Creatine uptake, metabolism, and efflux in human monocytes and macrophages

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Abstract
The uptake of creatine in human monocytes and monocyte-derived macrophages can be divided into two components. One component of uptake is saturable (Km = 30 microM), specific for creatine, requires Na+ in the extracellular medium, and enables cells to take up creatine against a concentration gradient of creatine. The second component of uptake is nonsaturable and accounts for less than 10% of creatine uptake at physiological creatine concentrations (20-60 microM). Both monocytes and macrophages have similar Km values for creatine transport. However, macrophages exhibit a fivefold greater rate of creatine uptake than monocytes (3.6 vs. 0.7 pmol X micrograms protein-1 X h-1), indicating that monocyte differentiation into macrophages is associated with an increase in the number of creatine transporters in the membrane. Monocytes do not contain creatine kinase and do not phosphorylate creatine; monocyte-derived macrophages express creatine kinase and phosphorylate approximately 25% of intracellular creatine. These results and the finding that 2-deoxyglucose inhibits creatine phosphorylation by macrophages without affecting the transport of creatine indicate that phosphorylation of creatine is not required for net creatine accumulation.