Acid Compartment Research Articles

Bipolar membrane electrodialysis for treatment of sodium acetate waste residue

Abstract Large amounts of solid waste residue containing high salinity and a series of organic impurities are produced during the manufacturing process of dithianon in insecticide factories, posing a severe environmental pollution problem. Here sodium acetate (CH 3 COONa) waste residue is firstly tested by diffusion dialysis (DD) to investigate the permeability of different commercial ion exchange membranes. Selemion CMV and AMV membranes show low permeability to the organic impurities of the waste residue, and hence are chosen for the following bipolar membrane electrodialysis (BMED) experiments to regenerate acid and base. The BMED firstly uses a BP-A-C-BP configuration to select an optimized current density of ∼50 mA/cm 2 . Afterwards, four membrane stack configurations are compared including BP-A-C-BP, C-BP-A-C, BP-C-BP and BP-A-BP. In consideration of the high current efficiency, low energy consumption, and high concentrations of the produced acid/base, C-BP-A-C is a favorable configuration. Finally, the addition of a strong acid 001 ∗ 7 type of cation-exchange resin into acid compartment can substantially decrease the voltage drop across the stack and reduce the energy consumption. The C-BP-A-C configuration at 50 mA/cm 2 can have a high output (0.491 mol/L CH 3 COOH and 0.556 mol/L NaOH), high current efficiency (87.7% for CH 3 COOH and 99.0% for NaOH), and a relatively low energy consumption (22.3 kW h/kg CH 3 COOH and 29.7 kW h/kg NaOH). Overall, this study illustrates the practical significance of BMED process for treating sodium acetate waste residue, including reducing soil and water pollution and producing valuable products in insecticide industries.

Multiple deletions in the polyketide synthase gene repertoire ofMycobacterium tuberculosisreveal functional overlap of cell envelope lipids in host-pathogen interactions

Several specific lipids of the cell envelope are implicated in the pathogenesis of M. tuberculosis (Mtb), including phthiocerol dimycocerosates (DIM) that have clearly been identified as virulence factors. Others, such as trehalose-derived lipids, sulfolipids (SL), diacyltrehaloses (DAT) and polyacyltrehaloses (PAT), are believed to be essential for Mtb virulence, but the details of their role remain unclear. We therefore investigated the respective contribution of DIM, DAT/PAT and SL to tuberculosis by studying a collection of mutants, each with impaired production of one or several lipids. We confirmed that among those with a single lipid deficiency, only strains lacking DIM were affected in their replication in lungs and spleen of mice in comparison to the WT Mtb strain. We found also that the additional loss of DAT/PAT, and to a lesser extent of SL, increased the attenuated phenotype of the DIM-less mutant. Importantly, the loss of DAT/PAT and SL in a DIM-less background also affected Mtb growth in human monocyte-derived macrophages (hMDMs). Fluorescence microscopy revealed that mutants lacking DIM or DAT/PAT were localized in an acid compartment and that bafilomycin A1, an inhibitor of phagosome acidification, rescued the growth defect of these mutants. These findings provide evidence for DIM being dominant virulence factors that mask the functions of lipids of other families, notably DAT/PAT and to a lesser extent of SL, which we showed for the first time to contribute to Mtb virulence.

An innovative beneficial reuse of seawater concentrate using bipolar membrane electrodialysis

Because of the demand for acid solutions in seawater desalination pretreatment and the difficulty of transporting sulfuric acid or hydrochloric acid, seawater concentrate from an RO system was used as the feed for the production of mixed acid by bipolar membrane electrodialysis (BMED) after the removal of calcium ions and magnesium ions. In this experiment, the feasibility of the process was tested using a laboratory ED-cell with an effective area of 88cm2. Based on the configuration of the BP-C-A-BP, the mixed acid solution was produced in the acid compartment, and the base solution was produced in the base compartment. The results showed that 1mol/L mixed acid and sodium hydroxide could be produced continuously at a constant current density of 57mA/cm2 and a flow rate of 0.30L/h in the continuous-mode BMED. After the production of the acid and base solution, membrane fouling was inspected by measuring the stack resistance and using electron microscopy and surface elemental analysis. No visible fouling deposits on the surface of the CEMs (AEMs) were observed, and there was an increased stack resistance, thus proving that the BMED process for mixed acid production with pretreated RO concentrate is suitable for a long-term run.

