Transport of tricarballylate by intestinal brush‐border membrane vesicles from steers

Wolffram, Siegfried; Zimmermann, W; Scharrer, E.

doi:10.1113/expphysiol.1993.sp003699

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…With respect to Na+ and pH dependence as well as substrate specificity the colonic transport mechanism for tri-and dicarboxylates described in this study closely resembles the respective carriers, located in the brush-border membrane of the small intestine (Browne et al 1978;Wolffram et al 1990Wolffram et al , 1992Wolffram et al , 1993 and the proximal tubules of the kidney (Kippen, Hirayama, Klinenberg & Wright, 1979;Wright, Kippen, Klinenberg & Wright, 1980;Wright, Kippen & Wright, 1982b;Grassl, Heinz & Kinne, 1983;Jorgensen, Kragh-Hansen, Roigaard-Petersen & Sheick, 1983;Barac-Nieto, 1984;Wright, 1985). In experiments using isolated brush-border membrane vesicles from renal cortex (Wright et al 1982a) or small intestine ) a strong inhibitory effect of Li' on Na+dependent uptake of Krebs cycle intermediates has been demonstrated.…”

Section: Discussionsupporting

confidence: 64%

“…citrate or succinate, from the small intestine has been investigated in various species (Browne, Sandford & Smyth, 1978; Wolffram, Bisang, Grenacher & Scharrer, 1990; Wolffram, Hagemann, Grenacher & Scharrer, 1992; Wolffram, Zimmermann & Scharrer, 1993) no information on a possible absorption of succinate by the large intestine has been available until now. Uptake of triand dicarboxylates across the brush-border membrane of the epithelium of the small intestine involves a Na+-dependent carrier-mediated process which is qualitatively similar to the carrier for the reabsorption of Krebs cycle intermediates in the proximal tubules of the kidney (Wolffram et al 1990(Wolffram et al , 1993. In contrast to the small intestine, cotransport of organic substrates and Na+ ions appears to be essentially absent in the large intestine of adult mammals (Parsons & Paterson, 1965;Binder, 1970).…”

Section: Introductionmentioning

confidence: 99%

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Carrier‐mediated transport is involved in mucosal succinate uptake by rat large intestine

Wolffram

Badertscher²,

Scharrer³

1994

Experimental Physiology

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SUMMARYMucosal uptake of succinate across the luminal epithelial border in various segments of the large intestine of the rat (proximal and distal colon, caecum) was investigated using an in vitro mucosal uptake technique. For comparison, some experiments with jejunal preparations were also performed. Additionally, disappearance of succinate from the lumen of ligated loops of the proximal and distal colon was measured in vivo. In the ligated loop experiments, the succinate concentration of the instilled solution significantly decreased during a period of 30 min in both colonic segments, indicating absorption of succinate. The in vitro experiments revealed a distinct Na+ dependence of mucosal succinate uptake in all intestinal segments investigated. Because succinate uptake by the colonic mucosa of germ-free rats was similarly enhanced in the presence of Na+ compared with Na+-free conditions, measured uptake appears to be due to mucosal uptake rather than to Na+-dependent uptake of succinate by bacteria associated with the mucosa. The evaluation of the kinetics of succinate transport in the proximal colon and jejunum, respectively, revealed a single, Na+-dependent saturable component and a diffusive component in both intestinal segments. With respect to the apparent kinetic parameters of the carrier-mediated transport component, the transport capacity (Vmax) of the jejunal carrier appears to be substantially higher compared with the colonic mechanism (80 and 11 nmol cm-2 (5 min)-', respectively) whereas the affinity constants (K.) did not differ markedly in both segments (0 67 and 0 41 mmol 1-1, respectively). Mucosal uptake of 14C-labelled succinate in the proximal colon was inhibited by unlabelled succinate, fumarate, citrate and tricarballylate, but not by glutamate, L-leucine or butyrate. Na+-dependent uptake of the tricarboxylate tricarballylate but not of the dicarboxylate succinate was significantly enhanced by lowering the pH from 7-0 to 5 5, indicating preferential transport of the protonated forms of tricarboxylates. It is concluded from the present results that a Na+-dependent, saturable carrier is involved in the uptake of structurally related tri-and dicarboxylates by the colonic mucosa of the rat.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Carrier‐mediated transport is involved in mucosal succinate uptake by rat large intestine

