The effects of dietary lipid and phenobarbitone on the production and utilization of NADPH in the liver. A combined biochemical and quantitative cytochemical study.

The validity of the concept that cellular NADPH utilization in the cytoplasm can, by quantitative cytochemical procedures, be classified into two pathways (Pathway I, in which NADPH is oxidized via the microsomal electron-transport system, and Pathway II, in which NADPH supplies reducing equivalents for biosynthetic processes) was tested. The amount of NADPH, generated by glucose 6-phosphate dehydrogenase, entering Pathways I and II in the centrilobular and periportal regions was measured by quantitative cytochemistry, and the values obtained were compared with biochemical measurements of mixed-function oxidase and fatty acid synthetase activity after the administration of sodium phenobarbitone or by altering the quantity and nature of the dietary lipid. Phenobarbitone stimulates hepatic mixed-function oxidation measured biochemically and Pathway I, but not Pathway II. Variation in the type and quantity of dietary lipid can also regulate the activity in mixed-function oxidation and alter the amount of NADPH entering Pathways I and II. It is concluded that, in general, the concept of two main pathways of NADPH utilization in the liver is valid, but that the ratios of NADPH utilization in the two pathways gives a better indication of the use of NADPH in vivo than is obtained for absolute values for the two pathways. Moreover, the centrilobular and periportal hepatocytes showed different patterns in their response to changes in dietary lipid and the administration of phenobarbitone. These results indicate the different metabolic roles that these two groups of cells may play in the metabolism of foreign compounds.