The effect of methylated phosphatidylethanolamine derivatives on the ionization properties of signaling phosphatidic acid

Kwarteng, Desmond Owusu; Gangoda, Mahinda; Kooijman, Edgar E.

doi:10.1016/j.bpc.2023.107005

Cited by 2 publications

(2 citation statements)

References 231 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dimethyl phosphatidyl ethanolamine interacts with signaling proteins, modulating their activity and influencing various cellular processes, including cell growth, differentiation, and apoptosis. It also regulates the trafficking of proteins and lipids within the cell, which is crucial for cell signaling, protein sorting, and organelle biogenesis [36,37]. Decreased levels of this phospholipid are observed in the brains of Alzheimer's disease and Parkinson's disease patients, suggesting its potential involvement in the pathogenesis of these neurodegenerative disorders [38,39].…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer

Benabdelkamel,

Jaber,

Akkour

et al. 2024

Metabolites

View full text Add to dashboard Cite

Uterine cancer is the most prevalent gynecologic malignancy in women worldwide. Endometrial cancer (EC) has an 81% five-year survival rate, depending on disease stage and time of diagnosis. While endometrial cancer is largely treatable when detected early, no established screening techniques are available in clinical practice. As a result, one of the most significant issues in the medical field is the development of novel ways for early cancer identification, which could boost treatment success rates. Liquid chromatography–high-resolution mass spectrometry (LC-HRMS)-based metabolomics was employed to explore the metabolomic markers and pathways unique to this cancer type and link them to the benign endometrial hyperplasia that may progress to cancer in 5% to 25% of patients. The study involved 59 postmenopausal participants, 20 with EC type 1, 20 with benign hyperplasia, and 19 healthy participants. Metabolite distribution changes were analyzed, and 338 of these features were dysregulated and significant. The first two main components, PC1 and PC2, were responsible for 11.5% and 12.2% of the total metabolites, respectively. Compared with the control group (CO), EC samples had 203 differentially expressed metabolites (180 upregulated and 23 downregulated); in hyperplasia (HP), 157 metabolites were dysregulated (127 upregulated and 30 downregulated) compared to the CO group while 21 metabolites exhibited differential regulation (16 upregulated and 5 downregulated) in EC plasma samples compared to the HP group. Hyperplasia samples exhibited similar metabolic changes to those reported in cancer, except for alterations in triglyceride levels, 7a,12 b-dihydroxy-5b-Cholan-24-oic acid, and Hept-2-enedioyl carnitine levels. The metabolites N-heptanoyl glycine and -(Methylthio)-2,3-isopentyl phosphate and formimino glutamic acid can be specific markers for hyperplasia conditions and dimethyl phosphatidyl ethanolamine and 8-isoprostaglandin E2 can be specific markers for EC conditions. Metabolic activities rely on mitochondrial oxidative phosphorylation for energy generation. The changes in metabolites identified in our study indicate that endometrial cancer cells adopt alternative strategies to increase energy production to meet the energy demand, thereby supporting proliferation.

show abstract

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer

Benabdelkamel,

Jaber,

Akkour

et al. 2024

Metabolites

View full text Add to dashboard Cite

show abstract

“…17 In addition, PA lipids exhibit an electrostatic-hydrogen bond switch that leads to deprotonation and an increase in the headroup charge. 2,[18][19][20][21] Since the pKa 2 value of PA is close to the physiological pH of cells (6.6-7.9), 2,19,[22][23][24][25] there is a high likelihood of finding a PA lipid with À2 charge. In addition, the presence of multiple positively charged residues further lowers the pKa 2 value of PA lipids.…”

Section: Introductionmentioning

confidence: 99%