Wolffram

Badertscher²,

Scharrer³

1994

Experimental Physiology

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“…The mechanisms underlying the shift in tricarballylic acid post-OGTT plasma excursion upon improvement in metabolic health remain to be evaluated experimentally, but changes in gut tricarballylic acid production concomitant with altered microbial ecology may have occurred. Tricarballylic acid uptake transporters in the gut brush border, described as a Na + -dependent transporter shared with citrate, have been described for cattle [55] and likely played a role in glucose-responsive uptake of this organic acid in our human cohort. It remains to be seen if changes in blood levels of tricarballylic acid impact human host biology, but in an extreme example, rumen over-production of tricarballylic acid in cattle eating grasses high in trans-aconitate is implicated in inhibition of host tissue aconitase thought to contribute to grass tetany [52], [53].…”

Section: Discussionmentioning

confidence: 78%

Improved Metabolic Health Alters Host Metabolism in Parallel with Changes in Systemic Xeno-Metabolites of Gut Origin

et al. 2014

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Novel plasma metabolite patterns reflective of improved metabolic health (insulin sensitivity, fitness, reduced body weight) were identified before and after a 14–17 wk weight loss and exercise intervention in sedentary, obese insulin-resistant women. To control for potential confounding effects of diet- or microbiome-derived molecules on the systemic metabolome, sampling was during a tightly-controlled feeding test week paradigm. Pairwise and multivariate analysis revealed intervention- and insulin-sensitivity associated: (1) Changes in plasma xeno-metabolites (“non-self” metabolites of dietary or gut microbial origin) following an oral glucose tolerance test (e.g. higher post-OGTT propane-1,2,3-tricarboxylate [tricarballylic acid]) or in the overnight-fasted state (e.g., lower γ-tocopherol); (2) Increased indices of saturated very long chain fatty acid elongation capacity; (3) Increased post-OGTT α-ketoglutaric acid (α-KG), fasting α-KG inversely correlated with Matsuda index, and altered patterns of malate, pyruvate and glutamine hypothesized to stem from improved mitochondrial efficiency and more robust oxidation of glucose. The results support a working model in which improved metabolic health modifies host metabolism in parallel with altering systemic exposure to xeno-metabolites. This highlights that interpretations regarding the origins of peripheral blood or urinary “signatures” of insulin resistance and metabolic health must consider the potentially important contribution of gut-derived metabolites toward the host's metabolome.

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“…To get a better insight into the discrimination between isocitrate and citrate on marker gene expression, the effect of feeding the nonmetabolizable citrate analog tricarballylate (Wolffram et al, 1993) was also tested. Tricarballylate can be transported into cells and mitochondria via citrate transporters.…”

Section: Tricarballylate Feeding Resembles the Citrate Response Of Mamentioning

confidence: 99%

Transcriptomic Analysis of the Role of Carboxylic Acids in Metabolite Signaling in Arabidopsis Leaves

et al. 2013

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The transcriptional response to metabolites is an important mechanism by which plants integrate information about cellular energy and nutrient status. Although some carboxylic acids have been implicated in the regulation of gene expression for select transcripts, it is unclear whether all carboxylic acids have the same effect, how many transcripts are affected, and how carboxylic acid signaling is integrated with other metabolite signals. In this study, we demonstrate that perturbations in cellular concentrations of citrate, and to a lesser extent malate, have a major impact on nucleus-encoded transcript abundance. Functional categories of transcripts that were targeted by both organic acids included photosynthesis, cell wall, biotic stress, and protein synthesis. Specific functional categories that were only regulated by citrate included tricarboxylic acid cycle, nitrogen metabolism, sulfur metabolism, and DNA synthesis. Further quantitative real-time polymerase chain reaction analysis of specific citrate-responsive transcripts demonstrated that the transcript response to citrate is time and concentration dependent and distinct from other organic acids and sugars. Feeding of isocitrate as well as the nonmetabolizable citrate analog tricarballylate revealed that the abundance of selected marker transcripts is responsive to citrate and not downstream metabolites. Interestingly, the transcriptome response to citrate feeding was most similar to those observed after biotic stress treatments and the gibberellin biosynthesis inhibitor paclobutrazol. Feeding of citrate to mutants with defects in plant hormone signaling pathways did not completely abolish the transcript response but hinted at a link with jasmonic acid and gibberellin signaling pathways. Our results suggest that changes in carboxylic acid abundances can be perceived and signaled in Arabidopsis (Arabidopsis thaliana) by as yet unknown signaling pathways.

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Transport of tricarballylate by intestinal brush‐border membrane vesicles from steers

Cited by 6 publications

References 26 publications

Carrier‐mediated transport is involved in mucosal succinate uptake by rat large intestine

Carrier‐mediated transport is involved in mucosal succinate uptake by rat large intestine

Improved Metabolic Health Alters Host Metabolism in Parallel with Changes in Systemic Xeno-Metabolites of Gut Origin

Transcriptomic Analysis of the Role of Carboxylic Acids in Metabolite Signaling in Arabidopsis Leaves

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