Intracellular compartmentation of organelles and gradients of low molecular weight species.

Intracellular compartmentation of metabolites without intervening membranes is an important concept that has emerged from consideration of the metabolic inhomogeneities associated with a highly organized and structured cytoplasm within mammalian cells. This recognition is primarily due to the development of experimental approaches to measure metabolite or ion concentrations at specific subcellular sites, thereby providing a means to study concentration gradients within the aqueous cytoplasm in intact cells. The presence of mitochondrial clusters has been shown to create gradients of low molecular weight species, such as O2, ATP, and pH, with important implications for substrate supply for function and regulation of cellular processes. Moreover, the existence of kinetically distinct precursor pools has been shown to result in functional compartmentation of biochemical pathways, such as DNA replication and carbohydrate metabolism. The creation of these specialized microzones of metabolism in accordance with their association with cellular organelles or membranal structures may be integral to normal function and regulation of adult mammalian cells.