Article
Chemistry, Organic
Zhiqin Xu, Yaling Mo, Zhengwen Li, Shurong Ban, Heng Song
Summary: This paper investigates the substrate range of Pseudomonas sp. AK1 BBOX (psBBOX) and analyzes the role of aromatic amino acid residues in substrate binding mode. Through the study, a F188A mutant is developed that can hydroxylate cyclic quaternary ammonium analogues and generate new alcohol compounds by breaking the limitation of aromatic cage.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Genetics & Heredity
Edgars Liepinsh, Baiba Svalbe, Gundega Stelfa, Solveiga Grinberga, Liga Zvejniece, Helgi B. Schioth, Maija Dambrova
Summary: Deletion of the exon 2 of the TMLHE gene was found in individuals with ASD. This gene encodes the TMLD enzyme, which is involved in carnitine biosynthesis. Previous studies have suggested that carnitine depletion may play a role in the development of ASD, but the specific role of endogenous carnitine remains inconclusive.
Article
Biotechnology & Applied Microbiology
Pierre Kugler, Marika Trumm, Marcel Frese, Volker F. Wendisch
Summary: L-Carnitine is a bioactive compound derived from L-lysine and S-adenosyl-L-methionine, and this study describes the metabolic engineering of E. coli for L-Carnitine production using enzymes from the fungus Neurospora crassa. The engineered E. coli strain successfully produced L-Carnitine from supplemented substrates and de novo from glycerol and ammonium as carbon and nitrogen sources.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Lauren J. Rajakovich, Beverly Fu, Maud Bollenbach, Emily P. Balskus
Summary: This study elucidated the anaerobic pathway for TMA generation from L-carnitine by human gut bacteria and discovered a novel TMA-lyase enzyme and bbu gene cluster. These findings provide critical insights into the connection between microbial function and human disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Analytical
Tian Tang, Pei Zhang, Siqi Li, Doudou Xu, Wei Li, Yuan Tian, Yu Jiao, Zunjian Zhang, Fengguo Xu
Summary: This study utilized microwave-assisted Tmt-PP derivatization and the QAMS strategy to improve the accuracy of LC-MS/MS determination of ACs, reducing reaction time and resolving the standard availability issue. The established workflow was applied to discover dysregulated ACs in xenograft colon cancer mice, with quantification results highly comparable to traditional methods.
ANALYTICAL CHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Haoran Wei, Mingming Zhao, Junfang Wu, Chenze Li, Man Huang, Jianing Gao, Qi Zhang, Liang Ji, Yan Wang, Chunxia Zhao, Erdan Dong, Lemin Zheng, Dao Wen Wang
Summary: This study found a positive association between plasma TML and HFpEF, and higher plasma TML indicates increased risk of cardiovascular events.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Medicine, General & Internal
Ilmars Stonans, Jelizaveta Kuzmina, Inese Polaka, Solveiga Grinberga, Eduards Sevostjanovs, Edgars Liepins, Ilona Aleksandravica, Daiga Santare, Arnis Kirsners, Roberts Skapars, Andrejs Pcolkins, Ivars Tolmanis, Armands Sivins, Marcis Leja, Maija Dambrova
Summary: Our study aimed to evaluate the association between gastric cancer (GC) and higher concentrations of the metabolites L-carnitine, ?-butyrobetaine (GBB) and gut microbiota-mediated trimethylamine N-oxide (TMAO) in the circulation. We found a significant difference in circulating levels of L-carnitine, GBB, and TMAO between the male control group and the male GC group, suggesting an association between higher blood levels of these metabolites and GC in males. Furthermore, our findings suggest metabolic differences between genders in relation to GC.
Article
Chemistry, Medicinal
Diana Zelencova-Gopejenko, Aiga Grandane, Einars Loza, Daina Lola, Anda Sipola, Edgars Liepinsh, Pavel Arsenyan, Kristaps Jaudzems
Summary: This study reports a new method for analyzing the binding of TMLD substrate analogues to the enzyme, providing insight into the substrate selectivity of TMLD.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Jing Wang, Yan Zhou, Donghui Zhang, Weiyi Zhao, Yishi Lu, Chaoqun Liu, Wandie Lin, Yujie Zhang, Kunling Chen, Hui Wang, Liang Zhao
Summary: The study reveals that CRIP1 is upregulated in HCC and associated with poor prognosis. It promotes HCC cancer stem-like properties by downregulating carnitine energy metabolism. The findings suggest that targeting the CRIP1/BBOX1/beta-catenin axis may be a promising strategy for HCC treatment.
