When an enzyme is denatured, bonds are broken, changing the enzyme's tertiary structure and causing the active site to change shape so that the substrate(s) no longer fit.

1. Temperature
2. pH 
3. Substrate concentration
4. Enzyme concentration

As temperature is increased, the rate of reaction increases until it reaches the optimum temperature.

If temperature increases past the optimum, the rate of reaction decreases until the reaction stops. 

Higher temperatures provide molecules with more kinetic energy, causing more collisions and more enzyme-substrate complexes to form. 

Temperatures higher than the optimum provide molecules with too much kinetic energy, which causes the active site to change shape and denatures the enzymes. 

An optimum temperature is the temperature at which an enzyme works fastest. 

In acidic solutions, H⁺ ions break ionic or hydrogen bonds and denature the enzymes. 

In alkaline solutions, OH^- ions break ionic or hydrogen bonds and denature the enzymes.

An enzyme's optimum pH is the pH at which it works fastest.

Increasing substrate concentration increases the rate of reaction until eventually the rate of reaction plateaus. 

Increasing substrate concentration means there are more substrate molecules available to form enzyme-substrate complexes. 

Eventually the reaction reaches a saturation point where all active sites are occupied by substrates. At this point, the enzyme concentration is a limiting factor.

Increasing enzyme concentration increases the rate of reaction until eventually the rate of reaction plateaus. 

Increasing enzyme concentration means there are more enzyme molecules available to form more enzyme-substrate complexes. 

Eventually all substrate molecules are being acted upon and substrate concentration becomes the limiting factor.