Galton D J, Higgins M J, Reckless J P
Lancet. 1975 May 31;1(7918):1224-6. doi: 10.1016/s0140-6736(75)92200-x.
It is postulated that errors in metabolic regulation occur when aminoacid subsitutions or conformational changes occur at allosteric sites on proteins. The cell thus contains its full complement of enzymes, carrier proteins, and receptors, but these proteins do not respond normally to microenvironmental agents such as hormones or activator or inhibitor metabolites. Regulatory errors differ from the classical inborn errors in a number of respects: they can be acquired as well as inherited, when due to defects at allosteric inhibitory sites they lead to loss of regulation of metabolic pathways with oversynthesis of metabolic products without gross accumulation of abnormal intermediates, and they can be treated, in principle, by enzyme inhibitors rather than by enzyme replacement, as for inborn errors.
据推测,当蛋白质的别构位点发生氨基酸取代或构象变化时,就会出现代谢调节错误。因此,细胞含有其完整的酶、载体蛋白和受体,但这些蛋白质对激素、激活剂或抑制剂代谢物等微环境因子不能正常作出反应。调节错误在许多方面与经典的先天性代谢缺陷不同:它们既可以遗传也可以后天获得,当由于别构抑制位点的缺陷导致代谢途径调节丧失,代谢产物过度合成,而没有异常中间体的大量积累时,原则上可以用酶抑制剂治疗,而不像先天性代谢缺陷那样用酶替代治疗。