The mass transfers of O 2 , glucose, NH 3 , urea and amino acids across the portal-drained viscera (PDV) and the liver were quantified, by arterio-venous techniques, during the last 4 h of a 100 h infusion of 0 (basal), 150 or 400 mol NH 4 HCO 3 /min into the mesenteric vein of three sheep given 800 g grass pellets/d and arranged in a 3 × 3 Latin-square design. Urea irreversible loss rate (ILR) was also determined by continuous infusion of [ 14 C]urea over the last 52 h of each experimental period. PDV and liver movements of glucose, O 2 and amino acids were unaltered by NH 4 HCO 3 administration, although there was an increase in PDV absorption of non-essential amino acids (P = 0⋅037) and a trend for higher liver O 2 consumption and portal appearance of total amino acid-N, glucogenic and non-essential amino acids at the highest level of infusion. PDV extraction of urea-N (P = 0⋅015) and liver removal of NH 3 (P Ͻ 0⋅001), release of urea-N (P = 0⋅002) and urea ILR (P = 0⋅001) were all increased by NH 4 HCO 3 infusion. Hepatic urea-N release (y) and NH 3 extraction (x) were linearly related (R 2 0⋅89), with the slope of the regression not different from unity, both for estimations based on liver mass transfers (1⋅16; SE 0⋅144; P b 1 = 0⋅31) and [14 C]urea (0⋅97; SE 0⋅123; P b 1 = 0⋅84). The study indicates that a sustained 1⋅5 or 2⋅4-fold increase in the basal NH 3 supply to the liver did not impair glucose or amino acid supply to non-splanchnic tissues; nor were additional N inputs to the ornithine cycle necessary to convert excess NH 3 to urea. Half of the extra NH 3 removed by the liver was, apparently, utilized by periportal glutamate dehydrogenase and aspartate aminotransferase for sequential glutamate and aspartate synthesis and converted to urea as the 2-amino moiety of aspartate.
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 .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. UREAGENESIS Ammonia detoxijkationOne vital hepatic function in all mammals is detoxification of NH3, produced from bacterial fermentation or metabolism within the gastrointestinal tract (GIT) and peripheral tissues. Extraction of NH3 by the liver is very efficient with, in sub-overload situations, apparent fractional extractions of 0.75-0.85 (for example, see Reynolds e...
Four 40 kg wethers were used in a crossover design to quantify, by arterio -venous procedures, the mass transfer of NH 3 , urea and amino acids (AAs) across the portal-drained viscera and the liver during a 31 min infusion of either 0 (C0) or 1100 (C1100) mmol NH 4 HCO 3 /min into the mesenteric vein. In C1100, hepatic NH 3 extraction remained stable at 1214 mmol/min (1 : 90 mmol/min per g wet liver weight), the capacity for hepatic NH 3 removal was exceeded by 654 mmol/min ðP , 0 : 05Þ and the incremental (C1100-C0) urea-N release: NH 3 -N removal ratio increased progressively, from 0 : 52 to 0 : 90. The NH 4 HCO 3 infusion reduced total branchedchain AA ðP , 0 : 05Þ transfer across the portal-drained viscera and total AA-N ðP ¼ 0 : 09Þ and lysine ðP ¼ 0 : 02Þ extraction by the liver. Hepatic release of glutamate was augmented ðP ¼ 0 : 03Þ; ornithine switched from net release to net removal ðP , 0 : 001Þ and net splanchnic release of free essential AA (44 mmol/min (SED 9 : 2), P ¼ 0 : 04) and branched-chain AA (33 mmol/min (SED 2 : 0), P ¼ 0 : 001) were reduced to 0 : 58 of their basal rate. The study showed that conversion of excess NH 3 to urea during a short-term hepatic NH 3 overload required no additional contribution of AA-N to ureagenesis; essential AA and branched-chain AA supply to non-splanchnic tissues was, however, temporarily decreased.
This chapter discusses the anatomy and physiology of the liver, and its role in ammonia metabolism and ureagenesis, amino acid metabolism and hepatic protein turnover.
To simulate daily episodes of high absorption associated with the intake of diets with high N content, four wethers (42 ± 3.4 kg body weight), fitted with permanent catheters in the femoral artery and splanchnic vessels, were infused with 340 μmol into the mesenteric vein for 3 h, during the morning meal, over seven consecutive days. On the 7th day, mass transfers of , urea, glucose, lactate, ß-OH-butyrate and O2 were measured across portal-drained viscera (PDV), liver and splanchnic tissues during the last 90 min of the infusion. Measurements were repeated on the following day, at the same time, without the infusion. Plasma concentration in the portal vein (+332 μm; p = 0.006), portal absorption (+424 μmol/min; p < 0.001), liver uptake (+375 μmol/min; p = 0.003) and urea N production (+338 μmol/min; p = 0.059) were higher during infusion. Mass transfers of urea, glucose, lactate, ß-OH-butyrate and O2 across the PDV, and glucose, lactate, ß-OH-butyrate and O2 across the liver, were not altered by the infusion. Results suggest that a daily, discontinuous increase in portal flow during a meal stimulates liver removal and urea N production but does not significantly affect liver glucose production and O2 consumption in sheep.
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