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Metabolism of PLTP, CETP, and LCAT on multiple HDL sizes using the Orbitrap Fusion Lumos.
Singh, Sasha A; Andraski, Allison B; Higashi, Hideyuki; Lee, Lang Ho; Ramsaroop, Ashisha; Sacks, Frank M; Aikawa, Masanori.
Afiliação
  • Singh SA; Center for Interdisciplinary Cardiovascular Sciences, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Andraski AB; Department of Nutrition and Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Higashi H; Center for Interdisciplinary Cardiovascular Sciences, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Lee LH; Center for Interdisciplinary Cardiovascular Sciences, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Ramsaroop A; Center for Interdisciplinary Cardiovascular Sciences, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Sacks FM; Department of Nutrition and Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Aikawa M; Channing Division of Network Medicine, Department of Medicine, and.
JCI Insight ; 6(3)2021 02 08.
Article em En | MEDLINE | ID: mdl-33351780
Recent in vivo tracer studies demonstrated that targeted mass spectrometry (MS) on the Q Exactive Orbitrap could determine the metabolism of HDL proteins 100s-fold less abundant than apolipoprotein A1 (APOA1). In this study, we demonstrate that the Orbitrap Lumos can measure tracer in proteins whose abundances are 1000s-fold less than APOA1, specifically the lipid transfer proteins phospholipid transfer protein (PLTP), cholesterol ester transfer protein (CETP), and lecithin-cholesterol acyl transferase (LCAT). Relative to the Q Exactive, the Lumos improved tracer detection by reducing tracer enrichment compression, thereby providing consistent enrichment data across multiple HDL sizes from 6 participants. We determined by compartmental modeling that PLTP is secreted in medium and large HDL (alpha2, alpha1, and alpha0) and is transferred from medium to larger sizes during circulation from where it is catabolized. CETP is secreted mainly in alpha1 and alpha2 and remains in these sizes during circulation. LCAT is secreted mainly in medium and small HDL (alpha2, alpha3, prebeta). Unlike PLTP and CETP, LCAT's appearance on HDL is markedly delayed, indicating that LCAT may reside for a time outside of systemic circulation before attaching to HDL in plasma. The determination of these lipid transfer proteins' unique metabolic structures was possible due to advances in MS technologies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espectrometria de Massas / Proteínas de Transferência de Fosfolipídeos / Proteínas de Transferência de Ésteres de Colesterol / Fosfatidilcolina-Esterol O-Aciltransferase / Lipoproteínas HDL Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espectrometria de Massas / Proteínas de Transferência de Fosfolipídeos / Proteínas de Transferência de Ésteres de Colesterol / Fosfatidilcolina-Esterol O-Aciltransferase / Lipoproteínas HDL Idioma: En Ano de publicação: 2021 Tipo de documento: Article