Amino acid metabolism in liver tissue

Following determination by the method of ion-exchange chromatography of free amino acids in the blood drawn from the portal and liver veins and the abdominal aorta 30 minutes after introduction of a casein suspension to rats it was found that only 50 per cent of amino acids with ramified chain are retained in the liver. Most of the other amino acids, however, become metabolized largely in the liver and it is only their insignificant part that goes into the general circulation. These data may be of use in considering problems related to the peculiarities of metabolism of amino acids with ramified chain.     

Amino acid metabolism of myeloma cells in culture

The growth of myeloma cells in Leibovitz medium supplemented with 20% serum was limited by the depletion of glutamine. A simple modification of the Leibovitz medium by increasing the concentrations of glutamine, lysine, isoleucine, leucine, sodium pyruvate, galactose, and vitamins resulted in over 100% increase in cell growth yield. The total myeloma protein produced by the cells was increased by approximately 90% in modified Leibovitz media. Analysis of spent culture media for 19 amino acids showed that the concentrations of 8 amino acids were reduced; those of 5 amino acids were increased and the other 6 did not change significantly.     

Amino acid metabolism and the energetics of growth

The nonessential amino acids are involved in a large number of functions that are not directly associated with protein synthesis. Recent studies using a combination of transorgan balance and stable isotopic tracers have demonstrated that a substantial portion of the extra-splanchnic flux of glutamate, glutamine, glycine and cysteine derives from tissue synthesis. A key amino acid in this respect is glutamic acid. Little glutamic acid of dietary origin escapes metabolism in the small intestinal mucosa. Furthermore, because glutamic acid is the only amino acid that can be synthesized by mammals by reductive amination of a ketoacid, it is the ultimate nitrogen donor for the synthesis of other nonessential amino acids. Because the synthesis of glutamic acid and its product glutamine involve the expenditure of adenosine triphosphate (ATP), it seems possible that nonessential amino acid synthesis might have a significant bearing on the energetics of protein synthesis and, hence, of protein deposition. This paper discusses the topic of the energy cost of protein deposition, considers the metabolic physiology of amino acid oxidation and nonessential amino acid synthesis, and attempts to combine the information to speculate on the overall impact of amino acid metabolism on the energy exchanges of animals.     

Effect of cilazapril therapy on glucose and lipid metabolism in patients with hypertension

The effects of long-term monotherapy with cilazapril, an angiotensin-converting enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 66 patients with hypertension: 23 with normal glucose tolerance and 43 with glucose intolerance (including 9 patients with non-insulin-dependent diabetes mellitus). The levels of plasma glucose, serum insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks) therapy with cilazapril. A 75-g oral glucose tolerance test was performed before and during treatment. Significant reductions in both systolic and diastolic blood pressures in both patient groups were maintained during the study. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patient with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (delta serum insulin/delta venous plasma glucose at 30 minutes post-glucose load) in either group, and glucose intolerance was slightly improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in the patient group with impaired glucose tolerance. Serum total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride levels were significantly (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results suggest that long-term cilazapril therapy may improve glucose and lipid metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril also appears to be useful as an antihypertensive agent for hypertensive patients with either impaired glucose tolerance or hypercholesterolemia.     

Abnormal amino acid metabolism in patients with early stage Alzheimer dementia

Plasma levels of several amino acids were studied in 14 patients with early stage probable Alzheimer's disease (AD) and 17 age-matched controls. In the AD patients a possible relationship between amino acid levels and behavioural symptomatology was also investigated. We found significantly reduced levels of tryptophan and methionine in plasma samples from the AD patients compared to the control subjects. Moreover, plasma tyrosine/large neutral amino acids (LNAA) ratio and the ratio of plasma taurine and the product of the plasma levels of methionine and serine (TSM-ratio) were significantly increased in the AD patients in comparison with the controls. However, no difference was found in plasma tryptophan/LNAA ratio and in homocysteine levels between both groups. Concerning the behavioural symptomatology no significant correlation was found between the Reisberg Behave AD scale and plasma amino acid levels or ratios. The reported findings suggest that abnormal amino acid metabolism is present in the early stages of AD. We hypothesize that this abnormality could play a role in the pathogenesis of behavioural changes occurring in later stages of AD.     

