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The Michaelis-Menten model describes the behavior of enzyme-driven reactions by comparing the rate of reaction (V) to the concentration of the substrate (S).  Maximal velocity (V_max) represents the speed at which the reaction occurs when the enzyme's active sites are completely saturated with substrate.  The Michaelis constant (K_m) defines the substrate concentration at which half of the enzyme's binding sites are occupied by substrate (½ V_max).  Substrates with high affinity for the enzyme typically have a low K_m.

Competitive inhibition occurs when an inhibitor binds to an enzyme and prevents it from binding the substrate.  Most competitive inhibitors (including malate) bind at the active site (substrate-binding pocket) and physically impede substrate binding.  Because these inhibitors compete with the substrate for binding to the active site, additional substrate is required to reach ½ V_max, thereby increasing apparent K_m.  Competitive inhibitors have no effect on enzyme function, and therefore V_max is unchanged.

In this example, V_max remains constant (at 400 µmol/L/sec) while K_m increases (from 8 to 16 mM) in the presence of malate.  Therefore, malate is a competitive inhibitor of succinate dehydrogenase for succinate.

(Choice A)  V_max depends on how fast an enzyme can catalyze a reaction when there are enough substrate molecules to fully saturate its active sites.  Competitive inhibitors do not affect V_max, as higher substrate concentrations are able to overcome the inhibition.

(Choice B)  Most competitive inhibitors, such as malate, bind in the substrate-binding pocket.  In contrast, most noncompetitive inhibitors bind at allosteric sites, resulting in a conformational change of the enzyme that decreases enzymatic activity and slows the rate of reaction (V_max).  Noncompetitive inhibition does not change the apparent K_m and cannot be overcome with higher substrate concentrations.

(Choice C)  Irreversible inhibitors bind to enzymes through strong covalent bonds; this typically renders the enzyme permanently ineffective, decreasing the V_max.

(Choice D)  Competitive inhibitors interfere with substrate binding due to the inhibitor's own high affinity for the enzyme's active site.  This causes the measured K_m value to increase; however, the actual enzyme affinity for the substrate remains unchanged.

Educational objective:
Competitive inhibitors compete with substrate for active binding sites on enzymes.  Additional substrate is required to achieve the same rate of reaction, increasing the measured value of the Michaelis constant (K_m).  Competitive inhibitors do not affect enzyme function; therefore, maximal velocity (V_max) is unchanged in their presence.