The urea cycle: a two-compartment system

Channelling and enzyme localization remain controversial; they have been proposed for a number of metabolic pathways, especially glycolysis and the tricarboxylic acid cycle. One aspect that is often overlooked in discussions of channelling is that very tight channelling is readily accepted in pathways which occur in enzyme complexes, for example fatty acid synthetase, the 2-oxoacid dehydrogenase complexes and the protein synthesis/ribosome complex. As a metabolon the urea cycle is presently unique since it covers two conventional compartments. For the urea cycle, channelling appears to be almost complete with varying degrees of tightness at each step. Since a considerable portion of the nitrogen for urea synthesis is derived within the hepatocyte from amino acids, does this means that numerous enzyme-enzyme associations are required for this metabolon? Another important, as yet unaddressed, question is what are the consequences of channelling to theories of metabolic regulation? The answers will no doubt be forthcoming in the next few years as the concept of metabolons gains or loses acceptance.