The subcellular compartmentation of creatine kinase isozymes as a precondition for a proposed phosphoryl-creatine circuit.

The idea of a PCr-circuit is supported by the fact that in fully differentiated and highly specialized cells with high sudden energy turnover, e.g., skeletal and cardiac muscle [Wallimann and Eppenberger, 1985], brain and retina photoreceptor cells [Wallimann et al, 1986a], spermatozoa [Tombes and Shapiro, 1985; Wallimann et al, 1986b] and Torpedo electrocytes [Wallimann et al, 1985] mitochondrial CK is generally found in conjunction with cytosolic CK's with a significant fraction of the latter being associated subcellularly in a compartmented fashion at intracellular sites of high energy turnover. It is also becoming apparent that some of the cytosolic CK is specifically associated with membranes possibly via membrane anchors, e.g., with the SR-membrane where CK was shown to be functional by supporting a significant portion of the maximal Ca2(+)-pumping rate [Rossi et al, 1988; submitted]. Similar membrane associations of CK have been shown with the post-synaptic acetylcholine-receptor-rich membrane, the invaginated, and non-innervated face membrane of electrocytes, rich in Na+/K+ ATPase as well as with synaptic vesicles [Wallimann et al, 1985], with the sperm-tail plasma membrane [Wallimann et al, 1986a], and recently also with rod outer segment plasma membranes of bovine photoreceptor cells [Quest et al, 1987; Hemmer et al, 1989]. Thus, for all the above cells the PCr-circuit seems to represent an efficient, flexible, and highly responsive accessory, crucial not only as an energy back-up system, but also as a regulator of energy flux (channeling) and as a fine-tuning device of local ATP-levels. The strength of such a regulated channeling circuit operating at relatively low adenine nucleotide levels compared to the high total PCr and Cr pools, which are metabolically inert, is its high sensitivity towards ADP [Wallimann et al, 1984] that is preventing in excitable cells the accumulation of ADP and AMP unless severe stress, such as hypoxia or ischaemia is imposed. Additional details concerning the PCr-circuit model in muscle and our current ideas about the structure-function relationships of mitochondrial have been described elsewhere [Wallimann and Eppenberger, 1985; Schlegel et al, 1988; Schnyder et al, 1988].(ABSTRACT TRUNCATED AT 400 WORDS)