Enzyme-mediated control of metabolic pathways

Theoretically, all enzyme reactions are reversible but the overall flux (flow) of substrate in a pathway is unidirectional. To extend our road map analogy, this type of reaction acts as a control point in a pathway, rather like a one-way street, allowing substrates to flow in only one direction. 

Such a metabolic one-way street comes about in large part due the fact that certain chemical reactions are associated with a large energy change, which in chemical terms mean that the reaction is operating far away from its true equilibrium. Reactions of this nature are difficult to reverse under the conditions of pH, temperature and substrate concentration which exist inside cells and so become physiologically irreversible . 

Reactions operating far from their equilibrium position are not easy to identify merely by looking at the metabolic map, although the involvement of ATP is often a significant clue to a reaction being irreversible. Stated simply, hydrolysis of ATP energizes a reaction which is normally irreversible. However, we can often predict the existence of 

Enzymes are proteins (gene products) synthesized by DNA transcription and messenger RNA (mRNA) translation. Many enzymes are described as being constitutive , meaning they are present at all times. Others are inducible , meaning that their synthesis can be increased on-demand when circumstances require. By increasing the concentration of certain enzymes, induction allows more substrate to undergo chemical reaction and the pathway accelerates. 

Activators and inhibitors regulate not the amount of enzyme protein but the activity ( efficiency ) of that which is present. Two principal mechanisms of control are (i) competitive and (ii) allosteric. Competitive control (inhibition) occurs when a compound which is structurally similar to the true substrate binds to the active site of the enzyme. This is how a number of drugs and poisons bring about their effect. For example, a group of therapeutic drugs called statins are used to treat heart disease because by inhibiting a key enzyme called HMGCoA reductase, they reduce the hepatic synthesis of cholesterol and therefore the plasma concentration of that lipid. 

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