Impairment of mitochondrial acetoacetyl CoA thiolase activity in the colonic mucosa of patients with ulcerative colitis

Santhanam, Srikanth; Venkatraman, Aparna; Ramakrishna, B. S.

doi:10.1136/gut.2006.108449

Cited by 60 publications

(47 citation statements)

References 29 publications

(32 reference statements)

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“…This enzyme catalyses the important last step of butyrate oxidation and was shown to be significantly impaired in the colonic mucosal of UC patients. 29 Furthermore, in another study, Thibault et al demonstrated that butyrate oxidation deficiency in intestinal inflammation is a consequence of reduced monocarboxylate transporter MCT1-mediated butyrate uptake by colonocytes. 30 They hypothesized that butyrate oxidation may decline because of reduced intracellular butyrate availability.…”

Section: De Preter Et Almentioning

confidence: 98%

Pouchitis, Similar to Active Ulcerative Colitis, Is Associated with Impaired Butyrate Oxidation by Intestinal Mucosa

Preter

Bulteel

Suenaert

et al. 2009

Inflammatory Bowel Diseases

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Section: De Preter Et Almentioning

confidence: 98%

Pouchitis, Similar to Active Ulcerative Colitis, Is Associated with Impaired Butyrate Oxidation by Intestinal Mucosa

Preter

Bulteel

Suenaert

et al. 2009

Inflammatory Bowel Diseases

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“…66 Moreover, the findings that, in patients with UC, only butyrate (but not glucose or glutamine) oxidation is decreased 58,59 sustain the hypothesis of an alteration of the butyrate oxidation pathway. Recently, Santhanam et al 67 reported that the activity of mitochondrial acetoacetyl CoA thiolase was defective in patients with UC, independently of the severity of the disease and of the extent of inflammation. The authors suggested that this defect was related to the increase of free radical concentrations in the mitochondria of intestinal epithelial cells.…”

Section: Defect In Butyrate Oxidation Pathwaymentioning

confidence: 98%

Butyrate utilization by the colonic mucosa in inflammatory bowel diseases

Thibault

Blachier

Darcy‐Vrillon

et al. 2010

Inflammatory Bowel Diseases

209

151

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The short-chain fatty acid butyrate, which is mainly produced in the lumen of the large intestine by the fermentation of dietary fibers, plays a major role in the physiology of the colonic mucosa. It is also the major energy source for the colonocyte. Numerous studies have reported that butyrate metabolism is impaired in intestinal inflamed mucosa of patients with inflammatory bowel disease (IBD). The data of butyrate oxidation in normal and inflamed colonic tissues depend on several factors, such as the methodology or the models used or the intensity of inflammation. The putative mechanisms involved in butyrate oxidation impairment may include a defect in beta oxidation, luminal compounds interfering with butyrate metabolism, changes in luminal butyrate concentrations or pH, and a defect in butyrate transport. Recent data show that butyrate deficiency results from the reduction of butyrate uptake by the inflamed mucosa through downregulation of the monocarboxylate transporter MCT1. The concomitant induction of the glucose transporter GLUT1 suggests that inflammation could induce a metabolic switch from butyrate to glucose oxidation. Butyrate transport deficiency is expected to have clinical consequences. Particularly, the reduction of the intracellular availability of butyrate in colonocytes may decrease its protective effects toward cancer in IBD patients.

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“…For example the activity of the mitochondrial acetoacetyl-CoA thiolase was found to be reduced by 80% in colon cells of patients suffering from ulcerative colitis because of increased mitochondrial H 2 O 2 levels (Santhanam et al, 2007). Reduced thiolase activity in ulcerative colitis was returned to normal by exposure to reductants (Santhanam et al, 2007). Redox-induced (A) Structure of the active site of the human aldehyde dehydrogenase.…”

Section: Mitochondrial Thiolasesmentioning

confidence: 99%

Thiol switches in mitochondria: operation and physiological relevance

Riemer

Schwarzländer

Conrad

et al. 2015

Biological Chemistry

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Mitochondria are a major source of reactive oxygen species (ROS) in the cell, particularly of superoxide and hydrogen peroxide. A number of dedicated enzymes regulate the conversion and consumption of superoxide and hydrogen peroxide in the intermembrane space and the matrix of mitochondria. Nevertheless, hydrogen peroxide can also interact with many other mitochondrial enzymes, particularly those with reactive cysteine residues, modulating their reactivity in accordance with changes in redox conditions. In this review we will describe the general redox systems in mitochondria of animals, fungi and plants and discuss potential target proteins that were proposed to contain regulatory thiol switches.

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Impairment of mitochondrial acetoacetyl CoA thiolase activity in the colonic mucosa of patients with ulcerative colitis

Abstract: A defect of mitochondrial acetoacetyl CoA thiolase occurs in ulcerative colitis. Increased reactive oxygen species generation in mitochondria of epithelial cells in ulcerative colitis may underlie this defect.

Cited by 60 publications

References 29 publications

Pouchitis, Similar to Active Ulcerative Colitis, Is Associated with Impaired Butyrate Oxidation by Intestinal Mucosa

Pouchitis, Similar to Active Ulcerative Colitis, Is Associated with Impaired Butyrate Oxidation by Intestinal Mucosa

Butyrate utilization by the colonic mucosa in inflammatory bowel diseases

Thiol switches in mitochondria: operation and physiological relevance

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