Nature Communications
·
2020
·Vol. 11
·期 1
·1-11
·
IF 12.121
Cao Wenbo,Cheng Simin,Yang Jing,Feng Jiaxin,Zhang Wenpeng,Li Zishuai,Chen Qinhua,Xia Yu,Ouyang Zheng,Ma Xiaoxiao
Lipids play a pivotal role in biological processes and lipid analysis by mass spectrometry (MS) has significantly advanced lipidomic studies. While the structure specificity of lipid analysis proves to be critical for studying the biological functions of lipids, current mainstream methods for large-scale lipid analysis can only identify the lipid classes and fatty acyl chains, leaving the C=C location and sn -position unidentified. In this study, combining photochemistry and tandem MS we develop a simple but effective workflow to enable large-scale and near-complete lipid structure characterization with a powerful capability of identifying C=C location(s) and sn -position(s) simultaneously. Quantitation of lipid structure isomers at multiple levels of specificity is achieved and different subtypes of human breast cancer cells are successfully discriminated. Remarkably, human lung cancer tissues can only be distinguished from adjacent normal tissues using quantitative results of both lipid C=C location and sn -position isomers.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Yongjian Wen,Yuying Li,Tingting Liu,Lijia Huang,Linbo Yao,Dan Deng,Wenjuan Luo,Wenhao Cai,Shaoqi Zhong,Tao Jin,Xinmin Yang,Qiqi Wang,Wen Wang,Jing Xue,Rajarshi Mukherjee,Jiwon Hong,Anthony R. Phillips,John A. Windsor,Robert Sutton,Fei Li,Xin Sun,Wei Huang,Qing Xia
Background The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing globally and more so in China. The characteristics of liver-mediated metabolites and related key enzymes are rarely reported in HTG-AP. Chaiqin chengqi decoction (CQCQD) has been shown to protect against AP including HTG-AP in both patients and rodent models, but the underlying mechanisms in HTG-AP remain unexplored. Purpose To assess the characteristics of liver-mediated metabolism and the therapeutic mechanisms of CQCQD in HTG-AP. Methods Male human apolipoprotein C3 transgenic (h ApoC3 -Tg; leading to HTG) mice or wild-type littermates received 7 intraperitoneal injections of cerulein (100 μg/kg) to establish HTG-AP and CER-AP, respectively. In HTG-AP, some mice received CQCQD (5.5 g/kg) gavage at 1, 5 or 9 h after disease induction. AP severity and related liver injury were determined by serological and histological parameters; and underlying mechanisms were identified by lipidomics and molecular biology. Molecular docking was used to identify key interactions between CQCQD compounds and metabolic enzymes, and subsequently validated in vitro in hepatocytes. Results HTG-AP was associated with increased disease severity indices including augmented liver injury compared to CER-AP. CQCQD treatment reduced severity and liver injury of HTG-AP. Glycerophospholipid (GPL) metabolism was the most disturbed pathway in HTG-AP in comparison to HTG alone. In HTG-AP, the mRNA level of GPL enzymes involved in phosphocholine (PC) and phosphatidylethanolamine (PE) synthesis ( Pcyt1a, Pcyt2, Pemt, and Lpcat ) were markedly upregulated in the liver. Of the GPL metabolites, lysophosphatidylethanolamine LPE(16:0) in serum of HTG-AP was significantly elevated and positively correlated with the pancreas histopathology score ( r = 0.65). In vitro, supernatant from Pcyt2 -overexpressing hepatocytes co-incubated with LPE(16:0) or phospholipase A2 (a PC- and PE-hydrolyzing enzyme) alone induced pancreatic acinar cell death. CQCQD treatment downregulated PCYT1a and PCYT2 enzyme levels in the liver. Hesperidin and narirutin were identified top two CQCQD compounds with highest affinity docking to PCYT1a and PCYT2. Both hesperidin and narirutin reduced the level of some GPL metabolites in hepatocytes. Conclusion Liver-mediated GPL metabolism is excessively activated in HTG-AP with serum LPE(16:0) level correlating with disease severity. CQCQD reduces HTG-AP severity partially via modulating key enzymes in GPL metabolism pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-18
·
IF 14.7
Xu Shuling,Zhu Zhijun,Delafield Daniel G.,Rigby Michael J.,Lu Gaoyuan,Braun Megan,Puglielli Luigi,Li Lingjun
