کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2188191 | 1096156 | 2007 | 13 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: M-LDH Serves as a Regulatory Subunit of the Cytosolic Substrate-channelling Complex in Vivo M-LDH Serves as a Regulatory Subunit of the Cytosolic Substrate-channelling Complex in Vivo](/preview/png/2188191.png)
Nucleoside diphosphate kinase A (NDPK-A) regulates the α1 isoform of the AMP-activated protein kinase (AMPK α1) selectively, independent of [AMP] and surrounding [ATP], by a process termed substrate channelling. Here, we show, using a range of empirically validated biochemical techniques, that the muscle form (M-LDH or LDH-A) and the heart form (H-LDH or LDH-B) of lactate dehydrogenase are physically associated with the liver cytosolic substrate-channelling complex such that M-LDH associates with NDPK-A, AMPK α1 and casein kinase 2 (CK2), whereas H-LDH associates with local NDPK-B. We find that the species of LDH bound to the substrate-channelling complex regulates the in vivo enzymatic activities of both AMPK and CK2, and has a downstream effect on the phospho-status of acetyl CoA carboxylase, a key regulator of cellular fat metabolism known to be a part of the cytosolic substrate-channelling complex in vivo. We hypothesise that the regulatory presence of LDH in the complex couples the substrate-channelling mechanism to both the glycolytic and redox states of the cell, allowing for efficient sensing of cell metabolic status, interfacing with the substrate-channelling complex and regulating the enzymatic activities of AMPK and CK2, two critical protein kinases.
Journal: Journal of Molecular Biology - Volume 371, Issue 2, 10 August 2007, Pages 349–361