I'm reading a reference right now on an enzyme I'm interested in, and the reported Km for the enzyme is in the mM range, which is much higher than the typical concentration of the enzyme's substrate that is found in the cell. The reference mentions "Enzymes often work at substrate concentrations below the Km, because the regulation of the enzyme activity is easier then." Can anyone expound on this further? What does it mean? Where can I find more information on this statement? I'm having a hard time understanding that statement since biochemistry is not my expertise. I thought low Km was always better for regulation of the substrate, but why does high Km of the enzyme make it easier to regulate the enzyme?