genetic variants contribute to this variation. For dietary choline, a large and growing body of research has supported the notion that common genetic variants in genes required for choline, folate, and one-carbon metabolism influence dietary choline requirements. Several single nucleotide polymorphisms (SNPs) have been shown to predict the likelihood of developing signs of choline deficiency in controlled laboratory settings where dietary choline intake is low, as recently reviewed by Ganz, Cohen et al. (2017) and Ganz, Klatt et al. (2017) (Table 2). These variants also impact the metabolic fate of choline, influencing the relative amount of choline that is used to make phosphatidylcholine through the CDP-choline pathway or oxidized to the methyl donor, betaine.