Influence of glucogenic amino acids on the hepatic metabolism of threonine.

The supplementation of a low-protein diet with L-threonine leads to a marked accumulation of threonine in plasma and liver, whereas increasing dietary protein generally leads to an induction of threonine dehydratase in the liver, hence depressed availability for extrasplanchnic tissues. The aim of the present study was, thus, to further investigate the factors which control the utilization of threonine by the liver. Increasing the dietary supply of threonine led to parallel increases in the afferent and hepatic concentrations and in the rate of utilization by the liver; however, the fractional extraction tended to decrease. It appears that the addition of a mixture of glucogenic amino acids to the diet prevented the accumulation of threonine in plasma induced by exogenous threonine. The glucogenic amino acids increased the fractional hepatic uptake of threonine, and counteracted its accumulation in the liver. These effects reflect the fact that the glucogenic amino acids elicited a potent induction of the threonine dehydratase, whereas threonine alone was uneffective. Our results suggest that, besides the well-established effect of glucogenic conditions, the availability of some glucogenic amino acids is an important factor in the control of threonine catabolism.     

Ubiquitin metabolism in HeLa cells starved of amino acids.

Radio-iodinated ubiquitin (Ub) was introduced into HeLa cells by red blood cell-mediated microinjection. The half-life and solubility of Ub, as well as the molecular weight distributions of Ub conjugates, were then measured in HeLa cells grown in complete medium or in medium lacking amino acids and fetal calf serum. Ub metabolism was similar in the two sets of cells. Thus, the dramatic changes in Ub metabolism induced by thermal stress are not observed upon amino acid deprivation.     

Microbial metabolism of 2-methyl amino acids

Eighty-nine microorganisms were isolated that were able to use 2-methyl amino acids and related compounds as the sole source of nitrogen. All of these cultures produced low levels of ammonia in culture supernatant solutions None was capable of fixing nitrogen gas. Whole-cell and cell-free-extract experiments showed that ammonia was not released directly from the 2-methyl amino acids. All of these strains except those isolated with 2-methylserine as a nitrogen source appeared to metabolize 2-methyl amino compounds by a single enzymatic reaction involving simultaneous decarboxylation and transamination. Pyruvate served as an acceptor for the transamination with the concomitant formation of alanine. The strains utilizing 2-methylserine produced a specific 2-methylserine transhydroxymethylase.     

Hepatocyte heterogeneity in the metabolism of amino acids and ammonia.

With respect to hepatocyte heterogeneity in ammonia and amino acid metabolism, two different patterns of sublobular gene expression are distinguished: 'gradient-type' and 'strict- or compartment-type' zonation. An example for strict-type zonation is the reciprocal distribution of carbamoylphosphate synthase and glutamine synthase in the liver lobule. The mechanisms underlying the different sublobular gene expressions are not yet settled but may involve the development of hepatic architecture, innervation, blood-borne hormonal and metabolic factors. The periportal zone is characterized by a high capacity for uptake and catabolism of amino acids (except glutamate and aspartate) as well as for urea synthesis and gluconeogenesis. On the other hand, glutamine synthesis, ornithine transamination and the uptake of vascular glutamate, aspartate, malate and alpha-ketoglutarate are restricted to a small perivenous hepatocyte population. Accordingly, in the intact liver lobule the major pathways for ammonia detoxication, urea and glutamine synthesis, are anatomically switched behind each other and represent in functional terms the sequence of the periportal low affinity system (urea synthesis) and a previous high affinity system (glutamine synthesis) for ammonia detoxication. Perivenous glutamine synthase-containing hepatocytes ('scavenger cells') act as a high affinity scavenger for the ammonia, which escapes the more upstream urea-synthesizing compartment. Periportal glutaminase acts as a pH- and hormone-modulated ammonia-amplifying system in the mitochondria of periportal hepatocytes. The activity of this amplifying system is one crucial determinant for flux through the urea cycle in view of the high Km (ammonia) of carbamoylphosphate synthase, the rate-controlling enzyme of the urea cycle. The structural and functional organization of glutamine and ammonia-metabolizing pathways in the liver lobule provides one basis for the understanding of a hepatic role in systemic acid base homeostasis. Urea synthesis is a major pathway for irreversible removal of metabolically generated bicarbonate. The lobular organization enables the adjustment of the urea cycle flux and accordingly the rate of irreversible hepatic bicarbonate elimination to the needs of the systemic acid base situation, without the threat of hyperammonemia.     

Regulation of intestinal protein metabolism by amino acids

Gut homeostasis plays a major role in health and may be regulated by quantitative and qualitative food intake. In the intestinal mucosa, an intense renewal of proteins occurs, at approximately 50 % per day in humans. In some pathophysiological conditions, protein turnover is altered and may contribute to intestinal or systemic diseases. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions. Many studies have focused on two amino acids: glutamine, known as the preferential substrate of rapidly dividing cells, and arginine, another conditionally essential amino acid. The effects of glutamine and arginine on protein synthesis appear to be model and condition dependent, as are the involved signaling pathways. The regulation of gut protein degradation by amino acids has been minimally documented until now. This review will examine recent data, helping to better understand how amino acids regulate intestinal protein metabolism, and will explore perspectives for future studies.     

Effect of branched-chain amino acids on nitrogen metabolism in irradiated rats

The influence of a mixture of amino acids, with a branched chain, on the protein-nitrogen metabolism in irradiated animals was investigated. Repeated intraperitoneal administrations of the drug was shown to reduce the severity of radiation affection and to normalize nitrogen metabolism decreasing the postirradiation nitrogen losses by the organism.     

Effect of diet and essential amino acids gavage on young rat amino acid metabolism enzymes

• 1.1. The effects of a high-fat, high-energy diet and essential plus semi-essential amino acid gavage on pup rats have been studied (60–65 animals).
• 2.2. The activities of alanine transaminase, adenylate deaminase, glutamine synthetase and serine dehydratase have been tested in liver and muscle.
• 3.3. Plasma was used for the estimation of proteins, urea, amino acids, glucose, lactate, 3-hydroxy-butyrate and acetoacetate.
• 4.4. Liver and muscle glutamine synthetase activities are increased by diet and gavage administered. Hepatic serine dehydratase is inhibited by a cafeteria diet but activated by amino acid gavage. Adenylate deaminase is inhibited by diet and gavage in the liver, but gavage does not affect this enzyme activity in muscle. Liver alanine transaminase is increased by the diet; in the muscle, cafeteria diet and amino acid gavage showed the highest values for this enzyme.
• 5.5. In the plasma, the increase in lactate produced by the diet is inhibited by the amino acids provided. Cafeteria-fed pups showed lower urea levels and higher 3-hydroxybutyrate concentrations in the plasma.
• 6.6. Intracellular glucose is diminished by cafeteria diet. In contrast, the blood cell amino acid concentration increases with diet and gavage supplied.