Dr. Yuqin Dai is the Director of the Metabolomics Knowledge Center at Stanford ChEM-H. In this role, she collaborates with faculty in the development and execution of experiments aimed at measuring small molecule drug candidates, endogenous and exogenous metabolites in a variety of biomedical R&D contexts. In addition, she provides strategic vision, mentorship, and leadership in the development of new LC/MS analytical methodologies for metabolomics research, the Metabolomics Knowledge Center’s daily operation and growth.
Dr. Dai came to ChEM-H with 20 years of research, marketing and managerial experiences across biotech/pharma and analytical instrument industries. Prior to joining ChEM-H in January of 2020, Dr. Dai worked at Agilent managing strategic collaborations with key opinion leaders in academia and industry for metabolomics researches, driving new application marketing opportunities, and developing differential solutions to support new LC/MS and automation product introductions. Before Agilent, Dr. Dai led bioanalytical R&D teams and managed DMPK projects to support drug discovery and development programs at three biotech/pharm companies. She was also extensively involved in new technology assessment and implementation. Dr. Dai received her Ph.D. in analytical chemistry from the University of Alberta, Canada, where her research focused on the LC/MS and MALDI/MS instrumentation and method development for proteomics and small molecule applications.
Research Engineer, Sarafan ChEM-H
Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells.
The Journal of biological chemistry
In eukaryotes carnitine is best known for its ability to shuttle esterified fatty acids across mitochondrial membranes for β-oxidation. It also returns to the cytoplasm, in the form of acetyl-L-carnitine (LAC), some of the resulting acetyl groups for post-translational protein modification and lipid biosynthesis. While dietary LAC supplementation has been clinically investigated, its effects on cellular metabolism are not well understood. To explain how exogenous LAC influences mammalian cell metabolism, we synthesized isotope-labeled forms of LAC and its analogs. In cultures of glucose-limited U87MG glioma cells, exogenous LAC contributed more robustly to intracellular acetyl-CoA pools than did β-hydroxybutyrate, the predominant circulating ketone body in mammals. The fact that most LAC-derived acetyl-CoA is cytosolic is evident from strong labeling of fatty acids in U87MG cells by exogenous 13C2-acetyl-L-carnitine. We found that the addition of d3-acetyl-L-carnitine increases the supply of acetyl-CoA for cytosolic post-translational modifications due to its strong kinetic isotope effect on acetyl-CoA carboxylase, the first committed step in fatty acid biosynthesis. Surprisingly, whereas cytosolic carnitine acetyltransferase (CRAT) is believed to catalyze acetyl group transfer from LAC to Coenzyme A, CRAT-/- U87MG cells were unimpaired in their ability to assimilate exogenous LAC into acetyl-CoA. We identified carnitine octanoyltransferase (CROT) as the key enzyme in this process, implicating a role for peroxisomes in efficient LAC utilization. Our work has opened the door to further biochemical investigations of a new pathway for supplying acetyl-CoA to certain glucose-starved cells.
View details for DOI 10.1016/j.jbc.2022.102848
View details for PubMedID 36587768