Part of medium chain fatty acids (MCFAs) coming from dietary triglycerides (TGs) can be directly absorbed through the gastric mucosa after the action of preduodenal lipase (lingual lipase in the rat). MCFA gastric absorption, particularly that of octanoic acid (C8:0), may have a physiological importance in the octanoylation of ghrelin, the orexigenic gastric peptide acting as an endogenous ligand of the hypothalamic growth hormone secretagogue receptor 1a (GHSR-1a). However, the amount of C8:0 absorbed in the stomach and its metabolic fate still haven't been clearly characterized. The purpose of the present study was to further characterize and quantify the importance of preduodenal lipase activity on the release and gastric absorption of dietary C8:0 and on the subsequent ghrelin octanoylation in the stomach mucosa. Fifteen days old rats received fat emulsions containing triolein or [1,1,1-(13)C]-Tri-C8:0 and a specific inhibitor of preduodenal lipase, 5-(2-(benzyloxy)ethoxy)-3-(3-phenoxyphenyl)-1,3,4-oxadiazol-2(3H)-one or BemPPOX. The fate of the (13)C-C8:0 was followed in rat tissues after 30 and 120min of digestion and octanoylated ghrelin was measured in the plasma. This work (1) demonstrates that part of C8:0 coming from Tri-C8:0 is directly absorbed at the gastric level, (2) allows the estimation of C8:0 gastric absorption level (1.3% of the (13)C-C8:0 in sn-3 position after 30min of digestion), as well as (3) the contribution of rat lingual lipase to total lipolysis and to duodenal absorption of dietary FAs (at least 30%), (4) shows no short-term effect of dietary Tri-C8:0 consumption and subsequent increase of C8:0 gastric tissue content on plasma octanoylated ghrelin concentration.
Title: Study of biochemical biomarkers in freshwater prawn Macrobrachium borellii (Crustacea: Palaemonidae) exposed to organophosphate fenitrothion Lavarias S, Garcia C, Crespo R, Pedrini N, Heras H Ref: Ecotoxicology & Environmental Safety, 96:10, 2013 : PubMed
Several agrochemicals like organophosphates are extensively used to control pests in agricultural practices but they also adversely affect non-target fauna. The effect of organophosphorous fenitrothion on the prawn Macrobrachium borellii was evaluated. The 96-h LC50 was determined. Activity of superoxide dismutase, catalase, glutathione-S-transferase and lipid oxidation levels, were evaluated in the hepatopancreas from adults exposed to sublethal fenitrothion concentrations for 1, 2, 4 and 7 days. In addition, superoxide dismutase mRNA expression, acetylcholinesterase inhibition and haemocyte DNA damage were determined. The 96-h LC50 was 4.24mug/l of fenitrothion. Prawn exposed to sublethal FS concentrations showed an increase of both catalase and superoxide dismutase activities, mainly after 2 and 4 days exposure and an increase of glutathione-S-transferase activity from day 2 to day 7 while lipid oxidation levels increased mainly on day 1. Superoxide dismutase transcripts were significantly higher in fenitrothion -treated prawns, indicating an induction mechanism. Hemolymph analysis showed that while acetylcholinesterase activity decreased after 2 days, haemocytes displayed most DNA damage after 7-day exposure to fenitrothion. These results indicate that prawn enzymes are highly sensitive to fenitrothion exposure, and these biological responses in M. borellii could be valuable biomarkers to monitor organophosphorous contamination in estuarine environments.
Among the large variety of reversible inhibitors that bind to cholinesterases (ChE), only a few exhibit exquisitely strong binding reflected in low femtomolar to picomolar equilibrium dissociation constants. These tight binding inhibitors owe their high affinity to distinctive modes of interaction with the enzyme: naturally occurring snake toxins, the fasciculins, share a large 1000 angstroms2 complementary surface for its complex with acetylcholinesterases (AChE; EC 3.1.1.7); transition state analogs trifluoroacetophenones form a covalent bond with the active serine; disubstituted 1,2,3-triazole inhibitors formed in situ are selected by AChE for optimal interaction surface over the length of the active center gorge. All these inhibitors bind with higher affinity to AChEs than to the closely related butyrylcholinesterases (BuChE; EC 3.1.1.8). Selectivity of individual inhibitors towards BuChE increases with increasing their molecular size. Interaction kinetics for all three classes of compounds reveal very slow rates of dissociation of the AChE-inhibitor complexes or conjugates combined with very fast association rates. The influence of conformational flexibility of the active center gorge on the affinity of inhibitor binding was demonstrated by comparing binding properties of a series of disubstituted 1,2,3-triazoles having systematically varied structures. Analysis of the linear free energy relationships of binding to both mouse and Electrophorus AChE reveals independent contributions of individual structural elements of inhibitors to their binding with the triazole ring emerging as an independently contributing pharmacophore. These tight binding inhibitor interactions reveal useful information not only on the conformational flexibility of ChEs, but also on the diversity of modes of interaction that achieve inhibition.
Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.
Title: [Evaluation of blood esterases in Alzheimer's disease] Saldanha C, Quintao T, Garcia C Ref: Acta Medica Portuguesa, 5:591, 1992 : PubMed
The aim of this work was to evaluate a possible correlation between erythrocyte acetylcholinesterase activity (AChE) and membrane fluidity expressed by fluorescence polarization of--1,6--diphenyl 1,3,5--hexatriene (DPH). Blood samples of 34 Alzheimer's patients (18F and 16M) were obtained and haemoglobin concentration, haematocrit, plasma (butyrylcholinesterase, BCHE) and erythrocyte (AChE) esterase activities and fluorescence polarization after introduction of DPH in erythrocyte membrane have been determined. Results were compared with values obtained from blood samples of 34 apparently healthy volunteers with the same age variation (53-82 years). There was no correlation between AChE activity and fluorescence polarization in the control group nor in the patients' group. There was a significant negative correlation (r = -0.82; p < 0.001) between mean corpuscular hemoglobin concentration (MCHG) and erythrocyte acetylcholinesterase activity in Alzheimer's patients. This correlation suggests that any variation of internal globular viscosity (or MCHG) may indirectly affect AChE enzymatic activity and consequently contribute to the loss of interrelation between AChE activity and membrane lipid fluidity, verified in the present work. A biological marker for Alzheimer's disease diagnosis remains to be discovered.
