Species Differences in Compartmentation

Most of our concepts on the nature and functional regulation of compartmented sequences derive from studies using the rat. It is natural that one species be used as a standard since this allows a unified approach to the already complex task of understanding metabolic regulation. Concepts derived from studies with the rat have been widely applied to a variety of species, and often with excellent results. There are important exceptions, however, which indicate that caution must be exercised in extending our use of a single species too uncritically. 

A number of recent studies have focused on the compartmentation of key enzymes of gluconeogenesis and lipogenesis and on the differences which occur among mammalian species (for a general review of this work see Hanson, 1974). Some of the specific aspects of the consequences of compartmentation in various species will be discussed later in this chapter. At this point, it is important to draw several general principles which have emerged from studies with animals other than the rat. 

Measurement of the Compartmentation of Intermediates— Limitations of Available Methods 

It is implicit in our discussion of compartmentation that we be able to accurately determine the concentration of intermediates within the various intracellular organelles, especially the mitochondria. Without this ability it is impossible to determine the flux rate of key compoimds across membranes. Is it possible, for example, to accurately determine the intramitochondrial concentration of oxaloacetate during periods of enhanced gluconeogenic flux in order to relate its levels to the known kinetic properties of the enzymes which compete for oxaloacetate Clearly, the formulation of any model for the control of a complex metabolic sequence must consider the actual concentration of all intermediates in the mitochondria if it is to achieve a meaningful interpretation of the kinetic properties of key enzymes. A simple measurement of the whole-cell concentration of an intermediate can be totally misleading, since intracellular gradients occur in various compartments. 

For the measurement of large molecules, such as enzymes and coenzymes, which do not readily move across the mitochondrial mem- 

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