Figure 1.

Both the intestine and liver play important roles in regulating systemic manganese metabolism. (A) Enterocytes are absorptive cells lining the lumen of intestine. Digested manganese (Mn) in the intestinal lumen can be transported across the apical (AP) membrane into enterocytes and exported across the basolateral (BL) membrane into the blood (solid blue arrows). Absorbed Mn will then be delivered to the liver through the portal vein. Mn in the blood can also be transported into enterocytes and exported back into the intestinal lumen (dashed blue arrows); (B) The liver clears Mn from the blood and secretes Mn into the bile for intestinal reabsorption or fecal excretion. Hepatocytes are polarized and represent the major cell type in the liver. The basal domain of hepatocytes faces the sinusoid blood; whereas, the apical domain forms the bile canalicular network. Hepatocytes express polarized, specific transporters that mediate manganese fluxes into or out of these cells (solid red arrows: manganese transport into hepatocytes from the blood or the bile; dashed red arrow: manganese export from hepatocytes into the bile).