Marcoullis G, Parmentier Y, Nicolas J P, Jimenez M, Gerard P
J Clin Invest. 1980 Sep;66(3):430-40. doi: 10.1172/JCI109873.
In vivo studies demonstrate that the pancreatic enzymes and the ionic environment in the upper gastrointestinal tract are essential determining factors for transport and absorption of cobalamin in man. Jejunal fluid was aspirated from healthy human volunteers after administration of cyano[57Co]cobalamin preparations. Immunochemical analysis of the aspirates demonstrated that all isotopic vitamin was transferred to a protein that is identical to the gastric intrinsic factor in terms of molecular mass (57,500), ionic nature (mean pI, 5.09), and reactivity with anti-intrinsic factor sera. However, in the aspirates from patients with exocrine pancreatic dysfunction the vitamin was found to be coupled > 60% to a protein identical to R proteins in terms of molecular mass (125,000), ionic nature (mean pI, 3.51), and reactivity with anti-R protein and anti-intrinsic factor sera. The preferential transfer of cobalamin to R proteins in the patients and to intrinsic factor in healthy subjects was associated, respectively, with low and normal levels of pancreatic enzymes in the intestine and these in turn were paralleled respectively by impaired and normal ileal absorption of cobalamin. These findings confirm the suggestion that the formation of unabsorbable cobalamin complexes may be the reason of impaired vitamin absorption in exocrine pancreatic insufficiency. Observations made with other selected patients demonstrate: (a) that decreased enzyme activity and nondegradation of R proteins may also be due to nonactivation of pancreatic zymogens in an acidic pH of the intestinal juice the vitamin transported to the jejunum couples to intrinsic factor when pancreatic function is normal, and to intrinsic factor and R protein in exocrine pancreatic insufficiency. The observations made with these selected patients may explain why not all patients with exocrine pancreatic insufficiency develop imparied cobalamin absorption, and also why the malabsorption is corrected by the administration of bicarbonate in certain patients.
体内研究表明，胰腺酶和上消化道中的离子环境是人体中钴胺素转运和吸收的重要决定因素。给健康人类志愿者服用氰钴胺[57Co]制剂后，从其体内抽取空肠液。对抽取物进行免疫化学分析表明，所有同位素维生素都转移到了一种蛋白质上，该蛋白质在分子量（57,500）、离子性质（平均pI，5.09）以及与抗内因子血清的反应性方面与胃内因子相同。然而，在患有外分泌性胰腺功能不全患者的抽取物中，发现超过60%的维生素与一种蛋白质结合，该蛋白质在分子量（125,000）、离子性质（平均pI，3.51）以及与抗R蛋白和抗内因子血清的反应性方面与R蛋白相同。患者体内钴胺素优先转移至R蛋白，而健康受试者体内则优先转移至内因子，这分别与肠道中胰腺酶水平低和正常有关，而这又分别与钴胺素回肠吸收受损和正常情况平行。这些发现证实了以下推测：不可吸收的钴胺素复合物的形成可能是外分泌性胰腺功能不全时维生素吸收受损的原因。对其他特定患者的观察表明：（a）酶活性降低和R蛋白不降解也可能是由于肠液酸性pH条件下胰腺酶原未被激活所致。当胰腺功能正常时，转运至空肠的维生素与内因子结合；在外分泌性胰腺功能不全时，则与内因子和R蛋白结合。对这些特定患者的观察结果可以解释为什么并非所有外分泌性胰腺功能不全的患者都会出现钴胺素吸收受损，以及为什么在某些患者中通过给予碳酸氢盐可纠正吸收不良。