Production of lactobionic acid by means of a process comprising the catalytic oxidation of lactose and bipolar membrane electrodialysis

Lactobionic acid (LBA) is a high value-added oxidation product of lactose with numerous potential applications in the food, pharmaceutical and chemical industries. This study aimed to investigate the viability of producing LBA from a sodium lactobionate (LBNa) solution obtained by the aerobic oxidation of lactose over gold nanoparticles supported on mesoporous silica, using a three-compartment bipolar membrane electrodialysis (BMED) stack with an effective area of 0.01m2. The results indicated that LBNa was continuously split in LB− (lactobionate anion) and Na+ ions during BMED, which formed LBA and NaOH in the acid and base compartments, respectively. A demineralization rate of about 50% was achieved after applying a voltage difference of 5.0V during 100min followed by 5.5V during 80min, while the LBA concentration increased about 2.5 times in the acid compartment. The specific energy consumption was 0.57kWhkg−1 over the whole stack. Although sodium was found in small amounts (17.5ppm) in the acid compartment, these results show for the first time the viability of producing LBA by means of an integral process comprising the catalytic oxidation of lactose and BMED, with the advantage that the NaOH could be efficiently recovered for its reutilization in further oxidation reactions.

Pancreatic protease activation by alcohol metabolite depends on Ca 2+ release via acid store IP 3 receptors

Toxic alcohol effects on pancreatic acinar cells, causing the often fatal human disease acute pancreatitis, are principally mediated by fatty acid ethyl esters (non-oxidative products of alcohol and fatty acids), emptying internal stores of Ca(2+). This excessive Ca(2+) liberation induces Ca(2+)-dependent necrosis due to intracellular trypsin activation. Our aim was to identify the specific source of the Ca(2+) release linked to the fatal intracellular protease activation. In 2-photon permeabilized mouse pancreatic acinar cells, we monitored changes in the Ca(2+) concentration in the thapsigargin-sensitive endoplasmic reticulum (ER) as well as in a bafilomycin-sensitive acid compartment, localized exclusively in the apical granular pole. We also assessed trypsin activity in the apical granular region. Palmitoleic acid ethyl ester (POAEE) elicited Ca(2+) release from both the ER as well as the acid pool, but trypsin activation depended predominantly on Ca(2+) release from the acid pool, that was mainly mediated by functional inositol 1,4,5- trisphosphate receptors (IP(3)Rs) of types 2 and 3. POAEE evoked very little Ca(2+) release and trypsin activation when IP(3)Rs of both types 2 and 3 were knocked out. Antibodies against IP(3)Rs of types 2 and 3, but not type 1, markedly inhibited POAEE-elicited Ca(2+) release and trypsin activation. We conclude that Ca(2+) release through IP(3)Rs of types 2 and 3 in the acid granular Ca(2+) store induces intracellular protease activation, and propose that this is a critical process in the initiation of alcohol-related acute pancreatitis.

The energy-saving production of tartaric acid using ion exchange resin-filling bipolar membrane electrodialysis

In view of some inherent disadvantages of traditional technique, production of tartaric acid was attempted through the laboratory-scale bipolar membrane electrodialysis (BMED) in this work. Due to the relatively low solubility of bitartrate, the three-compartment configuration but not the two-compartment configuration which is preferred for weak acid production was selected. Thus, one of the aims of this work lies in the exploration of the energy-saving producing method for weak acid by BMED with the three-compartment configuration. Enlightened by electro-deionization technology, strong acid resin was filled in the acid compartment which is partly responsible for high energy consumption in the weak acid production to facilitate the transport of ions. Accordingly, the cell voltage, current efficiency and energy consumption were investigated and compared during the tartaric acid production before and after the addition of resin, respectively. The preliminary results showed that the expectation that the run of BMED with three-compartment configuration at relatively high current density with relatively low energy consumption can be implemented to a certain extent by the aforementioned method.

Electrochemical acidification of milk by whey desalination

We describe a process configuration for the electrochemical acidification of milk using the desalination function and the acid/base production function of a bipolar membrane process. First, the milk is acidified by the acid produced in the bipolar membrane stack. The precipitate is removed by a solid/liquid separation. The supernatant whey is fed to the bipolar membrane stack for desalination. Next to desalination the stack is also used for acid and base production where the acid returns to the initial precipitation process and the base is used to neutralise the desalinated whey. Particular attention is paid to the discrimination of calcium scaling and protein fouling behaviour of different cation exchange membranes operating in the stack. Monovalent ion selective membranes show low scaling behaviour. The influence of different membrane configurations on the process efficiencies and the power consumption is tested. Current efficiency of the process suffers from proton leakage at anion exchange membranes. Using part of the casein whey to buffer the acid compartment process current efficiencies of 0.86 for the production of acid and 0.87 for the production of base can be achieved.

