学术讨论乐意奉陪 (69769)
Posted by: 桂铭
Date: March 30, 2007 11:38AM

方提到的那篇文献我看过。在那篇文章的导言部分，提到了有人报道过在冈比亚(Gambian)的1.5~17个月的小孩吃进的母奶中，约有2%的 lactoferrin存在于小肠中。还提到有另外一篇1991年发表在美国科学院院报的文章中，明确指出婴儿吸入的母奶当中的lactoferrin，可以以完整的形式出现在尿中，说明lactoferrin的确没有完全被肠道分解破坏而被吸收。

Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):2994-8.

Structurally intact (78-kDa) forms of maternal lactoferrin purified from urine
of preterm infants fed human milk: identification of a trypsin-like proteolytic
cleavage event in vivo that does not result in fragment dissociation.

Hutchens TW, Henry JF, Yip TT.

U.S. Department of Agriculture/Agricultural Research Service Children's
Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030.

Two forms of lactoferrin, an intact lactoferrin and a "nicked" but apparently
intact (i.e., 78-kDa) form, have been isolated from the urine of preterm infants
fed human milk. These two forms of lactoferrin, demonstrated to be entirely of
maternal origin, were copurified using affinity columns of immobilized
single-stranded DNA-agarose. The relative concentrations of the intact
lactoferrin and the "nicked" lactoferrin were determined after denaturation and
separation by reverse-phase HPLC. N-terminal sequence analyses showed that the
intact 78-kDa form had lost two residues from its N terminus. The nicked 78-kDa
form was composed of only two fragments; one fragment was identified as the N
terminus of the N-lobe (residues 3-283). The other fragment started with Ser-284
and included the alpha-helical structures at the C terminus of the N-lobe, as
well as the entire C-lobe. Although no disulfide bonds connect these two
fragments, they were tightly associated in vivo and were not separated in vitro
except under denaturing conditions. Limited in vitro digestion of human milk
lactoferrin with trypsin produced a nicked, but stable (78-kDa), form of
DNA-binding lactoferrin nearly indistinguishable from the isolated urinary
lactoferrin, except for the absence of one additional arginine residue at the N
terminus of the N-lobe. Residues involved in the stable molecular interaction
between fragments were evaluated using data obtained from the high-resolution
crystal structure of hololactoferrin. Two features, entirely within the N-lobe,
account for the lack of fragment dissociation after cleavage at residue 283 in
vivo: an extensive interface at the hinge region behind the iron-binding cleft
and an "anchor" sequence traversing the remainder of the N-lobe at 90 degrees
relative to the fragment interface. These results document the remarkably
limited degradation of absorbed lactoferrin in vivo and suggest that
iron-binding activity, receptor-binding properties, and postulated immune cell
regulatory functions remain intact.

Two large (78-kDa) and nearly indistinguishable forms of
maternal lactoferrin were demonstrated in the urine of preterm
infants fed human milk. Some of the urinary lactoferrin
had resisted almost entirely the proteolysis and degradation
typically associated with digestion, absorption, transport,
and excretion; the remainder of the isolated urinary lactoferrin
appeared to retain an intact tertiary structure despite a
nick deep within the primary sequence.

那么为什么方提到的文献当中，给大鼠口服的lactoferrin却检测不到呢？我仔细看了他们的实验设计，发现他们是先给大鼠饥饿18小时，然后，在灌服lactoferrin20和60分钟，甚至隔夜之后，经门静脉取血做检查。阅读这篇文章应该注意几个问题。1：这是9周龄成年大鼠，代谢速率比人高几倍，饿了18小时，消化力极强。2：他们既然知道lactoferrin在大鼠体内的半衰期只有10分钟，却在20和60分钟甚至隔夜才取血样。应该看5和10分钟的血样。3：他们看到了碘标记的lactoferrin分布到大鼠的全身。4:他们用SDS-PAGE的方法来检测血中碘标记的 lactoferrin，这种方法敏感度有问题，尽管如此，他们看到了碘标记的lactoferrin的区带信号比对照组的强，说明有存在，尽管量很低 4：在同一个实验中，他们看到另一种蛋白ovalbumin可以在血中检测到，说明蛋白可以被直接吸收进血液。

另，方在科普文当中说：
但是只要学过高中生物课程就不难明白，食物中的蛋白质是不可能被
人体直接吸收、利用的。蛋白质是由20种氨基酸按一定的序列组成的，不
同的蛋白质有不同的氨基酸序列，因此有不同的功能。但是食物中的蛋白
质进入消化道后，命运都一样：它们的序列都将被破坏，被蛋白酶消化、
降解成一个个的氨基酸，之后这些氨基酸再被吸收进体内，在基因的指导
下，重新合成各种蛋白质在体内发挥其功能。

道理就在于做为一种蛋白质，它将在消化道中被消化、降解成氨基酸后才能被
人体吸收，

现在他改口了：
送交者: 方舟子 于 2007-03-31, 03:41:35:

回答: “牛奶有害”也是“进口”的 由 eng 于 2007-03-30, 20:22:18:

新生儿由于消化功能不完善，有可能吸收完整的蛋白质，

知识的海洋是浩瀚的，人的所知是有限的。