Article
Chemistry, Multidisciplinary
Peter Betlem, Marijn N. Maas, Jim Middelburg, Bas J. G. E. Pieters, Jasmin Mecinovic
Summary: The development of stapled histone peptides bearing trimethyllysine as ligands for epigenetic reader proteins has shown stronger or weaker binding affinities compared to linear histones, indicating that selectivity towards reader proteins can be achieved.
CHEMICAL COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Mingming Zhao, Haoran Wei, Chenze Li, Rui Zhan, Changjie Liu, Jianing Gao, Yaodong Yi, Xiao Cui, Wenxin Shan, Liang Ji, Bing Pan, Si Cheng, Moshi Song, Haipeng Sun, Huidi Jiang, Jun Cai, Minerva T. Garcia-Barrio, Y. Eugene Chen, Xiangbao Meng, Erdan Dong, Dao Wen Wang, Lemin Zheng
Summary: Intestinal microbiota alterations may affect heart function through the production of gut-derived metabolites. The authors found that TMAVA, derived from trimethyllysine through the gut microbiota, is a key determinant for the development of cardiac hypertrophy through inhibition of carnitine synthesis and subsequent fatty acid oxidation.
NATURE COMMUNICATIONS
(2022)
Article
Nutrition & Dietetics
Dong Liu, Jingyuan Wang, Liju Xiao, Siyu Gu, Ze Ma, Zhengyuan Zhou, Shujun Gu, Hui Zuo
Summary: This study aimed to examine the associations between plasma markers of carnitine biosynthesis and the risk of ischemic stroke (IS). The results showed that increased ratios of plasma glycine to carnitine, lysine, and TML were associated with a lower risk of incident IS.
CLINICAL NUTRITION
(2022)
Article
Endocrinology & Metabolism
Ken H. Liu, Joshua A. Owens, Bejan Saeedi, Catherine E. Cohen, Moriah P. Bellissimo, Crystal Naudin, Trevor Darby, Samuel Druzak, Kristal Maner-Smith, Michael Orr, Xin Hu, Jolyn Fernandes, Mary Catherine Camacho, Sarah Hunter-Chang, David VanInsberghe, Chunyu Ma, Thota Ganesh, Samantha M. Yeligar, Karan Uppal, Young-Mi Go, Jessica A. Alvarez, Miriam B. Vos, Thomas R. Ziegler, Michael H. Woodworth, Colleen S. Kraft, Rheinallt M. Jones, Eric Ortlund, Andrew S. Neish, Dean P. Jones
Summary: Delta-valerobetaine, a microbiome-derived metabolite, correlates with obesity-related phenotypes in humans and exacerbates diet-induced obesity in mice.
Article
Nutrition & Dietetics
Jubo Bhuiya, Yoshitomo Notsu, Hironori Kobayashi, Abu Zaffar Shibly, Abdullah Md. Sheikh, Ryota Okazaki, Kazuto Yamaguchi, Atsushi Nagai, Toru Nabika, Takafumi Abe, Masayuki Yamasaki, Minoru Isomura, Shozo Yano
Summary: Recent evidence suggests that trimethylamine-N-oxide (TMAO), a metabolite of L-carnitine and choline, is linked to atherosclerosis and cardiovascular diseases. However, Japanese people who consume lots of fish, which is high in TMAO, show a low risk of atherosclerosis. This study found that TMAO was not a significant risk factor for atherosclerosis in elderly Japanese people, while a low level of trimethyllysine (TML) might be a potential risk. L-carnitine may be a marker for atherosclerosis in women.
Article
Nutrition & Dietetics
Priscilla Day-Walsh, Emad Shehata, Shikha Saha, George M. Savva, Barbora Nemeckova, Jasmine Speranza, Lee Kellingray, Arjan Narbad, Paul A. Kroon
Summary: The study investigated TMA production from dietary precursors using an in-vitro human colon model. Results showed that choline was metabolised via the direct choline TMA-lyase route and l-carnitine conversion to TMA was slower, involving the formation of gamma-BB. The in-vitro model was found suitable for studying gut microbiota metabolism of TMA and screening potential therapeutic targets to attenuate TMA production.
EUROPEAN JOURNAL OF NUTRITION
(2021)