Biochemical considerations regarding cellular regulation through messenger and allosteric systems. Antagonism between catabolic oxidation of free fatty acids and anabolic aerobic glycolysis in the liver.

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).