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Macronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
In humans, fatty acids have a number of physiological roles as: energy substrates, structural and functional components of cell membranes, precursors for lipid mediators, and components affecting signal transduction pathways and gene transcription (70–75). Some fatty acids are not only essential dietary nutrients but also contribute to various physiological processes (74). Certain saturated fatty acids are involved in numerous cellular signaling and stabilization processes in the body. For example, myristic acid, a 14-carbon saturated fatty acid, is a source of myristoyl groups utilized within the body to stabilize many different proteins, including proteins in the immune system, and to fight tumors (74). Myristoleic acid, a metabolite of myristic acid, is known to be cytotoxic to tumor cells such as prostate cancer cells (74). Palmitic acid, a 16-carbon saturated fatty acid, is involved in palmitoylation of protein. This palmitoylated protein formed plays important roles in numerous cellular processes, including signaling, apoptosis, and neuronal transmission, and is used to fight degenerative Huntington’s disease, T-cell mediated immune disorder, and cancer (74). However, excess consumption of palmitic acid, myristic acid, and other saturated fatty acids, increases the risk of developing hypercholesterolemia, cardiovascular disease and cancer.
The Rous Sarcoma Virus Oncogene and its Proto-Oncogene Counterpart
Published in Pimentel Enrique, Oncogenes, 2020
After synthesis, pp605rc forms a complex with two proteins in the cytoplasmic compartment of the cell, and the kinase is thereafter attached to some component of the plasma membrane.86 The pp60src protein is anchored to the plasma membrane by some portion of its amino-terminal domain, whereas the kinase activity is carried by the carboxy-terminal half of the molecule.87 Myristic acid, a rare fatty acid, is attached to the amino terminal region of pp60src of either viral or cellular origin immediately after synthesis and is present in both soluble and membrane bound forms of the protein.88-91 Changes in the amino-terminal sequence of pp60v-src decrease both the membrane association of the protein and its tumorigenic action,92 and a short amino acid sequence (amino acids 2 to 15) within this region is required for pp60src myristylation, membrane association and transformation.88 Changes produced by site-directed mutagenesis techniques in a restricted region of the carboxyl-terminal region of the protein lead to a decrease in the specific kinase activity and also result in a concomitant loss of the transforming potential of the mutant virus.93,94
N-Myristoylation as a Novel Molecular Target for the Design of Chemotherapeutic Drugs
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Ronald L. Felsted, Colin Goddard, Constance J. Glover
Myristoylation of amino terminal glycine is characterized by a very high specificity for myristic acid. If RSV-infected chicken embryo cells are prelabeled with [3H]palmitate, p60src is very weakly radiolabeled compared to cells prelabeled with [3H]myristate.11 Furthermore, when the radioactivity incorporated into the [3H]palmitate-labeled src protein is subsequently analyzed, it is found as myristate rather than as palmitate, presumably originating from metabolism of the longer chain precursor.22 Considering the limited metabolic conversion of fatty acids to their shorter homologs,39 this labeling indicates a remarkable preference for myristic acid. The metabolic labeling of retroviral gag or gag-oncogene hybrid proteins in virus-infected cells has shown a similar preference for myristic acid.15,18,19 This specificity for myristic acid is accentuated by the fact that myristic acid represents <3% of the total fatty acids in mammalian tissues or eukaryotic cells.83,85 In addition, a strict enzymatic specificity for myristoyl CoA over palmitoyl CoA was demonstrated in in vitro kinetic studies with yeast and rat brain N-myristoyl transferases.70,86
Prediction of long-term polysorbate degradation according to short-term degradation kinetics
Published in mAbs, 2023
Sisi Zhang, Caterina Riccardi, Dane Carlson, Douglas Kamen, Kenneth S. Graham, Mohammed Shameem, Hanne Bak, Hui Xiao, Ning Li
PSs are chemically diverse compounds made of ethoxylated sorbitan esterified to a series of fatty acids.32 Regarding the prediction of the earliest time of particle formation due to PS degradation, the release of FFAs other than lauric acid and oleic acid, such as myristic acid and palmitic acid for PS20 degradation, or palmitic acid and stearic acid for PS80 degradation, could also be measured.11,15 In mAb-1 process A, particles first formed because of myristic acid rather than lauric acid precipitation; thus, a prediction based on the myristic acid increase, rather than the lauric acid increase, over the incubation time would provide a more accurate estimate of when particle formation might be expected. The conversion of the incubation time at 37°C over the course of days to 5°C over the course of months was determined on the basis of the myristic acid increase in an accelerated study and stability study (Figure 9a), and the myristic acid increase during the incubation time at 5°C for mAb-1 process B was plotted (Figure 9b). The estimated myristic acid concentration accurately matched the measured value after 24 months (Figure 9c). Given the known myristic acid solubility limit (5.4 µg/mL) at 2–8°C in mAb-1/mAb-2, we would not expect to observe particles due to PS20 degradation within 10 years for mAb-2 despite the detectable lipase activity.
The role of N-myristoyltransferase 1 in tumour development
Published in Annals of Medicine, 2023
Hong Wang, Xin Xu, Jiayi Wang, Yongxia Qiao
Myristoylation is the irreversible covalent bonding of myristic acid (also known as tetradecanoic acid, a 14-carbon saturated fatty acid) to the N-terminal glycine of a protein with myristoyl coenzyme A as the donor [8]. Recent studies have revealed that lysines can also be myristoylated [9]. In eukaryotes, myristoylation occurs in 0.5–3% of the cellular proteome [10]. Although myristoylation affects only a minority of eukaryotic proteins, it is vital for the survival and development of organisms and has implications for various diseases such as cancer [6] and malaria [11]. Myristoylation controls protein function by targeting proteins to specific locations, promoting specific protein–protein and protein–lipid interactions, and causing ligand-induced conformational changes [12]. Familiar myristoylated proteins include the β subunit of calmodulin independent protein phosphatase, the myristoylated alanine-rich C kinase substrate, the α subunit of several G proteins, and several ARF proteins involved in ADP ribosylation [13,14].
A Mediterranean-like fat blend protects against the development of severe colitis in the mucin-2 deficient murine model
Published in Gut Microbes, 2022
Natasha Haskey, Jiayu Ye, Mehrbod Estaki, Andrea A. Verdugo Meza, Jacqueline A. Barnett, Mitra Yousefi, Blake W. Birnie, Samantha Gruenheid, Sanjoy Ghosh, Deanna L. Gibson
Much of the research on diet and IBD has focused on the negative impact of high fat intake and its association with IBD.13,14 However, one diet higher in the recommended fat intake than national guidelines, the Mediterranean diet (MD) (40% by energy derived from fat), has been associated with beneficial effects in immune and metabolic diseases, including IBD.15 Additionally, we and others have shown that the type of fat, independent of caloric content, influence intestinal inflammation, metabolism, and host-microbe function.16,17,18 For example, murine models have demonstrated that n-6 PUFA and saturated fatty acids (SFA) result in inflammation-induced colonic damage while monounsaturated fatty acids (MUFA) are protective. Additionally, the benefits of n-3 PUFA, commonly present in fish oils, may depend on SFA in the diet.17 SFA derived from dairy fat are unique in their compensatory inflammatory responses involved in tissue restitution.16,17 Human observational studies show that after energy-adjustment for total fat intake, myristic acid (a SFA) and long-term intake of trans-fatty acids and n-6 PUFA are associated with an increasing incidence and risk of a flare-up in UC patients.13,14 Understanding the mechanisms of how various fatty acids impact IBD is important in the development of evidence-based guidelines to reduce specific food-induced inflammation, promote remission and dietary tolerance.