Cell Structure and Metabolic Regulation 39 



step of glucose oxidation. We know at present that probably 

 both of these enzymes would seem to be a part of the mem- 

 branes of the ER. 



Now nothing is known concerning the structural relation- 

 ships of glycogen in the cell; all that is known is that it is 

 deposited in discrete amorphous masses in the cytoplasm. It 

 may be assumed that both glycogen synthesis and breakdown 

 take place at the cytoplasmic matrix surface of the ER 

 membranes, via enzymes which react at those surfaces. In 

 this view, glucose secretion by the liver is analogous to 

 protein enzyme secretion by the pancreas, and perhaps to 

 blood protein secretion by the liver, except that while the 

 large protein molecules are secreted as such, by being pack- 

 aged, the large glycogen aggregates are broken down to smaller 

 molecules beforehand. 



As regards the enzymes involved in the scheme, it is true 

 that only glucose-6-phosphatase and the electron-transferring 

 enzymes are situated in the microsome fraction. However, it 

 is possible that the effective action of the other enzymes 

 takes place at the cytoplasmic matrix surface of the ER, the 

 hexokinase, for example, being "activated" at the ER 

 membrane surface in the same way that it was "activated" 

 at the mitochondrial surface. The additional compounds 

 necessary for enzyme activity, ATP in the case of hexokinase, 

 and the cofactors glucose-1 : 6-diphosphate and adenosine 

 monophosphate (AMP) for phosphoglucomutase and phos- 

 phorylase, are depicted as possibly binding the enzymes to 

 the ER membranes. In the first two cases the coenzymes act 

 as phosphate donors to the substrate, while in all three cases 

 the extra phosphate groups are thought to act by binding, not 

 substrate to enzyme, but enzyme to membrane. 



Now what are the biochemical means by which some of 

 these enzymic reactions can be regulated? Firstly, according 

 to the scheme, the concentration of glucose in the ER lumina 

 is in equilibrium with the concentration of glucose in the blood, 

 and thus the blood level could directly influence the glycogen- 

 glucose equilibrium. In fact, Freedland and Harper (1957) 