NAADP, cADPR and IP3 all release Ca2+ from the endoplasmic reticulum and an acidic store in the secretory granule area

Inositol trisphosphate and cyclic ADP-ribose release Ca2+ from the endoplasmic reticulum via inositol trisphosphate and ryanodine receptors, respectively. By contrast, nicotinic acid adenine dinucleotide phosphate may activate a novel Ca2+ channel in an acid compartment. We show, in two-photon permeabilized pancreatic acinar cells, that the three messengers tested could each release Ca2+ from the endoplasmic reticulum and also from an acid store in the granular region. The nicotinic acid adenine dinucleotide phosphate action on both types of store, like that of cyclic ADP-ribose but unlike inositol trisphosphate, depended on operational ryanodine receptors, since it was blocked by ryanodine or ruthenium red. The acid Ca2+ store in the granular region did not have Golgi or lysosomal characteristics and might therefore be associated with the secretory granules. The endoplasmic reticulum is predominantly basal, but thin extensions penetrate into the granular area and cytosolic Ca2+ signals probably initiate at sites where endoplasmic reticulum elements and granules come close together.

Autocrine and paracrine nitric oxide regulate attachment of human osteoclasts.

Nitric oxide (NO) can reduce bone loss in chronic bone diseases. NO inhibits or kills osteoclasts, but the mechanism of action of NO in human bone turnover is not clear. To address this, we studied effects of NO on attachment and motility of human osteoclasts on mineralized and tissue culture substrates under defined conditions. Osteoclasts were differentiated in vitro from CD14 selected monocytes in RANKL and CSF-1, and characterized by cathepsin K expression, tartrate-resistant acid phosphatase (TRAP) activity, acid secretion, and lacunar resorption. Cell attachment was labeled with monoclonal antibody 23C6, specific for a binding domain of a key osteoclast attachment protein, the CD51/CD61 integrin dimer (alpha(v)beta(3)), with or without cell permeabilization. A ring of integrin attachment during bone degradation delimits an extracellular acid compartment, while alpha(v)beta(3) forms focal attachments on non-resorbable substrates. On resorbable substrate but not non-resorbable substrate, alpha(v)beta(3) labeling required cell permeabilization, in keeping with the membrane-matrix apposition that excludes large molecules and allows extracellular acidification. Acid secretion was labeled with the fluorescent weak base indicator lysotracker. NO donors, S-nitroso-N-acetyl penicillamine (SNAP) or sodium nitroprusside (SNP), downmodulated acid secretion simultaneously with cytoskeletal rearrangement, with alpha(v)beta(3) redistributed to a discontinuous pattern that labeled, on bone substrate, without membrane permeabilization. These effects were reversible, and an inhibitor of NO synthesis, N(G)-monomethyl-L-arginine (l-NMMA), increased acid secretion and decreased heterogeneity of attachment structures, showing that NO is an autocrine regulator of attachment. A hydrolysis-resistant activating cGMP analog 8-(4-chlorophenylthio)guanosine-3',5'-cyclic monophosphate replicated effects of NO donors, while an inhibiting analog, 8-(4-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate, Rp-isomer, opposed them. On tissue culture or mineralized substrates, NO or cGMP analogs directly regulated motility; after washout cells reattached and survived for days. We conclude that NO is produced by human osteoclasts and regulates acid secretion and cellular motility, in keeping with autocrine and paracrine NO regulation of the resorption cycle.

Transport Characteristics of Neutralization Dialysis and Desalination of Tap Water

Abstract In neutralization dialysis, the salt solution is desalinated continuously. The cations in desalination compartment are exchanged with protons in the acid compartment across a cation-exchange membrane and the anions are exchanged with hydroxide ions in the base compartment across an anion-exchange membrane. A simple index (C/J), where C is the source phase concentration (mol cm−3) and J is the flux (mol cm−2 min−1), was proposed for the estimation of the desalination properties in neutralization dialysis. The index was based on the concepts of the ion-exchange reaction rate at the membrane interface and was related to the permeation constant in the source-phase boundary layer at the membrane interface, Pa (cm min−1), as C/J = 1/(k1·Cex) + 1/Pa, where k1 is the rate constant of ion-exchange reaction (mol−1 cm4 min−1) and Cex is the ion exchange capacity of the membrane (mol cm−3). The desalination efficiency increased with the decrease of the desalination compartment thickness and the decrease of the linear velocity, which can be estimated well by using the index. Tap water was desalinated by neutralization dialysis and pure water was obtained at the outlet of the desalination cell.

