“Click Chemistry” for the Simple Determination of Fatty‐Acid Uptake and Degradation: Revising the Role of Fatty‐Acid Transporters

Fatty acids (FAs) have numerous functions in all living organisms, ranging from structural roles and energy production to the biosynthesis of secondary metabolites. Because of the high energy content of exogenous FAs, their acquisition is central of metabolism, and several biological systems are known, although their precise roles are not yet entirely clear. We investigated the roles of FadD (CoA ligase) and FadL (FA transporter) in different bacterial strains by using an improved version of click‐chemistry‐assisted labelling of azido‐FAs. The high sensitivity of this method allows a direct and precise assessment of FA metabolism, and is thus far better suited than growth experiments. Our results show that although FA activation is indeed essential for FA degradation, their transport can be independent of transporters like FadL.     

Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach

Glutamine metabolism has been proved to be dysregulated in many cancer cells, and is essential for proliferation of most cancer cells, which makes glutamine an appealing target for cancer therapy. In order to be well used by cells, glutamine must be transported to cells by specific transporters and converted to glutamate by glutaminase. There are currently several drugs that target glutaminase under development or clinical trials. Also, glutamine metabolism restriction has been proved to be effective in inhibiting tumor growth both in vivo and vitro through inducing apoptosis, growth arrest and/or autophagy. Here, we review recent researches about glutamine metabolism in cancer, and cell death induced by targeting glutamine, and their potential roles in cancer therapy.     

Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long-term cannabis users: A secondary analysis of a case–control study

Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users (n = 21) and non-cannabis users (n = 16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon-specific isotope analysis, which allows for the determination of fatty acid ¹³C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched ¹³C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2-arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti-inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.     

微生物共利用木糖和葡萄糖生产化学品研究进展

木质纤维素生物质是储量丰富的可再生资源,在能源、化工及医药领域具有广阔的应用前景。木质纤维素各组分因氢键和共价键的存在而结合紧密,需经酸、碱、高温、有机溶剂等预处理后才能高效酶解利用,其水解产物的主要成分为己糖（60%～70%,葡萄糖为主）和戊糖（30%～40%,木糖为主）的混合物。本文主要针对水解液中木糖和葡萄糖的共利用效率相关问题,以基因工程改造微生物利用木糖和葡萄糖共发酵生产醇类、生物油脂、γ-聚谷氨酸及有机酸等生物基化学品为主线,从代谢途径重构、基因水平调控及发酵技术优化等方面综述了近年来的研究进展。最后,从菌株筛选、基因与代谢工程调控、细胞固定化、产物处理及发酵工艺等层面总结了该领域目前的研究特点、技术瓶颈和未来的研究方向与思路。     

Dietary n-3 HUFA Affects Mitochondrial Fatty Acid β-Oxidation Capacity and Susceptibility to Oxidative Stress in Atlantic Salmon

Atlantic salmon (Salmo salar) (90 g) were fed four different diets for 21 weeks (final weight 344 g). The levels of n-3 highly unsaturated fatty acids (HUFA) ranged from 11% of the total fatty acids (FA) in the low n-3 diet to 21% in the intermediate n-3 diet, to 55 and 58% in the high n-3 diets. The high n-3 diets were enriched with either docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA). Increasing dietary levels of n-3 HUFA led to increasing percentages (from 31 to 52%) of these FA in liver lipids. The group fed the highest level of DHA had higher expressions of peroxisome proliferator-activated receptor (PPAR) β and the FA β-oxidation genes acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase (CPT)-II, compared to the low n-3 groups. The high n-3 groups had reduced activity of mitochondrial cytochrome c oxidase and β-oxidation capacity, together with increased activities of superoxide dismutase (SOD) and caspase-3 activities. In the group fed the highest level of n-3 HUFA, decreased percentages of major phospholipids (PL) in the mitochondrial and microsomal membranes of the liver were also apparent. The percentage of mitochondrial cardiolipin (Ptd₂Gro) was 3.1 in the highest n-3 group compared to 6.6 in the intermediate group. These data clearly show an increased incidence of oxidative stress in the liver of fish fed the high n-3 diets.     

Detection of a pathway from linoleate to a novel cyclopentenone: cis-12-oxo-10-phytoenoic acid in sunflower roots

The lipoxygenase pathway in sunflower roots was studied in vitro. A preliminary incubation of linoleic acid with 15 000 g supernatant of homogenate of sunflower roots (1.5-6 days after germination) revealed the predominant activity of 13-lipoxygenase. The exogenously added linoleic acid 13-hydroperoxide is further utilized through two competing pathways. One of them is directed towards formation of the ketodiene (9Z,11E)-13-oxooctadeca-9,11-dienoic acid. The second pathway, which is controlled by allene oxide synthase, leads to the formation of an alpha-ketol and a novel cyclopentenone, rac-cis-12-oxo-10-phytoenoic acid (12-oxo-PEA) via a short-lived allene oxide. Unexpectedly, the cyclopentenone 12-oxo-PEA is the predominant allene oxide synthase product. Identification of cis-12-oxo-PEA was confirmed by its UV, mass, (1)H NMR and 2D-COSY spectral data. The highest yield of 12-oxo-PEA is observed in very young roots (1.5-2 days after germination). The results of methanol-trapping experiments demonstrate that both 12-oxo-PEA and alpha-ketol are formed through the unstable allene oxide intermediate, (9Z)-12,13-epoxyoctadeca-9,11-dienoic acid, which is the primary product of allene oxide synthase. Since 12-oxo-PEA is a jasmonate congener, its biosynthesis in plants might be of physiological importance.     

水溶剂法合成葡萄糖脂肪酸酯

对水溶剂法合成葡萄糖脂肪酸酯的工艺作了正交设计实验,优选出水溶剂法合成葡萄糖脂肪酸酯的工艺参数为:n(葡萄糖)∶n(脂肪酸甲酯)=1.5∶1,乳化剂用量15%,催化剂用量2%,反应温度120℃,反应时间为2h。用此工艺参数可获得产率大于80%,单酯含量50%以上的葡萄糖脂肪酸酯的产品。     

Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3–17. Analysis of the fatty acid composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (p < 0.001). In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the autistic participants (n = 20) compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism.     

Development and application of a fluoride-detection-based fluorescence assay for γ-butyrobetaine hydroxylase

Fluoride assays for oxygenases: The 2-oxoglutarate-dependent oxygenase BBOX catalyses the final step in carnitine biosynthesis and is a medicinal chemistry target. We report that BBOX can hydroxylate fluorinated substrates analogues with subsequent release of a fluoride ion, thereby enabling an efficient fluorescence-based assay.