Creatine kinase and ATP synthase reaction rates in human frontal lobe measured by ³¹P magnetization transfer spectroscopy at 4T

Abstract

The human frontal lobe is critical for cognitive function in the healthy brain. Many psychiatric disorders including schizophrenia and bipolar disorder are associated with apparent mitochondrial dysfunction and bioenergetic abnormalities in the frontal lobe. Therefore, measuring cerebral bioenergetics associated with creatine kinase and adenosine triphosphate (ATP) synthase reactions could provide crucial information regarding the underlying molecular mechanisms associated with psychiatric disorders. In this study, the unidirectional forward chemical exchange metabolic fluxes of creatine kinase and ATP synthase reactions as well as reverse chemical exchange metabolic flux associated with ATP hydrolysis were determined at 4T by (31)P magnetization transfer. The current experiments indicate that the kinetic network of PCr↔ATP↔Pi can be measured reliably in the human frontal lobe at 4T, which will enable detailed in vivo characterization of bioenergetic abnormalities in a variety of neuropsychiatric disorders.