Neutralization Dialysis by Three-Compartment Cell

In neutalization dialysis, the rations in desalination compartment are exchanged with protons in the acid compartment across a cation-exchange membrane, the anions are exchanged with hydroxide ions in the base compartment across an anion-exchange membrane, and the salt solution is desalinated continuously. The desalination properties in neutralization dialysis was estimated by a simple index (C/J), where C is the source phase concentration and J is the flux. Tap water was desalinated by neutalization dialysis cell with three compartments and pure water was obtained at the outlet of a desalination cell with the pumping rate ofca. 100 cm3 min-1.

Recovery of lactic acid from sodium lactate by ion substitution using ion-exchange membrane

Abstract Electrodialysis experiments were carried out to achieve efficient production of lactic acid from sodium lactate. Conventional electrodialysis (CED) consisting of cation- and anion-exchange membrane and ion substitution electrodialysis (ISED) consisting of only cation-exchange membrane were performed and the results were compared in terms of lactic acid loss and the ratio ( η I ) of sodium ions transported to the current supplied. While both electrodialysis operations removed over 95% of sodium ions from the feed solution, the CED operation, however, resulted in a considerable loss of lactic acid, whereas there was no such loss in the ISED operation. Furthermore it was found that the ratio of sodium ions transported to the current supplied was above 1.5 during the early stage of operation in the ISED experiment, indicating that the sodium ions are transported not only by electric force but also by concentration gradient in the ISED operation. By comparing the results of the two electrodialysis operation modes, it was found that the ISED operation is advantageous for the production of lactic acid from sodium lactate in terms of preventing lactic acid loss. In the ISED operation, however, process efficiency decreased with the accumulation of sodium ions in the acid compartment because sodium ions in the acid solution are transported back to the feed stream. This finding suggests the desirability of using a proton permselective cation-exchange membrane, which is preferentially permeable to proton ions among the various cations present in the solution.

Ca 2+ transport into an intracellular acidic compartment of Candida parapsilosis

In this report, we study Ca 2+ transport in permeabilized Candida parapsilosis spheroplasts prepared by a new technique using lyticase. An intracellular non-mitochondrial Ca 2+ uptake pathway, insensitive to orthovanadate and sensitive to the V-H +-ATPase inhibitor bafilomycin A 1, nigericin and carbonyl cyanide p-trifluoromethoxyphenylhydrazone was characterized. Acidification of the compartment in which Ca 2+ accumulated was followed using the fluorescent dye acridine orange. Acidification was stimulated by the Ca 2+ chelator EGTA and inhibited by Ca 2+. These results, when added to the observation that Ca 2+ induces alkalization of a cellular compartment, provide evidence for the presence of a Ca 2+/nH + antiporter in the acid compartment membrane. Interestingly, like in acidocalcisomes of trypanosomatids, the antioxidant 3,5-dibutyl-4-hydroxytoluene inhibits the V-H +-ATPase. In addition, the antifungal agent ketoconazole promoted a fast alkalization of the acidic compartment. Ketoconazole effects were dose-dependent and occurred in a concentration range close to that attained in the plasma of patients treated with this drug.

Transfer of cobalamin from intrinsic factor to transcobalamin II

The process is obscure by which cobalamin (Cbl) in the endocytosed intrinsic factor (IF)-cobalamin (Cbl) complex is released and transferred to transcobalamin II (TCII) within the enterocyte. Using recombinant IF and TCII, binding of Cbl to IF at pH 5.0 was 70% of binding at pH 7.0, whereas for TCII alone, the value was only 12%. TCII binding activity was lost rapidly at lower pH, but this was not due to protease action. TCII incubated at pH 5.0 with cathepsin L was degraded and could not subsequently bind Cbl. Thus, transfer from IF to TCII is unlikely to occur within an acid compartment. Only 13–15% of bound Cbl was released at pH 5.0 and pH 6.0 from either rat IF, human IF, or human TCII. The K a of human or rat IF at pH 7.5 was 2.2 nM; for TCII, the value was 0.34 nM. At pH 7.5, Cbl transfers from IF to TCII, but only to a limited extent (21%), as detected by nondenaturing electrophoresis. Transfer of Cbl from IF to TCII could not be demonstrated at pH values of 5.0 or 6.0. Thus, luminal transfer of Cbl between IF and TCII is likely to be limited, but is possible. The most likely mechanism for intracellular transfer of Cbl from IF to TCII involves initial lysosomal proteolysis of IF, with subsequent Cbl binding to TCII in a more neutral cellular compartment.