Dysregulated glycerophospholipid (GP) metabolism in the brain is associated with the progression of neurodegenerative diseases including Alzheimer’s disease (AD). Routine liquid chromatography-mass spectrometry (LC-MS)-based large-scale lipidomic methods often fail to elucidate subtle yet important structural features such as sn -position, hindering the precise interrogation of GP molecules. Leveraging high-resolution demultiplexing (HRdm) ion mobility spectrometry (IMS), we develop a four-dimensional (4D) lipidomic strategy to resolve GP sn -position isomers. We further construct a comprehensive experimental 4D GP database of 498 GPs identified from the mouse brain and an in-depth extended 4D library of 2500 GPs predicted by machine learning, enabling automated profiling of GPs with detailed acyl chain sn -position assignment. Analyzing three mouse brain regions (hippocampus, cerebellum, and cortex), we successfully identify a total of 592 GPs including 130 pairs of sn -position isomers. Further temporal GPs analysis in the three functional brain regions illustrates their metabolic alterations in AD progression.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIORESOURCE TECHNOLOGY
·
2025
·
IF 9
Jihang Zhang,Siwen Ji,Jinming Zhang,Yihui Luo,Yanjun Chen,Jinglan Wu,Pengpeng Yang,Fengxia Zou,Hanjie Ying,Wei Zhuang
Lipase conformational dynamics at carrier interfaces dictate biocatalytic performance, yet their structural adaptability and molecular underpinnings remain unclear. This study elucidates how reduced graphene oxide (rGO) surface hydrophobicity modulates lipase activation through spectroscopy and molecular dynamics simulations, unveiling enzyme-specific mechanisms. By tuning rGO reduction, we found that rGO-4 h optimally enhanced Candida antarctica lipase B (CALB) activity by 201.4 % through rigidity-driven stabilization, as its non-blocking lid improved structural integrity and substrate affinity rather than undergoing interfacial activation. Rhizomucor miehei lipase (RML) and Porcine phospholipase (PPL), which rely on lid-dependent activation, exhibited increased activity (122.3 % and 165.4 %, respectively) due to enhanced lid opening and hydrophobic interactions. Molecular dynamics simulations revealed that PPL’s long lid required the highest flipping energy (−1112.9 kJ/mol), limiting activation. In contrast, RML’s short lid had a lower energy barrier (−596.1 kJ/mol), facilitating lid flipping and interfacial activation. Spectroscopic analysis confirmed that moderate hydrophobicity preserved α-helix structures, whereas excessive reduction induced α-to-β transitions. Radial distribution function analysis indicated that increased solvent accessibility at the active site facilitated RML and PPL activation. For CALB, enhanced van der Waals (vdW) interactions (−207.3 kJ/mol) and reduced electrostatic repulsion within the active pocket strengthened substrate binding, shortening the catalytic serine-substrate distance (2.89 Å vs. 3.38 Å) and improving efficiency. These findings establish that rigidity-dependent enzymes benefit from structural stabilization, whereas lid-dependent lipases require hydrophobicity-tuned flexibility for optimal activation. This study provides a structure–function framework for designing advanced immobilization platforms, with applications in biocatalysis, pharmaceuticals, and biofuel production.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSICAL CHEMISTRY B
·
2025
·
IF 2.9
Qi Qin,Rong-Yao Gao,Yi-Qian Li,Rui Zhang,Yao Lu,Nami Yamano,Xiao-Chun Qin,Dan-Hong Li,Jian-Ping Zhang
Light-harvesting complex IIs (LHCIIs) are the major antenna in higher plants, balancing light capture through photoprotection. While it naturally forms trimers, stress conditions can induce monomerization, altering pigment interactions. Here, we explored how molecular oxygen affects triplet excited-state dynamics in LHCII monomers using time-resolved transient absorption spectroscopy under aerobic and anaerobic conditions. Two chlorophyll-to-carotenoid (Chl → Car) triplet energy transfer (TET) pathways were identified: a fast subnanosecond and a slow tens of nanosecond process. Under anaerobic conditions, inefficient quenching leads to 3Chl* accumulation, with Chl a604 and Chl a602 proposed as sites of long-lived triplet Chl in monomer. In aerobic condition, 3Car* formation is strongly suppressed despite similar 1Chl* lifetimes, suggesting rapid quenching of 3Chl* by oxygen and potential singlet oxygen (1O2) formation. Chl a614 is proposed as an additional site promoting oxygen access and early 1O2 generation. Notably, monomerization enhances the fast TET pathway, possibly compensating for the disrupted pigment coupling at Chl a602/a603 in the Lut621 domain. These results suggest that LHCII trimerization structurally limits oxygen diffusion and promotes efficient triplet quenching via carotenoids, thereby minimizing 1O2 production. Thus, trimeric organization is essential for protecting the photosynthetic apparatus from photooxidative damage under stress.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）