Amino acid incorporation into liver and tumor proteins in patients with hepatic neoplasms-effects of liver dearterialization

The effects of liver dearterialization on the rate of amino acid incorporation into liver and tumor proteins were studied with an in vitro method in seven patients with liver metastases. Before liver dearterialization the incorporation rate was 0.074 +/- 0.020 nmol leucine x mg prot-1 x h-1 in liver tissue and 0.234 +/- 0.049 nmol leucine x mg prot-1 x h-1 in tumor tissue. After dearterialization for 1 h the incorporation rate was reduced to about half of the initial values in both liver and tumor tissue. The vascularity of the tumors was evaluated from preoperative hepatic angiograms. The reduction of the incorporation rate was more pronounced in highly vascularized tumors than in poorly vascularized tumors and liver tissue. The clinical implications of a more pronounced metabolic effect of the dearterialization in high vascularized tumors are discussed.     

The changes of intraerythrocyte calcium metabolism and their responses to nifedipine in patients with essential hypertension

Seven patients with open angle glaucoma were treated using Dorsolamida twice daily together Betablocant treat. Five patients with secondary glaucoma were treated with Dorsolamida three time daily as well three patients with edematous postimplant keratopathy. Intraocular pressure decreased with an average of 3-4 mm Hg and at the patients with corneal edema that decreased.     

Amino acid kinetics during hemodialysis

The kinetic of essential amino acids as well as of histidine and alanine in bilateral nephrectomized rabbits was investigated during a 3 hours hemodialysis. Dialysis, elimination and incorporation rates into plasma proteins were determined for all applied amino acids. Total elimination rates of all the investigated amino acids varied. From 5.31% (leucine) to 75.51% (alanine) of the injected labelled amino acids were eliminated in the dialysate. There was an exponential decrease in the dialysis of essential amino acids and histidine during the period of investigation due to the high incorporation rate into plasma proteins. The kinetic of alanine was different due to a slow incorporation rate leading to a higher elimination rate. The fast incorporation of intravenously applied essential amino acids and histidine during dialysis demonstrates that the existing protein deficiency in renal failure can be influenced positively by infusion of amino acids.     

Circulatory encephalopathy in patients with arterial hypertension

More accurate definition of the leading factors of development of discirculatory encephalopathy (DE) in patients with arterial hypertension was the aim of this investigation. The analysis of correlations between clinical and computer tomographical symptoms of DE on the one hand and the indices of central hemodynamics, head blood circulation and presence of atherosclerosis of head arteria on the other hand was performed. It was found that congestion in head venous system was the main factor in DE development. The conclusion was made that both atherosclerosis of head arteria and arterial hypertension promoted venous congestion in head by means of decreasing the amplitude of arterial pulsation and in turn the development of DE. Meanwhile, the increase of minute blood flow prevents it.     

Arterial hypertension in patients with primary glomerulonephritis

Arterial hypertension is a state of blood pressure permanently higher than 160/90 mm Hg (21.3/12.6 kPa). The renal cause of hypertension occurs in about 10% of all cases. The aim of this article was to establish the frequency, the level, and the connection of the hypertension in different types of primary glomerulonephritis. In this study 90 patients with primary glomerulonephritis were observed. Hypertension was present in 45 patients (50%) and different frequency were noticed in different types of glomerulonephritis. The smallest frequency was recorded in the group with minimal changes and IgA nephritis. In the group with mesangioproliferative glomerulonephritis 52% of patients had hypertension and in the group with focal segmental sclerosis 78%. The most frequent hypertension was observed in the group with rapidly progressive glomerulonephritis. Renal failure was more frequent in patients with hypertension. Different frequencies of hypertension was established in different types of glomerulonephritis. It was not severe and was well controlled by remedies. In most cases it suggest a severe glomerular lesions and fast progression of the disease.     

