Observations on the mechanism of adaptation to low protein intakes.

Observations on the mechanism of adaptation to low protein intakes.
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低蛋白质摄入适应机制的观察。

DOI:
10.1016/s0140-6736(68)91576-6
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发表时间:
1968
期刊:
影响因子:
168.9
通讯作者:
J. Waterlow
J. Waterlow
中科院分区:
医学1区
文献类型:
--
作者:
J. Waterlow

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1968年10月3日,查尔斯·韦斯特在伦敦的皇家内科医学院发表了演讲。在演讲中,作者概述了在他的指导下,牙买加医学研究理事会热带代谢研究单位所做的大量工作。适应问题对于理解营养问题至关重要。虽然某些营养条件会导致身体崩溃,但必须对与健康相容的不同条件进行广泛的适应。为了区分正常状态的结束和异常状态的开始,我们必须识别出机体试图以牺牲他人为代价来保持恒定的那些特征。一个简化的模型假设存在一个恒定大小的含有代谢氮的单一池;这将通过两条途径--从食物和从身体蛋白质的催化剂--获得氨基酸,并将通过两条途径--失去氨基氮,合成为体内蛋白质和尿排泄。在氮的摄入和排泄之间,在代谢库和身体蛋白质之间存在持续的流动。两种替代假设可以解释减少尿氮,以配合摄入量。在第一种情况下,分解率可能会随着摄入量的下降而下降,从而使进入池中的总氮大大减少,周转率与蛋白质摄入量密切相关。在第二种情况下,分解代谢率可能保持不变,因此进入池中的氮量变化不大;这意味着氨基氮流量的重新分配;蛋白质的合成保持开放,而尿素的排泄几乎是封闭的。短时间的低蛋白质摄入量并没有引起任何降低周转率,虽然尿氮排泄量减少到四分之一和三分之一之间的控制大鼠。使用15 N标记的甘氨酸进行了一项类似的研究,其中6名婴儿接受高蛋白饮食(5.2 g蛋白/kg/天),5名婴儿接受低蛋白饮食(1.2 g/kg/天)。低蛋白质摄入量不会降低蛋白质合成和分解代谢的总体速率;两组儿童的总周转率为5-6克蛋白质/公斤/天--大约是大鼠中发现的周转率的四分之一,是成人估计周转率的2或3倍。这些价值观承担彼此类似的关系,因为这样的基础耗氧量率在大鼠,婴儿和adult.Though总营业额是不变的,大鼠死后分析后,连续输注uC-赖氨酸表明变化的蛋白质合成模式与低蛋白饮食;在肝脏,率保持正常或增加,但在肌肉中,它是显着减少。肌肉似乎减少了对氨基酸的需求,为其他组织留下了更多的可用氨基酸。对营养不良和恢复期儿童的血清白蛋白的研究表明,当蛋白质摄入量减少时,白蛋白的合成率立即下降,随后,经过几天的滞后,catenin的比率下降,通过使用标记的精氨酸,已经表明在正常饮食的大鼠中约50%,在低蛋白饮食的大鼠中约70%,肝脏中释放的氨基酸被重新释放,对大鼠适应性酶变化的研究表明,在低蛋白质饮食中,肝脏中氨基酸活化酶的活性增加,尿素循环酶,即进入肝脏的氨基酸将有更大的机会被纳入蛋白质和更小的机会...
In this, the Charles West lecture, given at the Royal College of Physicians, London, on Oct. 3, 1968, the author outlined much of the work done, under his direction, at the Medical Research Council Tropical Metabolism Research Unit, Jamaica.The question of adaptation is crucial to the understanding of nutritional problems. Although some nutritional conditions lead to breakdown, there must be a wide range of adaptation to different conditions compatible with health. To distinguish between the end of the normal and the beginning of the abnormal, we must identify those characteristics which the body tries to maintain constant at the expense of others.A simplified model assumes that there is a single pool of constant size containing metabolic nitrogen; this will receive amino acids by two routes-from the food and from catabolism of body protein-and will lose amino nitrogen by two routes-synthesis into body protein and urinary excretion. between intake of nitrogen and excretion there is a continual flux between the metabolic pool and body protein. Two alternative hypotheses can explain the reduction of urinary nitrogen to match intake. In the first, the catabolic rate may fall with intake so that the total nitrogen entering the pool is greatly reduced, the turnover rate being closely related to protein intake. In the second, the catabolic rate may remain unchanged so that the amount of nitrogen entering the pool does not change much; this implies a redistribution of the flow of amino nitrogen; the synthesis of protein remains open, while the excretion of urea is almost closed.These hypotheses were tested by measuring the total lysine flux in rats given continuous infusions of14C-lysine. Short periods of low protein intake did not cause any decrease in the turnover rate, although urinary excretion of nitrogen was reduced to between a quarter and a third of that in control rats. A similar study with the use of glycine labelled with15N was made with 6 infants on a high protein diet (5.2 g protein/kg/day) and 5 infants on low protein (1.2 g/kg/day). There was no reduction of the overall rates of protein synthesis and catabolism with low protein intakes; both groups of children had a total turnover of 5-6 g protein/kg/day-about a quarter of that found in rats and 2 or 3 times the estimated turnover in adults. These values bear a similar relationship to each other, as do rates of basal oxygen consumption in rat, infant and adult.Though the total turnover was unchanged, post-mortem analysis of rats following continuous infusion withuC-lysine indicated a change in the pattern of protein synthesis with low protein diets; in the liver, the rate remained normal or increased, but in muscle it was markedly reduced. It appeared that muscle reduced its demands, leaving more available amino acid for other tissues.Studies of serum-albumin in malnourished and recovering children on high and low protein diets showed that, when protein intake was reduced, there was an immediate fall in the rate of albumin synthesis, followed, after a lag of several days, by a fall in the rate of catabolism, with a transfer of albumin from the extravascular to the intravascular pool.With the use of labelled arginine, it has been shown that in rats on a normal diet about 50%, and in those on a low protein diet about 70%, of amino acid liberated in the liver is re-utilized for protein synthesis.Studies of adaptive enzyme changes in rats have shown that on low protein diets there is an increase in the activity of the amino acid activating enzymes in the liver and a decrease in the activity of urea cycle enzymes,i.e. an amino acid entering the liver would have a greater chance of being incorporated into protein and a smaller chance …