SEPARATION OF FERMENTATION PRODUCTS BY MEMBRANE TECHNIQUES. IV. ELECTRODIALYTIC CONVERSION OF CARBOXYLATES TO CARBOXYLIC ACIDS

For the salt-to-acid conversion of carboxylates by ED technique, the high resistance of weak carboxylic acid solutions limits a current and increases the energy consumption per unit of a product. Carrying experiments for the conversion of sodium lactate to lactic acid (pKlactic = 3.86), we proved that the energy consumption can be lowered by filling the acid compartment in ED unit with the hydrogen conducting filler. In this paper the results of the same procedure applied for the conversion of sodium acetate to acetic acid (pKacetic = 4.75) and sodium propionate to propionic acid (pKpropionic = 4.87) are presented. It has been stated that with a filler in a unit the limiting current densities increase from 0.9 mA/cm2 to 19.5 mA/cm2 for the production of acetic acid and from 0.75 mA/cm2 to 22 mA/cm2 for propionic acid. With these current densities, the intensification factor found for these two conversions was within 30–35, and the energy consumption was in a range 0.3–0.5 kWh/mol. Two phenomena coupled to electrotransport—osmotic dilution and back diffusion of acids—are known to depress the yield of conversion. By experiments performed for acetic, propionic, and lactic acids using three anion exchange membranes Neosepta AM-1, ACM, and AMX (Tokuyama Co., Japan) it has been stated that diffusional leakage of acetic acid is rather high (up to 1 mol/m2h), whereas for lactic acid it is much lower (˜0.1 mol/m2h). Of three membranes tested, the Neosepta AMX was the most effective in preventing both effects, thus assisting in getting high-yield conversions.

Conversion of sodium lactate to lactic acid with water-splitting electrodialysis.

The conversion of sodium lactate to lactic acid with water-splitting electrodialysis was investigated. One way of reducing the power consumption is to add a conductive layer to the acid compartment. Doing this reduced the power consumption by almost 50% in a two-compartment cell, whereas the electric current efficiency was not affected at all. Three different solutions were treated in the electrodialysis unit: a model solution with 70 g/L of sodium lactate and a fermentation broth that had been prefiltered two different ways. The fermentation broth was either filtered in an open ultrafiltration membrane (cut-off of 100,000 Dalton) in order to remove the microorganisms or first filtered in the open ultrafiltration membrane and then in an ultrafiltration membrane with a cut-off of 2000 Dalton to remove most of the proteins. The concentration of sodium lactate in the fermentation broth was 70 g/L, as well. Organic molecules present in the broth (peptides and similar organic material) fouled the membranes and, therefore, increased power consumption. Power consumption increased more when permeate from the more open ultrafiltration membrane was treated in the electrodialysis unit than when permeate from the membrane with the lower cut-off was treated, since there was a higher amount of foulants in the former permeate. However, the electrodialysis membranes could be cleaned efficiently with a 0.1 M sodium hydroxide solution.

Fusion protein toxins based on diphtheria toxin: Selective targeting of growth factor receptors of eukaryotic cells

Publisher Summary The construction of diphtheria toxin-based fusion protein toxins provides a means for the selective targeting and elimination of eukaryotic cells that express on their surface the targeted receptor. When bound to their respective cell surface receptors, the diphtheria toxin-based fusion protein toxins are internalized into the cell by receptor-mediated endocytosis. Productive delivery of the catalytic domain to the target cell cytosol requires passage through an acidic early endosomal compartment. As the lumen of the early endosome becomes acidified through the action of a vATPase, the transmembrane domain of the fusion protein spontaneously denatures and forms a pore, or channel, in the endosomal membrane and facilitates the translocation of the catalytic domain to the cytosol of the target cell. Because passage through an acid compartment is an essential step in the intoxication process, prior knowledge that a given surrogate ligand is internalized in an early endosomal compartment that becomes acidified is important.

