Metabolic depletion of sheep red blood cells leads to decreased intrac
ellular concentrations of ATP and reduced glutathione as well as degra
dation of phosphoinositides. In sheep red blood cells, depletion of AT
P induced two types of shape transformation: one early phase involving
formation of protrusions on the cell surface similar to those observe
d upon depletion of human red blood cells; and one late phase, in whic
h the sheep red blood cells develop long, rod-shaped projections. Duri
ng the initial stages of shape changes, degradation of the phosphoinos
itides parallels the discocyte-echinocyte transformation, thus giving
further support to a shape-controlling mechanism based on the bilayer-
couple hypothesis. However, formation of the long projections does not
coincide with turnover of the phosphoinositides but rather with the l
evel of reduced glutathione. This indicates that development of these
rod-like extensions on the cell surface is induced by oxidative proces
ses that may well involve cross-linking of membrane skeleton proteins.