A structural basis of enzymic heterogeneity within liver endoplasmic reticulum

Abstract

Earlier studies have evidenced a particular kind of biochemical hetero-geneity within the endoplasmic reticulum of liver cells. Enzymes upon which quantitative data are available are present in the same membranes, in both the rough and smooth portions. However, there are two different distribution patterns: NADPH cytochrome c reductase is more concentrated in the smooth membranes; glucose-6-phosphatase is more uniformly distributed through the rough and smooth portions; the other enzyme distributions conform to one of these patterns designated b and c, respectively. We consider a plausible explanation about this heterogeneity, postulating that enzymes in solution in the cisternal medium and integral membrane proteins of the lumenal aspect are randomly distributed through the whole endoplasmic reticulum (type c enzymes), whereas membrane proteins which expose a large segment at the cytoplasmic aspect are heterogeneously distributed. This latter aspect would consist of two distinct, homogeneous domains; one corresponding to the membrane surfaces in close association with ribosomes; the other containing the enzymes of type b. These domains extensively interpenetrate, accounting for the presence of a significant fraction of the enzymes of type b in the rough microsomes. Experimental data concerning the transmembrane asymmetry of enzymes categorized in groups b and c are briefly reviewed. Relationships between the distributions of NADPH cytochrome c reductase, glucose-6-phosphatase and ribosomes in density gradient analysis are deduced from the assumptions made and confronted with actual density distributions obtained.