Regulation of Intracellular Iron Metabolism in Human Erythroid Precursors by Internalized Extracellular Ferritin

Human erythroid precursors grown in culture possess membrane receptors that bind and internalize acid isoferritin. These receptors are regulated by the iron status of the cell, implying that ferritin iron uptake may represent a normal physiologic pathway. The present studies describe the fate of internalized ferritin, the mechanisms involved in the release of its iron, and the recognition of this iron by the cell. Normal human erythroid precursors were grown in a 2-phase liquid culture that supports the proliferation, differentiation, and maturation of erythroid precursors. At the stage of polychromatic normoblasts, cells were briefly incubated with (59)Fe- and/or (125)I-labeled acid isoferritin and chased. The (125)I-labeled ferritin protein was rapidly degraded and only 50% of the label remained in intact ferritin protein after 3 to 4 hours. In parallel, (59)Fe decreased in ferritin and increased in hemoglobin. Extracellular holoferritin uptake elevated the cellular labile iron pool (LIP) and reduced iron regulatory protein (IRP) activity; this was inhibited by leupeptin or chloroquine. Extracellular apoferritin taken up by the cell functioned as an iron scavenger: it decreased the level of cellular LIP and increased IRP activity. We suggest that the iron from extracellular is metabolized in a similar fashion by developing erythroid cells as is intracellular ferritin. Following its uptake, extracellular ferritin iron is released by proteolytic degradation of the protein shell in an acid compartment. The released iron induces an increase in the cellular LIP and participates in heme synthesis and in intracellular iron regulatory pathways.

Regulation of Intracellular Iron Metabolism in Human Erythroid Precursors by Internalized Extracellular Ferritin

AbstractHuman erythroid precursors grown in culture possess membrane receptors that bind and internalize acid isoferritin. These receptors are regulated by the iron status of the cell, implying that ferritin iron uptake may represent a normal physiologic pathway. The present studies describe the fate of internalized ferritin, the mechanisms involved in the release of its iron, and the recognition of this iron by the cell. Normal human erythroid precursors were grown in a 2-phase liquid culture that supports the proliferation, differentiation, and maturation of erythroid precursors. At the stage of polychromatic normoblasts, cells were briefly incubated with 59Fe- and/or125I-labeled acid isoferritin and chased. The125I-labeled ferritin protein was rapidly degraded and only 50% of the label remained in intact ferritin protein after 3 to 4 hours. In parallel, 59Fe decreased in ferritin and increased in hemoglobin. Extracellular holoferritin uptake elevated the cellular labile iron pool (LIP) and reduced iron regulatory protein (IRP) activity; this was inhibited by leupeptin or chloroquine. Extracellular apoferritin taken up by the cell functioned as an iron scavenger: it decreased the level of cellular LIP and increased IRP activity. We suggest that the iron from extracellular is metabolized in a similar fashion by developing erythroid cells as is intracellular ferritin. Following its uptake, extracellular ferritin iron is released by proteolytic degradation of the protein shell in an acid compartment. The released iron induces an increase in the cellular LIP and participates in heme synthesis and in intracellular iron regulatory pathways.

Regional variation in small intestinal (SI) mucosal protein synthesis and the effect of colectomy on whole-body protein turnover

AIM: We have measured protein synthesis in the SI mucosa to assess possible differences in the rates of mucosal protein synthesis between the proximal and distal regions of the SI in ileostomates and to assess the effect of colectomy on protein turnover. METHODS: Six subjects with ileostomy were studied (mean _+ SD) (46 _+ 21y, 65 _+ 14kg, 169 + 6cm) and the results compared with 8 normal volunteer subjects (44_+15y, 71_+ 12kg, 171 _+ 1 lcm). The ileostomy in these subjects allowed practical access to the distal region of the SI. The terminal ileum was histologically normal in all ileostomy subjects studied. All subjects received primed, continuous IV infusions of L-[1-13C] leucine after an overnight fast. After 4h of tracer infusion jejunal and ileal biopsies were obtained. RESULTS: The results are presented as means _+ SD. Rates of jejunal and ileal mucosal protein synthesis were 2.14 _+ 0.2 and 1.2 + 0.2 (%h -l) respectively; jejunal vs. ileal p<0.001. The whole-body protein turnover rate was, ileostomates vs controls; 145 _+ 15vs. 196 + 44umol/kg/h, p<0.01. In the SI mucosa of subjects with ileostomy the rates of protein synthesis were different at different levels, being significantly higher at the proximal level and lower at the distal level. The plasma leucine enrichment increased by 28% and plasma ketoisocaproate enrichment by 26% with a significantly reduced whole-body protein turnover. CONCLUSION: These changes are probably related to the reduction in the size of the plasma amino acid compartment or reduced lean tissue mass following colectomy and indicate that the colon has a significant contribution to the whole-body protein turnover.