Hepatic glycogen synthesis in the absence of glucokinase: the case of embryonic liver.
Glucokinase (GK, hexokinase type IV) is required for the accumulation of glycogen in adult liver and hepatoma cells. Paradoxically, mammalian embryonic livers store glycogen successfully in the absence of GK. Here we address how mammalian embryonic livers, but not adult livers or hepatoma cells, manage to accumulate glycogen in the absence of this enzyme. Hexokinase type I or II (HKI, HKII) substitutes for GK in hepatomas and in embryonic livers. We engineered FTO2B cells, a hepatoma cell line in which GK is not expressed, to unveil the modifications required to allow them to accumulate glycogen. In the light of these results, we then examined glycogen metabolism in embryonic liver. Glycogen accumulation in FTO2B cells can be triggered through elevated expression of HKI or either of the protein phosphatase 1 regulatory subunits, namely PTG or G L. Between these two strategies to activate glycogen deposition in the absence of GK, embryonic livers choose to express massive levels of HKI and HKII. We conclude that although the GK/liver glycogen synthase tandem is ideally suited to store glycogen in liver when blood glucose is high, the substitution of HKI for GK in embryonic livers allows the HKI/liver glycogen synthase tandem to make glycogen independently of the glucose concentration in blood, although it requires huge levels of HK. Moreover, the physiological consequence of the HK isoform switch is that the embryonic liver safeguards its glycogen deposits, required as the main source of energy at birth, from maternal starvation.
Cifuentes
Daniel
D
Institute for Research in Biomedicine, Universitat de Barcelona, Barcelona, Catalonia 08028, Spain.
Martínez-Pons
Carles
C
García-Rocha
Mar
M
Galina
Antonio
A
Ribas de Pouplana
Lluís
L
Guinovart
Joan J
JJ
D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004622:Embryo, Mammalian / Q000201:enzymology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005941:Glucokinase; D006003:Glycogen / Q000096:biosynthesis* / Q000235:genetics; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D006593:Hexokinase / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D051379:Mice; D011247:Pregnancy; D051381:Rats
D001786:Blood Glucose; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; C104748:Ppp1r3c protein, mouse; C491293:Ppp1r5 protein, rat; D006003:Glycogen; D006006:Glycogen Synthase; C515658:HK1 protein, mouse; D006593:Hexokinase; D005941:Glucokinase