Impairment of Lipid Metabolism in Ischemic and Reperfused Myocardial Tissue
Samuel Sideman, Rafael Beyar in Analysis and Simulation of the Cardiac System — Ischemia, 2020
With respect to the question about the mechanism underlying the accumulation of NEFA, in particular arachidonic acid, in ischemic tissue, no definitive theory can be offered. At this moment, the most feasible hypothesis is impaired turnover of cellular phosphoglycerides (Figure 2). Enzymes involved in this turnover process are phospholipase A2, hydrolyzing phosphoglycerides into lysophosphoglycerides and NEFA like arachidonic acid. The first step in the resynthesis of phosphoglycerides is accomplished by reesterification of arachidonic acid with CoASH. This step, catalyzed by acylCoA synthetase, is ATP dependent. Arachidonoyl CoA reacts with lysophosphoglyceride to yield a new phosphoglyceride molecule. The latter reaction is catalyzed by lysophosphoglyceride acyltransferase.
Nature, Function, and Biosynthesis of Surfactant Lipids
Jacques R. Bourbon in Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
The problem of a role of lamellar bodies in PC remodeling is more complex. Engle et al.59 found a significant lysoPC-palmitoyltransferase activity in a lamellar body-enriched fraction, somewhat higher than that in the microsomal fraction. Using the same approach as for choline phosphotransferase, Barańska and van Golde233 came to the conclusion that lamellar bodies contain neither lysoPC acyltransferase nor lysoPC:lysoPC acyltransferase. However, intriguingly, they observed a stimulation of microsomal acyltransferase activity by the addition of lamellar bodies. This cooperation may explain the previous observation229 of this activity in lamellar bodies which could not simply be accounted for by microsomal contamination. The authors suggested that the presence of lysosomal-type phospholipases in lamellar bodies141 might explain the cooperative effect. Since these lysosomal-type phospholipases appear to preferentially hydrolyze unsaturated PC,139 participation of lamellar bodies in the enrichment of surfactant with DSPC, even if indirect, cannot be ruled out. An alternative explanation involving a particular remodeling system by direct acyl exchange between palmitoyl-CoA and PC has also been hypothesized.59
Xenobiotic Biotransformation
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
Benzoates and arylacetates are the prototype substrates for characterization of the enzymes catalyzing amino acid conjugation of the carboxylic acid moieties on xenobiotics. Kidney and liver mitochrondria are known sites of localization of the amino acid conjugation enzymes for these substrates. In mammals, there are at least two forms of CoA ligases for benzoic acid as substrate; the two forms are distinguished by differential specificity for salicylate conjugation. There are also at least two N-acyltransferases, one with benzyl CoA as the preferred substrate and one with arylacetyl CoA as the preferred substrate. Additional forms of CoA ligase and N-acyltransferase are specific for bile acid conjugation. Liver microsomes have high activities of these enzymes.
Role of co- and post-translational modifications of SFKs in their kinase activation
Published in Journal of Drug Targeting, 2020
Mei-Lian Cai, Meng-Yan Wang, Cong-Hui Zhang, Jun-Xia Wang, Hong Liu, Hong-Wei He, Wu-Li Zhao, Gui-Ming Xia, Rong-Guang Shao
During palmitoylation, a palmitoyl group (derived from palmitic acid) is post-translationally added to the cysteine, with less added to serine and threonine. This modification is a dynamic and reversible process. Acyltransferases (PATs) mediate the process. Although myristoylation is essential to membrane anchorage of SFKs [32], myristoylation alone is not sufficient for membrane anchorage, and membrane anchorage still requires other modifications such as palmitoylation (in most SFKs) or a polybasic cluster (in Src) to finish collaboratively [41,42], and the effect of palmitoylation as a second signal to membrane anchorage is stronger than the polybasic cluster [43]. Of note, myristoylation is a prerequisite for the palmitoylation of SFKs. With the exception of Src and Blk, all SFKs are palmitoylated at Cys3, Cys5 or Cys6 in the SH4 domain [32,44]. Lyn and Yes are mono-palmitoylated at Cys3, Fyn is dual-palmitoylated at Cys3 and Cys6, and Lck is dual-palmitoylated at Cys3 and Cys5. Palmitoylation at cysteine affects SFKs activity by regulating the trafficking, localisation and stability of SFKs [45,46].
Logistic role of carnitine shuttle system on radiation-induced L-carnitine and acylcarnitines alteration
Published in International Journal of Radiation Biology, 2022
Hai-Xiang Liu, Qing-Jie Liu
CPT2 is anchored from the matrix side on the inner mitochondrial membrane (Figure 2). It reconverts acylcarnitine to acyl-CoA which is the substrate for mitochondrial long-chain FAO. The acyltransferase reaction is reversible, and therefore the net flux through the enzyme will depend on the concentration of substrates and products (Houten et al. 2020). Similar to CACT, CPT2 is not generally considered to play an essential role in transporting long-chain fatty acids to the mitochondrial matrix. Usually, the CPT2 deficiency is observed in patients with specific inborn errors of metabolism. Deficiency of CPT2 in these patients induces the accumulation of long-chain acylcarnitines (C16 and C18), in particular, an elevated (C16 + C18:1)/C2 ratio (Vélot and Srere 2000; Albers et al. 2001; Fingerhut et al. 2001; Al-Sannaa and Cheriyan 2010; Yamada et al. 2017). Both defects of CACT or CPT2 induce the accumulation of long-chain acylcarnitines; whether they relate to radiation-induced accumulation of long-chain acylcarnitines is not yet known.
Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review
Published in Pharmaceutical Biology, 2020
Zhiqin Zhang, Jie Bai, Yawen Zeng, Mengru Cai, Yu Yao, Huimin Wu, Longtai You, Xiaoxv Dong, Jian Ni
Acyl-CoA: cholesterol acyltransferase (ACAT) is responsible for the intracellular esterification of free cholesterol with fatty acyl-CoA to produce cholesterol esters (Chang et al. 2006). An et al. (2007) demonstrated that acetylshikonin was found to weakly suppress human ACAT-1 and ACAT-2, but its analogue propanoylshikonin exerted strong inhibitory effect on ACAT, indicating that the inhibitory potency was associated with the length of the acyl group. In 3T3-L1 cells, acetylshikonin suppressed adipocyte differentiation and the expression of adipogenic transcription factors (PPARγ and C/EBPα) (Gwon et al. 2012). Furthermore, treatment of high fat diet (HFD)-induced obese rats with acetylshikonin led to reductions in body weight, white adipose tissue content, serum triglycerides, and free fatty acid levels. The lipid-regulatory effect was attributed to triacylglycerol hydrolysis via regulation of protein kinase A (PKA) signalling in 3T3-L1 cells (Su et al. 2016a). Acetylshikonin had an excellent therapeutic effect on obesity and non-alcoholic fatty liver disease in spontaneous obese db/db mice. The mechanisms were involved in marked suppression of alanine aminotransferase, aspartate aminotransferase, and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), as well as downregulation of sterol regulatory element-bindingprotein-1 (SREBP-1), fatty acid synthetase (FAS), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (Su et al. 2016b).
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