Densities of NADPH-ferrihemoprotein reductase and cytochrome P-450 molecules in the endoplasmic reticulum membrane of rat hepatocytes.

In hepatocytes, NADPH-ferrihemoprotein reductase (reductase) has been hypothesized to exist as aggregates or micelles in endoplasmic reticulum (ER) membrane. However, if the number of reductase molecules per unit area of ER is low, this hypothesis cannot explain how a few reductase molecules efficiently reduce many P-450 molecules. To test this hypothesis, we estimated the numbers of reductase and P-450 molecules per unit ER area (reductase and P-450 densities) by microphotometry of the two enzymes in conjunction with morphometry of ER in periportal, midzonal, and perivenular rat hepatocytes. The reductase density in periportal, midzonal, and perivenular hepatocytes (107-179 molecules/microns 2 of ER) was high enough to efficiently reduce all P-450 molecules in the ER, although the value in perivenular hepatocytes was lowest owing to the relatively greater amount of ER in this region. The pattern of sublobular gradient in the reductase density was similar to that in the P-450 density. Consequently, the molar ratio of P-450 to reductase in ER was similar (about 40:1) in hepatocytes regardless of their positions within the liver lobule.