This review will consider whether nitric oxide (NO) contributes to maternal systemic vasodilation during pregnancy, regulates uterine and fetoplacental blood flow, and is involved in uterine quiescence prior to parturition. Also, whether a deficiency of NO contributes to the hypertensive disorder of pregnancy, preeclampsia, will be considered. The biosynthesis of NO increases in gravid rats and sheep, but the status in normal human pregnancy and preeclampsia is controversial. NO contributes to maternal systemic vasodilation and reduced vascular reactivity during normal pregnancy; however, the relative contribution of NO is variable depending on the animal species, vascular bed, and vessel size. Impaired relaxation responses to acetylcholine, but not bradykinin or NO donors, are observed in small arteries from women with preeclampsia, suggesting a receptor or signal transduction defect, although NO may play little, if any, role here. Uterine arteries have increased endothelial nitric oxide synthase (NOS) activity, protein expression, and guanosine 3',5'-cyclic monophosphate production during pregnancy; however, whether these mediate uterine vasodilation during pregnancy remains to be established. NOS is expressed in the human placental syncytiotrophoblast and in the fetoplacental and umbilical vascular endothelium where basal production of NO contributes to low fetoplacental vascular resistance. Controversy exists over the status of placental NOS in preeclampsia, although an abnormality of umbilical NOS activity is likely. Finally, the uterus has NOS activity, which decreases at the end of gestation, and exogenous NO relaxes the myometrium, but whether endogenous NO contributes to uterine quiescence during pregnancy has yet to be confirmed.

Nitric oxide and pregnancy

Regulation of enzymes of the urea cycle and arginine metabolism

In the present work, we report the effects of C(60)-pretreatments on acute carbon tetrachloride intoxication in rats, a classical model for studying free-radical-mediated liver injury. Our results show that aqueous C(60) suspensions prepared without using any polar organic solvent not only have no acute or subacute toxicity in rodents but they also protect their livers in a dose-dependent manner against free-radical damage. To be sure, according to histopathological examinations and biological tests, pristine C(60) can be considered as a powerful liver-protective agent.

/pdf/60-fullerene-is-a-powerful-antioxidant-in-vivo-with-no-acute-52vptpv0mw.pdf

[60]fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity.

The reaction of ninhydrin with primary amino groups to form the purple dye now called Ruhemann's purple (RP) was discovered by Siegfried Ruhemann in 1910. In addition, imines such as pipecolic acid and proline, the guanidino group of arginine, the amide groups of asparagine, the indole ring of tryptophan, the sulfhydryl group of cysteine, amino groups of cytosine and guanine, and cyanide ions also react with ninhydrin to form various chromophores of analytical interest. Since its discovery, extensive efforts have been made to apply manual and automated ninhydrin reactions as well as ninhydrin spray reagents to the detection, isolation, and analysis of numerous compounds of interest across a broad spectrum of disciplines. These include agricultural, biochemical, clinical, environmental, food, forensic, histochemical, microbiological, medical, nutritional, plant, and protein sciences. This reaction is unique among chromogenic reactions in that at pH 5.5 it results in the formation of the same soluble chromophore by all primary amines which react, be they amines, amino acids, peptides, proteins, and even ammonia. Because the chromophore is not chemically bound to the protein or other insoluble material, it is not lost when the insoluble substrate is removed by centrifugation or filtration after the reaction is completed. The visible color of the chromophore is distinctive and is generally not affected by the yellow colors present in many food, plant, and tissue extracts. Adaptations of the classical ninhydrin reaction to specialized needs in analytical chemistry and biochemistry include the use of acid, alkaline, and fluorogenic ninhydrin reagents. To cross-fertilize information among several disciplines wherein an interest in the ninhydrin reaction has developed, and to enhance its utility, this review attempts to integrate and correlate the widely scattered literature on ninhydrin reactions of a variety of structurally different compounds. Specifically covered are the following aspects: historical perspective, chemistry and mechanisms, applications, and research needs. A better understanding of these multifaceted ninhydrin reactions provide a scientific basis for further improvements of this important analytical technique.

Applications of the Ninhydrin Reaction for Analysis of Amino Acids, Peptides, and Proteins to Agricultural and Biomedical Sciences

Citrulline (Cit, C6H13N3O3), which is a ubiquitous amino acid in mammals, is strongly related to arginine. Citrulline metabolism in mammals is divided into two fields: free citrulline and citrullinated proteins. Free citrulline metabolism involves three key enzymes: NO synthase (NOS) and ornithine carbamoyltransferase (OCT) which produce citrulline, and argininosuccinate synthetase (ASS) that converts it into argininosuccinate. The tissue distribution of these enzymes distinguishes three “orthogonal” metabolic pathways for citrulline. Firstly, in the liver, citrulline is locally synthesized by OCT and metabolized by ASS for urea production. Secondly, in most of the tissues producing NO, citrulline is recycled into arginine via ASS to increase arginine availability for NO production. Thirdly, citrulline is synthesized in the gut from glutamine (with OCT), released into the blood and converted back into arginine in the kidneys (by ASS); in this pathway, circulating citrulline is in fact a masked form of arginine to avoid liver captation. Each of these pathways has related pathologies and, even more interestingly, citrulline could potentially be used to monitor or treat some of these pathologies. Citrulline has long been administered in the treatment of inherited urea cycle disorders, and recent studies suggest that citrulline may be used to control the production of NO. Recently, citrulline was demonstrated as a potentially useful marker of short bowel function in a wide range of pathologies. One of the most promising research directions deals with the administration of citrulline as a more efficient alternative to arginine, especially against underlying splanchnic sequestration of amino acids. Protein citrullination results from post-translational modification of arginine; that occurs mainly in keratinization-related proteins and myelins, and insufficiencies in this citrullination occur in some auto-immune diseases such as rheumatoid arthritis, psoriasis or multiple sclerosis.