Amino acid signatures in the normal cat retina

PURPOSE: To establish a nomogram of amino acid signatures in normal neurons, glia, and retinal pigment epithelium (RPE) of the cat retina, guided by the premise that micromolecular signatures reflect cellular identity and metabolic integrity. The long-range objective was to provide techniques to detect subtle aberrations in cellular metabolism engendered by model interventions such as focal retinal detachment. METHODS: High-performance immunochemical mapping, image registration, and quantitative pattern recognition were combined to analyze the amino acid contents of virtually all cell types in serial 200-nm sections of normal cat retina. RESULTS: The cellular cohorts of the cat retina formed 14 separable biochemical theme classes. The photoreceptor --> bipolar cell --> ganglion cell pathway was composed of six classes, each possessing a characteristic glutamate signature. Amacrine cells could be grouped into two glycine- and three gamma-aminobutyric acid (GABA)-dominated populations. Horizontal cells possessed a distinctive GABA-rich signature completely separate from that of amacrine cells. A stable taurine-glutamine signature defined Müller cells, and a broad-spectrum aspartate-glutamate-taurine-glutamine signature was present in the normal RPE. CONCLUSIONS: In this study, basic micromolecular signatures were established for cat retina, and multiple metabolic subtypes were identified for each neurochemical class. It was shown that virtually all neuronal space can be accounted for by cells bearing characteristic glutamate, GABA, or glycine signatures. The resultant signature matrix constitutes a nomogram for assessing cellular responses to experimental challenges in disease models.     

Amino acid signatures in the detached cat retina

PURPOSE: Expressions of certain macromolecules are altered by experimental retinal detachment in the cat. Related alterations in micromolecular signatures of neurons, Müller cells, and the retinal pigment epithelium (RPE) were investigated. METHODS: High-performance immunochemical mapping, image registration, and quantitative pattern recognition were combined to analyze the amino acid contents of virtually all retinal cell types after 3 to 84 days of detachment. RESULTS: Retinal micromolecular signatures showed a spectrum of alterations. The glutamate contents of Müller cells increased and remained elevated for weeks after detachment. Multispectral signatures of Müller cells showed massive metabolic instability in early detachment stages that ultimately resolved as a homogeneous profile significantly depleted in glutamine. Retinal pigment epithelial cell signals also changed dramatically, displaying an initial glutamate spike and then a prolonged decline, even as taurine levels followed an opposite pattern of initial loss and slow restoration. Neurotransmitter signatures of surviving neurons showed extensive precursor-level variation, and, in one case, GABAergic horizontal cells displayed anomalous sprouting. CONCLUSIONS: Dramatic changes in Müller cell amino acid signatures triggered by retinal detachment are partially consistent with losses in glutamine synthetase activity. Taurine signal variations suggest that orthotopic RPE cells attempt to regulate abnormal taurine concentrations in the enlarged subretinal space. Surviving neurons possess characteristic neurotransmitter signals, but their metabolite regulation seems abnormal. On balance, microchemical and structural anomalies develop in the detached cat retina that represent serious barriers to recovery of normal visual function.     

Muscle amino acid metabolism and the control of muscle protein turnover in patients with chronic renal failure

Using a nose-only inhalation system, male Sprague-Dawley rats were exposed 4.2 h d(-1), 5 days per week for 65 weeks to one of two concentrations of natural uranium ore dust aerosol (44% U, 50 mg m(-3) and 19 mg m(-3)) without significant radon content. After inhalation exposure ceased, the rats were allowed to live for their natural lifetime. Lung uranium burdens, measured at the time of death of each animal, declined exponentially after dust inhalation ceased, and the rate of decline was independent of the initial lung burden. Lymph node specific burdens ranged from 1 to 60 fold greater than the specific lung burden in the same animal. No lymph node tumors were observed. The frequency of primary malignant lung tumors was 0.016, 0.175 and 0.328 and primary non-malignant lung tumors 0.016, 0.135 and 0.131 in the control, low and high aerosol exposed groups, respectively. There was no difference in tumor latency between the groups. Absorbed dose to the lung was calculated for each animal in the study. The average doses for all the animals exposed to the low and high dust aerosol concentrations were 0.87 Gy and 1.64 Gy respectively, resulting in an average risk of malignant lung tumors of about 0.20 tumors per animal per Gy in both groups. The frequency of primary lung tumors was also calculated as a function of dose increment for both exposed groups individually and combined. The data indicate that, in spite of the above result, lung tumor frequency was not directly proportional to dose. However, when malignant lung tumor frequency was calculated as a function of dose rate (as measured by the lung burden at the end of dust inhalation) a direct linear relationship was seen (p < 0.01) suggesting dose rate may be a more important determinant of lung cancer risk than dose. Conversely, non-malignant lung tumors were significantly correlated with low lung burdens (p = 0.01). We conclude that chronic inhalation of natural uranium ore dust alone in rats creates a risk of primary malignant and non-malignant lung tumor formation and that malignant tumor risk was not directly proportional to dose, but was directly proportional to dose rate.