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发育和营养状态对啮齿动物小肠摄取、代谢及游离和乙酰-L-肉碱释放的影响。

Effect of development and nutritional state on the uptake, metabolism and release of free and acetyl-L-carnitine by the rodent small intestine.

作者信息

Gross C J, Savaiano D A

机构信息

Department of Biochemistry, University of Minnesota, St. Paul 55108.

出版信息

Biochim Biophys Acta. 1993 Nov 3;1170(3):265-74. doi: 10.1016/0005-2760(93)90009-x.

Abstract

Intestinal carnitine levels and the incorporation and release of exogenous, [14C]carnitine were compared in intestine from adult rat and guinea pig. Total carnitine levels were 4-fold higher in rat as compared to guinea pig intestine. Retention of label was also 4-fold greater, 4 h after placing carnitine (7 nmol) in the lumen. Carnitine was detected in rat chow (64 nmol/g) but not in guinea pig chow. Intestinal carnitine was reduced 2-fold in rats fed a carnitine-free diet for 2 weeks, suggesting the importance of dietary carnitine in determining intestinal carnitine levels. Two conditions where fatty acid oxidation is increased (fasting and suckling) resulted in elevated carnitine levels and retention. In the 3-day fasted guinea pig, intestinal carnitine increased by 40% and retention of a lumenal dose of [14C]carnitine increased about 7-fold after 4 h. During suckling, carnitine levels peaked after 3 days (792 nmol/g) and decreased to near adult levels after 7 days (108 nmol/g). Retention of a lumenal dose of carnitine was greater after 4 h in 1-day old neonatal, than in adult intestine (82% vs. 7% of a 7 nmol dose, respectively). This reflects, in part, the larger intestinal carnitine pool on day 1 (352 nmol/g) than on day 29 (91 nmol/g). The calculated efflux of total intestinal carnitine after 4 h was similar for adults and neonates (72 vs. 58 nmol/g) suggesting that efflux relative to pool size was greater in the adult than in the neonate. Uptake of [14C]acetylcarnitine was similar to [14C]carnitine in 1-day old animals, but was retained to a lesser extent (36% vs. 82%, respectively) after 4 h. The calculated efflux of total intestinal carnitine when acetylcarnitine was the substrate was about 4-fold that when carnitine was the substrate. Incorporation of [14C]carnitine into enterocytes isolated from 3-day old animals was 4-fold greater than into enterocytes isolated from adults (152 vs. 36 pmol/mg protein after 60 min). Active transport of carnitine into enterocytes from neonates, but not from adults is suggested, since labeled free intracellular carnitine reached 4-fold the calculated equilibrium value in neonatal enterocytes, but did not exceed the equilibrium value in adult enterocytes.

摘要

比较了成年大鼠和豚鼠肠道中的肉碱水平以及外源性[14C]肉碱的掺入和释放情况。大鼠肠道中的总肉碱水平比豚鼠肠道高4倍。在肠腔中放置肉碱(7 nmol)4小时后,标记物的保留量也高4倍。在大鼠饲料中检测到肉碱(64 nmol/g),但豚鼠饲料中未检测到。给大鼠喂食不含肉碱的饲料2周后,肠道肉碱水平降低了2倍,这表明膳食肉碱对确定肠道肉碱水平很重要。脂肪酸氧化增加的两种情况(禁食和哺乳)导致肉碱水平和保留量升高。在禁食3天的豚鼠中,肠道肉碱增加了40%,肠腔剂量的[14C]肉碱在4小时后的保留量增加了约7倍。在哺乳期间,肉碱水平在3天后达到峰值(792 nmol/g),7天后降至接近成年水平(108 nmol/g)。1日龄新生儿在4小时后对肠腔剂量肉碱的保留量比成年肠道更大(分别为7 nmol剂量的82%和7%)。这部分反映了第1天(352 nmol/g)比第29天(91 nmol/g)的肠道肉碱池更大。计算得出,4小时后成年和新生儿肠道总肉碱的流出量相似(分别为72和58 nmol/g),这表明相对于池大小,成年动物的流出量比新生儿更大。在1日龄动物中,[14C]乙酰肉碱的摄取与[14C]肉碱相似,但4小时后保留程度较低(分别为36%和82%)。以乙酰肉碱为底物时,计算得出的肠道总肉碱流出量约是以肉碱为底物时的4倍。从3日龄动物分离的肠细胞中[14C]肉碱的掺入量比从成年动物分离的肠细胞高4倍(60分钟后分别为152和36 pmol/mg蛋白质)。由于标记的游离细胞内肉碱在新生儿肠细胞中达到计算平衡值的4倍,但未超过成年肠细胞中的平衡值,提示存在从新生儿而非成年动物的肠细胞向肠细胞的肉碱主动转运。

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