Regulation of hepatic nitrogen metabolism in ruminants.

As befits its anatomical position between the sites of nutrient absorption and deposition the liver provides the metabolic hub of the body. Although the present review is confined to the regulation of N substrates it must not be forgotten that both lipid and carbohydrate metabolism are important and interactive components of hepatic function. Furthermore, hepatic production of insulin-like-growth-factor (1GF)1 and partial removal of glucagon and insulin play an important part in regulation of peripheral endocrine balance. These hormonal events are linked to peripheral appearance of two of the major N products of digestion and absorption, NH3 and amino acids (AA), which are both under the control of hepatic metabolism. Thus, in order to provide the required homeostatic and homeorhetic control, complex mechanisms must operate in vivo but, to date, much of our understanding of these involves use of isolated primary hepatocytes and perfused livers derived from nonruminant sources. The commercial species, pigs, cattle and sheep, offer the unique opportunity to establish chronic arterio-venous preparations across the splanchnic tissues and these have provided the basis for the majority of longitudinal studies in vivo. Nonetheless, the data mass is still small and it is currently necessary to assume that acute findings, both in vivo and in vitro, from laboratory animals can be extrapolated to ruminants. Despite an outward homogeneous appearance the structure of the liver is both complex and ordered. For example, hepatocytes have a polar nature between their sinusoidal and canicular surfaces and this important feature of metabolic regulation is lost when isolated hepatocytes are prepared. Furthermore, there is localization of different subpopulations of hepatocytes, with the dominant (>0.9 in the rat) periportal species being specialized for ureagenesis, gluconeogenesis, glutaminolysis and synthesis of plasma albumin (Haussinger et al. 1992a), as well as exhibiting greater activity of the enzymes of AA catabolism (see Haussinger, 1990). In contrast, the minority perivenous cells, which are restricted to a few cell layers around the efferent hepatic vein, can synthesize glutamine and extract aspartate and glutamate from blood (Stoll et al. 1991). This spatial organization provides a hierarchy for the fates of metabolites and is an important feature for the roles that the liver has to accomplish. The present short review will focus on two of those roles, detoxification of NH3 and the hepatic partition of absorbed AA between catabolism and protein anabolic fates within the liver, as well as the ensuing consequences for the availability of AA sources to the peripheral tissues.