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UDP‐Glucose pyrophosphorylase is upregulated in carriers of the porcine RN − mutation in the AMP‐activated protein kinase
Author(s) -
Hedegaard Jakob,
Horn Per,
Lametsch René,
Søndergaard Møller Hanne,
Roepstorff Peter,
Bendixen Christian,
Bendixen Emøke
Publication year - 2004
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200300761
Subject(s) - ampk , glycolysis , glycogen , protein kinase a , amp activated protein kinase , biology , biochemistry , citric acid cycle , western blot , kinase , proteome , skeletal muscle , glycogen synthase , downregulation and upregulation , enzyme , microbiology and biotechnology , gene , endocrinology
The AMP‐activated protein kinase (AMPK) plays a key role in the regulation of energy metabolism in eukaryotic cells acting as a metabolic sensor. In its activated form AMPK inhibits ATP consuming pathways and stimulates ATP generating pathways. A dominant mutation, denoted RN − , in the porcine PRKAG3 gene, encoding the regulatory γ3 subunit of AMPK, results in hyperaccumulation of glycogen in glycolytic skeletal muscle cells. To study the effects of this mutation on protein expression patterns in skeletal muscle, comparative proteome analysis of muscle samples from 12 animals (6 rn + / rn + and 6 RN − / rn + ) was performed. The major finding of the proteome analysis was that the key enzyme in the synthesis of glycogen, UDP‐glucose pyrophosphorylase, was significantly up‐regulated in RN − carriers. This observation was subsequently supported by studies of enzyme activity and Northern blot analysis. Furthermore, the expression patterns of enzymes related to glycolysis and the citric acid cycle were also affected. Our data suggests that hyperaccumulation of glycogen mediated by the RN − mutation is due to an increased synthesis of glycogen.