INRA de Clermont-Fd/Theix, UMR 1019, Unité de Nutrition Humaine, 63000, Clermont-Ferrand, France.
Amino Acids. 2011 Feb;40(2):543-52. doi: 10.1007/s00726-010-0672-6. Epub 2010 Jul 1.
Cysteine is considered as a conditionally indispensable amino acid. Its dietary supply should thus be increased when endogenous synthesis cannot meet metabolic need, such as during inflammatory diseases. However, studies in animal models suggest a high first-pass extraction of dietary cysteine by the intestine, limiting the interest for an oral supplementation. We investigated here unidirectional fluxes of cysteine across the portal-drained viscera (PDV) of multi-catheterized minipigs, using simultaneous intragastric L-[(15)N] cysteine and intravenous L-[3,3D2] cysteine continuous infusions. We showed that in minipigs fed with an elemental enteral solution, cysteine first-pass extraction by the intestine is about 60% of the dietary supply, and that the PDV does not capture arterial cysteine. Beside dietary cysteine, the PDV release non-dietary cysteine (20% of the total cysteine release), which originates either from tissue metabolism or from reabsorption of endogenous secretion, such as glutathione (GSH) biliary excretion. Experimental ileitis induced by local administration of trinitrobenzene sulfonic acid, increased liver and ileal GSH fractional synthesis rate during the acute phase of inflammation, and increased whole body flux of cysteine. However, cysteine uptake and release by the PDV were not affected by ileitis, suggesting an adaptation of the intestinal sulfur amino acid metabolism in order to cover the additional requirement of cysteine linked to the increased GSH synthesis. We conclude that the small intestine sequesters large amounts of dietary cysteine during absorption, limiting its release into the bloodstream, and that the other tissues of the PDV (colon, stomach, pancreas, spleen) preferentially use circulating methionine or cysteine-containing peptides to cover their cysteine requirement.
半胱氨酸被认为是条件必需氨基酸。因此，当内源性合成不能满足代谢需求时，如在炎症性疾病期间，应该增加其膳食供应。然而，动物模型研究表明，肠道对半胱氨酸的初次通过提取率很高，限制了口服补充的兴趣。我们在这里使用胃内连续 L-[(15)N]半胱氨酸和静脉内 L-[3,3D2]半胱氨酸连续输注，研究了多导管小型猪门静脉引流内脏（PDV）中半胱氨酸的单向通量。我们表明，在接受元素肠内溶液喂养的小型猪中，肠道对半胱氨酸的初次通过提取约占膳食供应的 60%，并且 PDV 不捕获动脉半胱氨酸。除了膳食半胱氨酸外，PDV 还释放非膳食半胱氨酸（总半胱氨酸释放量的 20%），其来源于组织代谢或内源性分泌物（如谷胱甘肽[GSH]胆汁排泄）的再吸收。局部给予三硝基苯磺酸诱导实验性回肠炎会增加炎症急性期肝脏和回肠 GSH 部分合成率，并增加全身半胱氨酸通量。然而，PDV 对半胱氨酸的摄取和释放不受回肠炎影响，表明肠道硫氨基酸代谢的适应性变化，以满足与增加 GSH 合成相关的额外半胱氨酸需求。我们得出结论，小肠在吸收过程中会摄取大量膳食半胱氨酸，限制其释放到血液中，而 PDV 的其他组织（结肠、胃、胰腺、脾脏）则优先使用循环蛋氨酸或含半胱氨酸的肽来满足其半胱氨酸需求。
