Effects of Substrate Concentration on Metabolic Activities

The effects of variations of substrate concentration on the velocity of an enzymatic reaction. We may only add that in some cases, variations of substrate or co-substrate concentration [S] can exert important effects on the metabolism by permitting either the synthesis, or on the contrary the degradation of a substance X, or by determining the metabolic pathway in which a substance X will be directed.

Thus, for example — the NAD⁺ concentration (which in fact depends on the oxygen content) is a determinant factor of the fate of pyruvic acid. If O₂ is present in sufficient quantities, the electron transport system will function properly, with the result that NAD⁺ will be present in the cell in sufficient amount to enable pyruvic acid to undergo oxidative decar­boxylation, process during which NAD⁺ is required for reoxidizing the reduced lipoic acid; if on the contrary little oxygen is available, the electron transport system will not permit the reoxidation of NADH to NAD⁺, and in these conditions —pyruvic acid is reduced by NADH + H⁺ to lactic acid (see fig. 4-30).

This clearly shows that oxygen concentration determines whether pyruvic acid is reduced to lactic acid or oxidized to acetyl-coenzyme A which enters the Krebs cycle.

One may also cite as example, the effect of ATP concentration on the synthesis and degradation of glycogen. An increase of ATP concentration favours the formation of UTP, then of UDP-glucose and thereby promotes the synthesis of glycogen; this effect is further enhanced by the fact that a high ATP concentra­tion is established at the cost of ADP and P_i, whose concentrations decrease, which diminishes the degradation of glycogen as it requires P_i (see fig. 4-23); there is therefore an increase of the synthesis of glycogen and a decrease of its degradation.

On the contrary a low concentration of ATP (and consequently, high concentration of ADP + P_i) is unfavourable for the synthesis of glycogen, but favourable for its degradation into glucose-l-phosphate which enters the pathway of glycolysis followed by the Krebs cycle (which will again raise the ATP concentration).