Enzymes involved in l-carnitine biosynthesis are expressed by small intestinal enterocytes in mice: Implications for gut health Prem S. Shekhawat, Srinivas.

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Presentation transcript:

Enzymes involved in l-carnitine biosynthesis are expressed by small intestinal enterocytes in mice: Implications for gut health Prem S. Shekhawat, Srinivas Sonne, A. Lee Carter, Dietrich Matern, Vadivel Ganapathy Journal of Crohn's and Colitis Volume 7, Issue 6, Pages e197-e205 (July 2013) DOI: 10.1016/j.crohns.2012.08.011 Copyright © 2012 European Crohn's and Colitis Organisation Terms and Conditions

Figure 1 Pathway of de novo l-carnitine biosynthesis. Carnitine is biosynthesized from TML following its release from proteins by degradation. TML is hydroxylated by TMLD resulting in production of HTML, which is further cleaved to TMABA by an aldolase in the presence of pyridoxal 5′-phosphate. Subsequently, TMABA is oxidized to γ-BBH by TMABA-DH and in the final step γ-BBH is hydroxylated to carnitine by γ-BBH. Journal of Crohn's and Colitis 2013 7, e197-e205DOI: (10.1016/j.crohns.2012.08.011) Copyright © 2012 European Crohn's and Colitis Organisation Terms and Conditions

Figure 2 Expression of enzymes involved in carnitine biosynthesis in mice. A composite image of real-time-PCR experiments showing relative mRNA expression levels specific for TMLD, TMABADH, SHMT1, SHMT2 and γ-BBH in small intestine, liver, kidney, and skeletal muscle in relation to expression of HPRT. Journal of Crohn's and Colitis 2013 7, e197-e205DOI: (10.1016/j.crohns.2012.08.011) Copyright © 2012 European Crohn's and Colitis Organisation Terms and Conditions

Figure 3 γ-Butyrobetaine hydroxylase (γ-BBH) activity in mouse small intestine. Gut scrapings from mouse small intestine had γ-BBH activity of 9.7±3.5pmol/mg/min, in comparison to that of liver 22.7±7.6pmol/mg/min. Journal of Crohn's and Colitis 2013 7, e197-e205DOI: (10.1016/j.crohns.2012.08.011) Copyright © 2012 European Crohn's and Colitis Organisation Terms and Conditions

Figure 4 High-resolution image (×20) of in situ hybridization for γ-BBH expression in mouse jejunum. Composite image of γ-BBH expression in jejunum; panel A is hybridized with an antisense probe and panel B with a sense probe. Panel A shows dark staining localized mainly to surface epithelial cells (bar represents 50μm). Journal of Crohn's and Colitis 2013 7, e197-e205DOI: (10.1016/j.crohns.2012.08.011) Copyright © 2012 European Crohn's and Colitis Organisation Terms and Conditions

Figure 5 High-resolution image (×20) of in situ hybridization for γ-BBH in mouse ileum. Composite image to show localization of γ-BBH expression; panel A is hybridized with an antisense probe and panel B with a sense probe. γ-BBH gene expression was seen mainly in the surface epithelial cells of villous structure with faint staining in the crypts and mesenchymal cells of the villi (bar represents 50μm). Journal of Crohn's and Colitis 2013 7, e197-e205DOI: (10.1016/j.crohns.2012.08.011) Copyright © 2012 European Crohn's and Colitis Organisation Terms and Conditions

Figure 6 High-resolution image (×20) of in situ hybridization for γ-BBH in mouse colon. Composite image to show localization of γ-BBH expression; panel A is hybridized with an antisense probe and panel B with a sense probe. γ-BBH gene expression was seen mainly in the surface epithelial cells of with very faint staining of mesenchymal mucus producing cells (bar represents 50μm). Journal of Crohn's and Colitis 2013 7, e197-e205DOI: (10.1016/j.crohns.2012.08.011) Copyright © 2012 European Crohn's and Colitis Organisation Terms and Conditions