Almost all about citrulline in mammals.

Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance.

The Hitachi L-8500A is a newly available apparatus for amino acid (AA) analysis that allows automatic on-line mixing of the ninhydrin reagent. The within-run precision (human plasma pools at three different concentrations) showed CVs < 3.8% except for the lowest concentration of citrulline (4.4%), Tyr (4.5%), and alpha-aminobutyric acid (7.6%), and for the intermediate concentration of Asp (8.7%). Between-run precision (CV) was < 3.1% for 17 AAs and < 8.0% for 24 of 25 AAs (CV Asp = 12.0%). For retention times, within-run precision was < 0.4% and between-run precision < 1.8%. Excellent relations were found between the results from the Hitachi L-8500A and the widely used Beckman 6300 analyzer (0.929 < or = r < or = 0.999). The detection was still linear at 5 mumol/L except for Pro and hydroxyproline (20 mumol/L). The upper limit was at least 2500 mumol/L for 13 AAs and at least 1000 mumol/L for 27 of 29 AAs (anserine = 500, Val = 600 mumol/L). Values from 100 human plasma samples agreed with previously published data. We conclude that the results obtained with the Hitachi L-8500A are satisfactory when compared with those of other AA analyzers utilizing the same method. Furthermore, the Hitachi L-8500A displays several advantages including programming flexibility, microsample capacity, low noise plotting, ammonia filtering, and manual repacking of the analytical column.

/pdf/amino-acid-determination-in-biological-fluids-by-automated-2kqevkc5s6.pdf

Amino acid determination in biological fluids by automated ion-exchange chromatography: performance of Hitachi L-8500A

Arginine (ARG), a semiessential amino acid, is taken up by cells using the y + transport system. ARG synthesis occurs from citrulline mainly in the liver and in the kidney. ARG is metabolized either in ornithine and urea mainly in the liver and the intestine or in citrulline and nitric oxide (NO • ) in a large number of cell types. Ornithine derived from arginine can be metabolized in citrulline (in the context of the urea cycle), in glutamate or in polyamines. Arginine taken up by the intestine is transformed into citrulline which is poorly taken up by the liver but mainly by the kidney. In the kidney, citrulline is transformed into arginine and subsequently released for peripheral tissues. Intestinal transformation of arginine into citrulline plays a keyrole in the metabolic adaptation to high/low protein diets. In the liver, arginine metabolism plays a pivotal role in the urea cycle, the rate of which is conditioned not only to metabolize extranitrogen, but also to maintain the acid-base homeostasis. Immune cells exhibit the ability to synthesize both polyamines and NO • which are potent immunomodulators. The modulation and balance between these two pathways remain to be elucidated. In the context of clinical nutrition, the use of ARG supplemented diets may be advocated while keeping in mind that in severe injury with organ failure such regimens could be detrimental. (J. Nutr. Biochem. 6:402-403, 1995.)

Arginine metabolism in mammals

https://www.gastrojournal.org/article/0016-5085(95)90701-7/pdf

Evidence for the detrimental role of proteolysis during liver preservation in humans

Background: It is well-established that the combination of proteinenergy malnutrition and low body mass index (BMI) increases the risk of death in elderly patients, but recent studies indicate that the risk of death may decrease with higher body weight. However, these studies did not perform direct, separate, and reliable measurements of fat and lean mass using a reference technique. Objective: Our objective was to evaluate the relation between body composition, based on the 4-compartment model, and morbidity and mortality in hospitalized elderly patients. Design: This prospective study enrolled 125 elderly patients evaluated at admission for body composition on the basis of BMI plus fat mass, lean mass, appendicular skeletal muscle mass, and body cell mass indexes (calculated as the ratio of the mass to the square of the height) measured by X-ray absorptiometry and bioelectrical impedance analysis. Outcomes were assessed 6 mo later by using a score system that takes into account complications (pressure ulcers and/or infections) and 6-mo mortality. Results: The fat mass index correlated positively (r = 0.19 and P = 0.023 adjusted for sex; r = 0.18 and P = 0.043 adjusted for sex, albuminemia, and C-reactive protein) with outcome score (1: death, 2: complications, 3: no complications). There was no significant correlation between outcome score and BMI, lean mass, appendicular skeletal muscle mass, and body cell mass indexes. Conclusions: This study clearly indicates that the generally accepted rule that overweight is associated with morbidity and mortality does not apply to hospitalized elderly patients, for whom fat mass is associated with a decreased risk of adverse events. Am J Clin Nutr doi: 10.3945/ajcn.2009.27819.

Luc Cynober

Papers

Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance.

Amino acid determination in biological fluids by automated ion-exchange chromatography: performance of Hitachi L-8500A

Arginine metabolism in mammals

Evidence for the detrimental role of proteolysis during liver preservation in humans

Fat mass protects hospitalized elderly persons against morbidity and mortality 1-3