Zs-Nagy I
Department of Gerontology (VILEG Hungarian Section), University of Debrecen, Medical Faculty, PO Box 50, Debrecen, H-4012, Hungary.
Mech Ageing Dev. 2001 Jun;122(8):811-21. doi: 10.1016/s0047-6374(01)00237-8.
The paper of Kitani cited in the title has raised an apparent contradiction regarding the validity of certain aspects of the membrane hypothesis of aging (MHA). He collected data showing that a number of detoxifying liver enzyme activities, although decline with age in male Fischer 344 rats, remain at an unchanged level in females of the same strain. He concluded that the main assumption of the MHA, according to which intracellular enzyme activities generally decline with age, cannot be maintained, and invoked me (p. 312) 'ellipsis to provide in the future ample (and convincing) evidence' in this respect. The present paper answers this criticism by showing that the apparent contradiction mentioned above is based on a misunderstanding on behalf of Kitani. Namely, MHA speaks about the general, density-dependent decline of the catalytic rate constant of any enzyme (k(cat)), i.e., activity per mole of enzyme, being the true specific activity of the enzymes. This parameter inevitably decreases at the increased physical density of the intracellular colloids during aging. This statement derives from the molecular enzyme kinetic models, and has extensively been proven experimentally, too. On the other hand, Kitani speaks about enzyme activities per mg total protein content of certain tissue extracts, which is a very illdefined parameter, since the concentration of the measured enzyme remains unknown. Therefore, this latter parameter is irrelevant from the point of view of MHA in any aspect.
标题中引用的北谷的论文就衰老的膜假说（MHA）某些方面的有效性提出了一个明显的矛盾。他收集的数据表明，一些解毒肝酶活性虽然在雄性费希尔344大鼠中随年龄下降，但在同一品系的雌性大鼠中保持不变。他得出结论，MHA的主要假设，即细胞内酶活性通常随年龄下降，不能成立，并援引我（第312页）“省略号”来在这方面“提供未来充分（且有说服力）的证据”。本文通过表明上述明显的矛盾是基于北谷的误解来回应这一批评。也就是说，MHA讨论的是任何酶的催化速率常数（k(cat)）的普遍的、密度依赖性下降，即每摩尔酶的活性，这是酶的真正比活性。在衰老过程中，随着细胞内胶体物理密度的增加，这个参数不可避免地会下降。这个说法源于分子酶动力学模型，并且也已得到广泛的实验证明。另一方面，北谷讨论的是某些组织提取物每毫克总蛋白含量的酶活性，这是一个非常不明确的参数，因为所测酶的浓度仍然未知。因此，从MHA的角度来看，后一个参数在任何方面都是不相关的。
