Altered Hepatic ATP Storage and Creatine Biosynthesis in Transgenic Mouse Liver Expressing Creatine Kinase

Kamaiah Jayalakshmi¹, ², Min-Hui Cui¹, ³, Wei Zhang², Laibin Liu², Craig A. Branch¹, ³, Chandan Guha²

³¹P MRSI has been employed to estimate hepatic phosphagen and ATP concentrations in transgenic mice expressing creatine kinase (CK-Tg) in liver with administration of cyclocreatine. A marked amount of phosphocyclocreatine was stored in liver of CK-Tg mouse with administration of cyclocreatine. In contrast, hepatic ATP concentrations decreased. These were accompanied by decreased serum creatine levels and increased urinary creatine levels. The significant amount of phosphocyclocreatine stored in CK-Tg mouse liver may serve as a false feedback corepressor of creatine biosynthesis since liver is usually lack of phosphagen. Abundant phosphocyclocreatine, a poor creatine kinase substrate, may also impede ATP production.