7.6 Enzymes

Metabolic Pathways

• Chemical changes in living organisms often happen with a number of stages. Each stage has its own specific enzyme.
• Catabolic pathways breakdown molecules.
• Anabolic pathways build up molecules.

 Linear Change Pathways (Example: Glycolysis)

• Enzyme 1 is specific only to substrate 1. It is then converted to product 1.
• Enzyme 2 is specific only to product 1 which becomes the substrate and then converted to product 2.
• Enzyme 3 is specific to product 2 which becomes the substrate and converted to product 3.
• Product is called the 'End product'.

Cyclic Pathways (Example: Krebs Cycle and Calvin Cycle)

• The initial substrate is fed into the cycle.
• Enzyme 1 combines the regenerated 'intermediate 4' with the initial substrate to catalyses the production of intermediate 1. 
• Enzyme 2 is specific to intermediate 1 and converts intermediate 1 to intermediate 2.
• Enzyme 3 is specific to intermediate 2 and catalyses it conversion to product and intermediate 3.
• Enzyme 4 is specific to intermediate 3 and catalyses its conversion to intermediate 4.
• The difference is the regeneration of the intermediate, in this case intermediate 4. 

 Induced Fit Model

•  Enzymes are very specific to certain substrates, like a lock is to a certain key.
• There is 1 enzyme for every substrate.
• The substrate induces change in a active site - the enzyme "adjusts" its structure to accommodate the substrate.

 Activation Energies

Exergonic reactions

 

 

• Enzymes lower the activation energy of the chemical reaction that they catalyse. 
• In the activated complex or transition state energy is put into the substrate to make structure weak. This allows the reaction to occur with a minimal amount of additional energy required. 
• Normal activation energy would cause damage to the proteins of the cell. So reduced activation energy make these reactions possible in a cell.
• After the product is formed, energy is released.
• Exergonic reactions release more energy than the activation energy.

Competitive and Non-Competitive Inhibitors

• Inhibitors - substances that reduce or completely stop the action of an enzyme.
• Inhibition can act on the active site (competitive) or on another region of the enzyme molecule(non-competitive). The competition in the former being for the active site of the enzyme. 

A. Competitive Inhibitors 

• The substrate and inhibitor are chemically very similar in molecular shape.
• The inhibitor can bind to the active site.
• Enzyme-inhibitor complexing blocks substrate from entering the active site. This blockage reduces the rate of reaction. 
• If the substrate concentration is increased it occupies more active sites than the inhibitor. Therefore the substrate out-competes the inhibitor for the active site.
• The rate of reaction will increase again.

Example:Succinate is converted to Fumerate by Succinate dehydrogenase(SDase).
SDase can be inhibited by a later intermediate in the cycle called malonate.

• When a competitive inhibitor is present the rate of reaction is reduced.
• Increasing the concentration of the substrate reduces the effect of the inhibitor.
• At high concentrations the substrate out-competes the inhibitory molecules for the active site. The rate of reaction therefore increases.

 B. Non-competitive Inhibitors

• The substrate and the inhibitor are chemically different in molecular structure.
• The inhibitor cannot bind to the active site, but the inhibitor can bind to another region of the enzyme molecule.
• The bonding of the inhibitor with the enzyme causes structural changes in the enzyme molecule.  
• The active site then changes shape. 
• The substrate cannot bind therefore the rate of reaction decreases.  

Example: Inhibition by metal ions (Ag⁺)
Silver ions inhibiting the formation of sulphide bridges at the amino acid cysteine.
This changes the protein bonding and in turn the active site changes excluding the substrate.

• The presence of an non-competitive inhibitor always significantly reduces the rate of reaction.  
• Increasing the concentration of the enzyme increases the chance of a collision between the substrate and an enzyme that is not inhibited already. Therefore the rate can increase.
• The rate of reaction is always lower when the inhibitor is present.

End Product Inhibition of Enzyme Pathway

• Enzyme pathways can be controlled by concentration of products from the end of the pathway.
• The principle is illustrated by the transamination (change R group) of the amino acid threonine to isoleucine. 

•  Isoleucine the end product, this molecule can inhibit the enzyme Threonine Deaminase.
• The inhibition occurs at an inhibition site on the enzyme but not the active site.
• An excess of end product (Isoleucine) switches off any more production of that product, isoleucine.
• At high concentrations, Isoleucine attaches to the inhibition site of Threonine deaminase.
• This attachment causes the active site of the enzyme to change blocking any further reaction.  
• Isoleucine is used up in cellular processes that require this particular amino acid.
• The isoleucine concentration in the cell falls and so the Isoleucine that is attached to the enzyme detaches. This amino acid is also used up in the various cellular processes.  
• With the inhibitor removed the the active site then becomes active again and the pathway switches back on. 
• The isoleucine is again in production but once high concentrations are reached the pathways is once more inhibited. The process then cycles on in alternating stages of production and inhibition.
• Notice the similarity with non-competitive inhibition.
• This mechanism makes the pathway self-regulating in terms of product manufacture.