Belloiu D D
C. I. Parhon Institute of Endocrinology, Bucharest, Romania.
Endocrinologie. 1990 Jan-Mar;28(1):3-13.
This theoretic study deals with some biochemical considerations 1) of a general nature, on cellular regulation both by the messenger systems: type A and type C (MS-A & MS-C) and by the allosteric system, and 2) of a special nature, taking into account, for example, the antagonism between the catabolic oxidation of free fatty acids (FFA) and anabolic aerobic glycolysis, as a major mechanism of allosteric short-term regulation of glycemic homeostasis. The discussion at molecular level is facilitated by presentation of a detailed scheme of a didactic and integrative character which consists not only of an original and rational assamblage of the main anabolic and catabolic pathways of the intermediary glucidolipidic metabolism in the liver ("chemical anatomy") but also of the messengerial and allosteric regulation of these pathways ("chemical physiology"). The author also presents a second scheme, more stylized and resumative which seems to show more clearly the antagonism between hepatic oxidation of FFA (expressing the catabolic phase) and aerobic glycolysis (expressing the anabolic phase); this may partly explain why the two phases cannot be simultaneously but only alternatively functional. Hepatic catabolic hyper-oxidation of FFA inhibits anabolic aerobic glycolysis not only at cytosolic level (the negative allo-effectors: 1) FA-CoA on malonyl-CoA synthesis and even 2) citrate, derived from FFA, on PFK-1), but also, particularly, at mitochondrial level, i.e., the negative allo-effector Ac-CoA, derived from FFA, on pyruvic dehydrogenase. On the other hand, aerobic glycolysis inhibits FFA oxidation through the negative allo-effector malonyl-CoA on CAT-1. As a confirmation of these notions, the author cites some clinical evidence such as: the hyperglycemic phenomenon (Randle) produced by an excess of FFA oxidation, the hypoglycemic effect (Reaven) by administration of Etomoxir (an inhibitor of FFA oxidation) and the clinical hypoglycemic and hypoketotic syndrome (Nyhan) produced by a genetical defect in FFA oxidation. Clearly, it must be emphasized that both allosteric regulation and messengerial regulation are of clinical value, considering that "our knowledge of regulation and control is still relatively primitive" (Nossal).
1）具有一般性，涉及信使系统（A 型和 C 型信使系统，即 MS - A 和 MS - C）以及变构系统对细胞的调节；2）具有特殊性，例如考虑游离脂肪酸（FFA）的分解代谢氧化与合成代谢有氧糖酵解之间的拮抗作用，这是血糖稳态变构短期调节的主要机制。通过展示一个详细的、具有教学和综合性质的方案，便于在分子水平上进行讨论。该方案不仅包括肝脏中糖脂中间代谢主要合成代谢和分解代谢途径的原始且合理的组合（“化学解剖”），还包括这些途径的信使调节和变构调节（“化学生理学”）。作者还展示了第二个更具程式化和概括性的方案，它似乎更清楚地显示了 FFA 的肝脏氧化（代表分解代谢阶段）与有氧糖酵解（代表合成代谢阶段）之间的拮抗作用；这可能部分解释了为什么这两个阶段不能同时发挥作用，而只能交替发挥作用。FFA 的肝脏分解代谢过度氧化不仅在细胞质水平抑制合成代谢有氧糖酵解（负变构效应物：1）FA - CoA 对丙二酰 - CoA 合成的抑制，甚至 2）源自 FFA 的柠檬酸对磷酸果糖激酶 - 1 的抑制），而且特别在线粒体水平，即源自 FFA 的负变构效应物乙酰 - CoA 对丙酮酸脱氢酶的抑制。另一方面，有氧糖酵解通过丙二酰 - CoA 对 CAT - 1 的负变构效应来抑制 FFA 氧化。作为这些观点的佐证，作者引用了一些临床证据，如：FFA 氧化过量产生的高血糖现象（兰德尔现象）、给予依托莫西（一种 FFA 氧化抑制剂）产生的低血糖效应（雷文效应）以及 FFA 氧化遗传缺陷导致的临床低血糖和低酮血症综合征（尼汉综合征）。显然，必须强调的是，考虑到“我们对调节和控制的认识仍然相对原始”（诺萨尔），变构调节和信使调节都具有临床价值。
