Summary of Study ST001666
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001070. The data can be accessed directly via it's Project DOI: 10.21228/M8D12Q This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001666 |
| Study Title | Branched-chain alpha-ketoacids are preferentially reaminated and activate protein synthesis in the mouse heart |
| Study Summary | Branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) are elevated in an array of cardiometabolic diseases. Here we demonstrate that sequestration of BCAA and BCKA away from mitochondrial oxidation is likely due to low levels of expression of the mitochondrial BCAA transporter SLC25A44 in the heart, as its overexpression significantly lowers accumulation of [13C]-labeled valine from [U-13C]KIV. |
| Institute | Duke University |
| Last Name | Walejko |
| First Name | Jacquelyn |
| Address | 300 N Duke St |
| jacquelyn.walejko@duke.edu | |
| Phone | 9194792304 |
| Submit Date | 2021-01-26 |
| Analysis Type Detail | GC-MS |
| Release Date | 2021-02-09 |
| Release Version | 1 |
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Project:
| Project ID: | PR001070 |
| Project DOI: | doi: 10.21228/M8D12Q |
| Project Title: | Branched-chain alpha-ketoacids are preferentially reaminated and activate protein synthesis in the heart |
| Project Summary: | Branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) are elevated in an array of cardiometabolic diseases. Here we demonstrate that the major metabolic fate of uniformly-13C-labeled α-ketoisovalerate ([U-13C]KIV) in the heart is reamination to valine. Activation of cardiac branched-chain α-ketoacid dehydrogenase (BCKDH) by treatment with the BCKDH kinase inhibitor, BT2, does not impede the strong flux of [U-13C]KIV to valine. Sequestration of BCAA and BCKA away from mitochondrial oxidation is likely due to low levels of expression of the mitochondrial BCAA transporter SLC25A44 in the heart, as its overexpression significantly lowers accumulation of [13C]-labeled valine from [U-13C]KIV. Finally, exposure of perfused hearts to levels of BCKA found in obese rats increased increases phosphorylation of the translational repressor 4E-BP1 as well as multiple proteins in the MEK-ERK pathway, leading to a doubling of total protein synthesis. These data suggest that elevated BCKA levels found in obesity may contribute to pathologic cardiac hypertrophy via chronic activation of protein synthesis. |
| Institute: | Duke University |
| Department: | Medicine |
| Last Name: | Walejko |
| First Name: | Jacquelyn |
| Address: | 300 N Duke St Durham NC 27701 |
| Email: | jacquelyn.walejko@duke.edu |
| Phone: | 6086097615 |
