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​​​​Consider an enzymatic reaction that follows Michaelis-Menten kinetics. Let $K_{M}, S$, and $V_{\max }$ denote the Michaelis constant, substrate concentration, and maximum reaction rate, respectively. Which of the following statements is/are TRUE?

  1. For $S \ll K_{M}$, the reaction is apparent first-order in $S$.
  2. For $S \gg K_{M}$, the reaction rate is nearly independent of $S$.
  3. For $S=K_{M}$, the rate of reaction equals $V_{\max }$.
  4. $K_{M}$ is independent of the total enzyme concentration.

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